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Sample records for traumatic brain injury

  1. Using biomarkers to identify traumatic brain injury for soldiers...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Using biomarkers to identify traumatic brain injury for soldiers, sports figures Using biomarkers to identify traumatic brain injury for soldiers, sports figures A new detection ...

  2. Traumatic Brain Injury Protection: Blast Pressure Sensors in...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Find More Like This Return to Search Traumatic Brain Injury Protection: Blast Pressure ... Technology Marketing Summary The cost of treating traumatic brain injury (TBI) is ...

  3. Using biomarkers to identify traumatic brain injury for soldiers, sports

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    figures Using biomarkers to identify traumatic brain injury for soldiers, sports figures Using biomarkers to identify traumatic brain injury for soldiers, sports figures A new detection approach originally developed for tuberculosis diagnostics is being adapted as a tool for determining traumatic brain injury April 28, 2015 The LANL and SMT collaborators (left to right): Donald Shields, Aaron Anderson, Paul Smith, Nicholas Hengartner, Dr. Donald Becker, Harshini Mukundan (co-PI), Laurie

  4. Crural Artery Traumatic Injuries: Treatment with Embolization

    SciTech Connect (OSTI)

    Lopera, Jorge E. Suri, Rajeev; Cura, Marco; Kroma, Ghazwan; El-Merhi, Fadi

    2008-05-15

    The purpose of this paper is to report our experience with the endovascular treatment of crural arterial injuries using transcatheter and direct embolization techniques. A total of eight consecutive patients have been treated during a 7-year period. Six males and two females, mean age 32 years (range, 15-56 years), presented with penetrating trauma to the lower extremities. Mechanisms of injuries were stab wounds in six patients, gun shot wound in one patient, and iatrogenic injury in one patient. Five patients presented with acute trauma, while three patients presented with delayed injuries. Crural arterial injuries encountered included pseudoaneurysms with arteriovenous fistulas (n = 6), pseudoaneurysms with vessel transections (n = 2), and pseudoaneurysm (n = 1). Proximal and distal embolization with coils was used in three cases, proximal embolization with coils in three cases, percutaneous thrombin injection in one case, and liquid n-butyl cyanoacrylate in one case. Complete exclusion of the lesions was accomplished by sacrifice of one crural vessel in seven cases and of two crural vessels in one case. Two cases of delayed injuries required combined coil and liquid embolization techniques for lesion exclusion. A minor complication (groin hematoma) occurred in one patient, no distal ischemia was seen, and no amputations were required. Mean follow-up was 61 days (range, 1-180 days). One pseudoaneurysm treated with thrombin injection recurred and required surgical excision. We conclude that transcatheter embolization alone or in combination with different endovascular techniques is useful in the treatment of traumatic crural vessel injuries.

  5. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect (OSTI)

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  6. by Los Alamos National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    projects; bovine tuberculosis detection and better diagnostics for traumatic brain injury. ... Alamos medical technology company explore better diagnostics for traumatic brain injury. ...

  7. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    biomarkers to identify traumatic brain injury for soldiers, sports figures April 28, 2015 ... as a tool for determining traumatic brain injury, one of the challenges facing the ...

  8. New Mexico small businesses helped by Los Alamos National Laboratory...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    projects; bovine tuberculosis detection and better diagnostics for traumatic brain injury. ... Alamos medical technology company explore better diagnostics for traumatic brain injury. ...

  9. ASCeNews Quarterly Newsletter - March/June 2011 | National Nuclear...

    National Nuclear Security Administration (NNSA)

    ... LLNL Researchers Find Way to Mitigate Traumatic Brain Injury in Study for Joint IED Defeat ... reduce the severity of traumatic brain injury (TBI) from blunt and ballistic impacts. ...

  10. Helmets Designed by Supercomputers Help Warfighters at Home

    Broader source: Energy.gov [DOE]

    These supercomputing applications are helping protect warfighters from the blast waves produced by explosions that cause traumatic brain injury (TBI).

  11. HEAD INJURY ASSESSMENT IN JUVENILE CHINOOK USING THE ALPHA II-SPECTRIN BIOMARKER: EFFECTS OF PRESSURE CHANGES AND PASSAGE THROUGH A REMOVABLE SPILLWAY WEIR

    SciTech Connect (OSTI)

    Jonason, C.; Miracle, A.

    2009-01-01

    The cytoskeletal protein alpha II-spectrin has specifi c neurodegenerative mechanisms that allow the necrotic (injury-induced) and apoptotic (non-injury-induced) pathways of proteolysis to be differentiated in an immunoblot. Consequently, ?II-spectrin breakdown products (SBDPs) are potential biomarkers for diagnosing traumatic brain injury (TBI). The purpose of the following investigation, consisting of two studies, was to evaluate the utility of the spectrin biomarker in diagnosing TBI in fi sh that travel through hydroelectric dams in the Columbia and Snake Rivers. The fi rst study used hyperbaric pressure chambers to simulate the pressure changes that affect fi sh during passage through a Federal Columbia River Power System (FCRPS) Kaplan turbine. The second study tested the effect of a removable spillway weir (RSW) on the passage of juvenile chinook (Oncorhynchus tshawytscha). This study was conducted in tandem with a balloon-tag study by the U.S. Army Corps of Engineers. Brain samples from fi sh were collected and analyzed using an immunoblot for SBDPs, and imaging software was used to quantify the protein band density and determine the ratio of cleaved protein to total protein. The biomarker analyses found higher SBDP expression levels in fi sh that were exposed to lower pressure nadirs and fi sh that passed through the RSW at a deep orientation. In general, the incidence of injuries observed after treatment positively correlated with expression levels, suggesting that the biomarker method of analysis is comparable to traditional methods of injury assessment. It was also found that, for some treatments, the 110 kDa spectrin fragment (SBDP 110) correlated more strongly with necrotic head injury incidence and mortality rates than did the total cleaved protein or the 120 kDa fragment. These studies will be informative in future decisions regarding the design of turbines and fi sh passage structures in hydroelectric dams and will hopefully contribute to the development of faster and more accurate techniques for diagnosing TBI in fi sh.

  12. S A N D I A M I S S I O N

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Investigation of Blast-induced Traumatic Brain Injury ......simulations of blast waves on the brain with clinical studies of vet- erans ...

  13. April

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    brain injury for soldiers, sports figures A new detection approach originally developed for tuberculosis diagnostics is being adapted as a tool for determining traumatic brain ...

  14. Optical spectroscopy for the detection of ischemic tissue injury

    DOE Patents [OSTI]

    Demos, Stavros (Livermore, CA); Fitzgerald, Jason (Sacramento, CA); Troppmann, Christoph (Sacramento, CA); Michalopoulou, Andromachi (Athens, GR)

    2009-09-08

    An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient's body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

  15. New research, publications and videos

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Sara Del Valle said. Using biomarkers to identify traumatic brain injury for soldiers, sports figures A new detection approach originally developed for tuberculosis diagnostics is...

  16. donations

    National Nuclear Security Administration (NNSA)

    Sheely Foundation. On Aug. 22, 2011, Derek suffered atraumatic brain injuryduring football practice at Frostburg State University and died one week...

  17. Endovascular Management of Extra-cranial Supra-aortic Vascular Injuries

    SciTech Connect (OSTI)

    Almazedi, Bahir Lyall, Harpreet; Bhatnagar, Priya; Kessel, David; McPherson, Simon; Patel, Jai V.; Puppala, Sapna

    2013-02-08

    Supra-aortic vessel injuries are uncommon but can be life-threatening and surgically challenging. Trauma to these vessels may be blunt or penetrating, including iatrogenic trauma following the insertion of central venous lines, which may be preventable. Recent advances in technology have resulted in endovascular therapy becoming a common first-line treatment,and interventional radiologists now play a major role in the management of these vascular injuries. We review the literature on the endovascular management of these types of injuries and describe a spectrum of case-based extra-cranial supra-aortic vascular injuries managed at our institution and the range of imaging appearances, including active contrast extravasation, traumatic vessel occlusion, true aneurysms, pseudoaneurysms, and arteriovenous fistulae.

  18. TH-A-18C-09: Ultra-Fast Monte Carlo Simulation for Cone Beam CT Imaging of Brain Trauma

    SciTech Connect (OSTI)

    Sisniega, A; Zbijewski, W; Stayman, J; Yorkston, J; Aygun, N; Koliatsos, V; Siewerdsen, J

    2014-06-15

    Purpose: Application of cone-beam CT (CBCT) to low-contrast soft tissue imaging, such as in detection of traumatic brain injury, is challenged by high levels of scatter. A fast, accurate scatter correction method based on Monte Carlo (MC) estimation is developed for application in high-quality CBCT imaging of acute brain injury. Methods: The correction involves MC scatter estimation executed on an NVIDIA GTX 780 GPU (MC-GPU), with baseline simulation speed of ~1e7 photons/sec. MC-GPU is accelerated by a novel, GPU-optimized implementation of variance reduction (VR) techniques (forced detection and photon splitting). The number of simulated tracks and projections is reduced for additional speed-up. Residual noise is removed and the missing scatter projections are estimated via kernel smoothing (KS) in projection plane and across gantry angles. The method is assessed using CBCT images of a head phantom presenting a realistic simulation of fresh intracranial hemorrhage (100 kVp, 180 mAs, 720 projections, source-detector distance 700 mm, source-axis distance 480 mm). Results: For a fixed run-time of ~1 sec/projection, GPU-optimized VR reduces the noise in MC-GPU scatter estimates by a factor of 4. For scatter correction, MC-GPU with VR is executed with 4-fold angular downsampling and 1e5 photons/projection, yielding 3.5 minute run-time per scan, and de-noised with optimized KS. Corrected CBCT images demonstrate uniformity improvement of 18 HU and contrast improvement of 26 HU compared to no correction, and a 52% increase in contrast-tonoise ratio in simulated hemorrhage compared to “oracle” constant fraction correction. Conclusion: Acceleration of MC-GPU achieved through GPU-optimized variance reduction and kernel smoothing yields an efficient (<5 min/scan) and accurate scatter correction that does not rely on additional hardware or simplifying assumptions about the scatter distribution. The method is undergoing implementation in a novel CBCT dedicated to brain trauma imaging at the point of care in sports and military applications. Research grant from Carestream Health. JY is an employee of Carestream Health.

  19. 2012 CFCNCA Catalog of Caring

    Energy Savers [EERE]

    ... as autism, down syndrome, and traumatic brain injury. 0.0% N,O,P 49943 Baltimore Art & ... helps children with disorders of the brain, spinal cord, and musculoskeletal system ...

  20. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    biomarkers to identify traumatic brain injury for soldiers, sports figures April 28, 2015 Los Alamos and partners identify clues through body chemistry LOS ALAMOS, N.M., April 28, 2015-A new detection approach originally developed for tuberculosis diagnostics is being adapted as a tool for determining traumatic brain injury, one of the challenges facing the medical community as it works to treat military and sports figures with head injuries. Minute chemical alterations in the body, called

  1. Illness and Injury Surveillance Program (IISP) Reports

    Broader source: Energy.gov [DOE]

    A full list of Special Illness and Injury Surveillance and Annual Reports are available upon request.

  2. Refinery, petrochemical plant injuries decline

    SciTech Connect (OSTI)

    Not Available

    1994-07-25

    The National Petroleum Refiners Association (NPRA) reports a 7% reduction in workplace injury and illness incidence rates for refineries in 1993, and a 21% decrease for petrochemical plants. The report summarizes data from 135 of the 162 US member refineries, and 117 of the 172 US member petrochemical plants. This paper summarizes the report findings.

  3. Ergonomics research: Impact on injuries

    SciTech Connect (OSTI)

    Heller, A.

    1997-03-01

    No tool has characterized the modern workplace like the personal computer. An estimated 60 million PCs adorn desks in virtually every work environment today, achieving remarkable increases in productivity while virtually transforming entire industries. At the same time, however, an increasing number of employees are heavy computer users who suffer painful and sometimes debilitating (and occasionally career-ending) injuries called work-related musculoskeletal disorders (WRMSDs) involving their hands and arms. Within computer-intensive occupations the incidence of injury has doubled every year for the past four years. These disorders cost the nation over $40 billion per year in medical costs alone. When productivity losses and disability and retraining costs are included, the total bill may top $80 billion per year. A common injury is tendonitis--inflammation of tendons, which connect muscle to bone. Another well-publicized injury, carpal tunnel syndrome, involves damage to the median nerve that travels through a tight space in the wrist called the carpal tunnel. In the past, safety at most work sites, including Lawrence Livermore, traditionally focused on avoiding accidental injuries caused by hazardous materials or industrial equipment. As a result, procedures and instruments were developed that can detect, for example, toxic solvents at extremely low levels. Little is known about the range of WRMSDs which can lend itself to avoiding these problems. In response to the lack of scientific data, Lawrence Livermore`s Interdisciplinary Ergonomics Research Program is addressing comprehensively the problem of WRMSDs plaguing US industry. The program uses a multidisciplinary research team that taps LLNL`s strengths in human factors design and engineering, computational modeling, biomechanical engineering, sensors, industrial hygiene, and occupational medicine.

  4. Portable MRI

    SciTech Connect (OSTI)

    Espy, Michelle A.

    2012-06-29

    This project proposes to: (1) provide the power of MRI to situations where it presently isn't available; (2) perform the engineering required to move from lab to a functional prototype; and (3) leverage significant existing infrastructure and capability in ultra-low field MRI. The reasons for doing this: (1) MRI is the most powerful tool for imaging soft-tissue (e.g. brain); (2) Billions don't have access due to cost or safety issues; (3) metal will heat/move in high magnetic fields; (4) Millions of cases of traumatic brain injury in US alone; (5) even more of non-traumatic brain injury; (6) (e.g. stroke, infection, chemical exposure); (7) Need for early diagnostic; (8) 'Signature' wound of recent conflicts; (9) 22% of injuries; (10) Implications for post-traumatic stress disorder; and (11) chronic traumatic encephalopathy.

  5. 414th Brookhaven Lecture

    SciTech Connect (OSTI)

    Anat Biegon

    2006-04-19

    "Of Boys and Girls and Bumps on the Head." Although it has been well documented that gender affects the prevalence of disorders such as depression and Attention deficit-hyperactivity disorder, recent head injury trials suggest that both age and sex affect the likelihood and degree of recovery from injuries to the brain. While girls are more likely to die following a traumatic brain injury than boys, that result is reversed after the age of 50, when men die twice as often.

  6. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    SciTech Connect (OSTI)

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  7. PIA - Richland Occupational Injury and Illness | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Injury and Illness PIA - Richland Occupational Injury and Illness PIA - Richland Occupational Injury and Illness PDF icon PIA - Richland Occupational Injury and Illness More Documents & Publications Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory PIA - Bonneville Power Adminstration Ethics Helpline

  8. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect (OSTI)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  9. Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

    SciTech Connect (OSTI)

    Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2014-09-15

    Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation. These results suggest that another role for the iNOS/Akt pathway may be involved in neuronal survival or plasticity by magnolol after ischemic injury. - Highlights: • Magnolol attenuates brain damage in ischemic rats. • Effects of magnolol on stroke animals in ROS and acute inflammation cytokines. • Oxidants and Akt/NF-κB signaling are involved in the neuroprotection of magnolol.

  10. Methods for assisting recovery of damaged brain and spinal cord using arrays of X-ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; McDonald, III, John W.

    2007-01-02

    A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

  11. Methods for assisting recovery of damaged brain and spinal cord using arrays of X-Ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; McDonald, III, John W.

    2007-12-04

    A method of assisting recovery of an injury site of brain or spinal cord injury includes providing a therapeutic dose of X-ray radiation to the injury site through an array of parallel microplanar beams. The dose at least temporarily removes regeneration inhibitors from the irradiated regions. Substantially unirradiated cells surviving between the microplanar beams migrate to the in-beam irradiated portion and assist in recovery. The dose may be administered in dose fractions over several sessions, separated in time, using angle-variable intersecting microbeam arrays (AVIMA). Additional doses may be administered by varying the orientation of the microplanar beams. The method may be enhanced by injecting stem cells into the injury site.

  12. Rapid brain scanning radiopharmaceutical

    DOE Patents [OSTI]

    Sargent, T.W. III; Shulgin, A.T.; Mathis, C.A.

    1987-03-03

    A method for detecting the blood flow in animals, particularly in the brain, is provided wherein a detectable amount of a novel radioactive compound of the formula 1 is administered to one animal: as given in figure in patent wherein R[sub 1] and R[sub 2] are independently alkyl of 1 to 6 carbon atoms or benzyl; R[sub 3] is alkyl of 1 to 6 carbon atoms, benzyl, cyclopropylalkyl of 4 to 6 carbon atoms, or cyanoalkyl of 2 to 6 carbon atoms; R[sub 4] is hydrogen, benzyl or alkyl of 1 to 6 carbon atoms; with the provisos that R[sub 4] is not isopropyl and when R[sub 4] is methyl, R[sub 3] is not benzyl; and X is a radioactive halogen. 2 figs.

  13. Rapid brain scanning radiopharmaceutical

    DOE Patents [OSTI]

    Sargent, III, Thornton W.; Shulgin, Alexander T.; Mathis, Chester A.

    1987-01-01

    A method for detecting the blood flow in animals, particularly in the brain, is provided wherein a detectable amount of a novel radioactive compound of the formula I is administered to one animal: ##STR1## wherein R.sub.1 and R.sub.2 are independently alkyl of 1 to 6 carbon atoms or benzyl; R.sub.3 is alkyl of 1 to 6 carbon atoms, benzyl, cyclopropylalkyl of 4 to 6 carbon atoms, or cyanoalkyl of 2 to 6 carbon atoms; R.sub.4 is hydrogen, benzyl or alkyl of 1 to 6 carbon atoms; with the provisos that R.sub.4 is not isopropyl and when R.sub.4 is methyl, R.sub.3 is not benzyl; and X is a radioactive halogen.

  14. Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

    SciTech Connect (OSTI)

    Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan; Brat, Daniel J.; Shu, Hui-Kuo; Olson, Jeffrey J.

    2011-11-15

    Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resection margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.

  15. Solar Brain Srl | Open Energy Information

    Open Energy Info (EERE)

    Brain Srl Jump to: navigation, search Name: Solar Brain Srl Place: Rome, Italy Zip: 189 Sector: Solar Product: Rome-based solar and alternative energy company. References: Solar...

  16. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in ... diseases affecting the brain and its ability to make new connections and recall memories. ...

  17. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Brain Receptor Structures Key to Future Therapeutics Print Wednesday, 28 January 2015 00:00 With an aging population in ...

  18. Injury experience in coal mining, 1990

    SciTech Connect (OSTI)

    1991-01-01

    This Mine Safety and Health Administration (MSHA) informational report reviews in detail the occupational injury and illness experience of coal mining in the United States for 1990. Data reported by operators of mining establishments concerning work injuries are summarized by work location, accident classification, part of body injured, nature of injury, occupation, and anthracite or bituminous coal. Related information on employment, worktime, and operating activity also is presented. Data reported by independent contractors performing certain work at mining locations are depicted separately in this report. For ease of comparison between coal mining and the metal and nonmetal mineral mining industries, summary reference tabulations are included at the end of both the operator and the contractor sections of this report.

  19. Analysis of brain patterns using temporal measures

    SciTech Connect (OSTI)

    Georgopoulos, Apostolos

    2015-08-11

    A set of brain data representing a time series of neurophysiologic activity acquired by spatially distributed sensors arranged to detect neural signaling of a brain (such as by the use of magnetoencephalography) is obtained. The set of brain data is processed to obtain a dynamic brain model based on a set of statistically-independent temporal measures, such as partial cross correlations, among groupings of different time series within the set of brain data. The dynamic brain model represents interactions between neural populations of the brain occurring close in time, such as with zero lag, for example. The dynamic brain model can be analyzed to obtain the neurophysiologic assessment of the brain. Data processing techniques may be used to assess structural or neurochemical brain pathologies.

  20. Lung injury in dimethyl sulfate poisoning

    SciTech Connect (OSTI)

    Ip, M.; Wong, K.L.; Wong, K.F.; So, S.Y.

    1989-02-01

    Two manual laborers were exposed to dimethyl sulfate during work and sustained mucosal injury to the eyes and respiratory tract. In one of them, noncardiogenic pulmonary edema occurred and improved with high-dose methylprednisolone. On follow-up for 10 months, this patient developed persistent productive cough with no evidence of bronchiectasis or bronchial hyperreactivity.

  1. Operation Greenhouse. Scientific Director's report of atomic weapon tests at Eniwetok, 1951. Annex 2. 9. Blast injuries in foxholes

    SciTech Connect (OSTI)

    Talbot, J.M.; Maupin, C.S.

    1985-04-01

    This experiment was conducted to gain information about the amount of protection from direct blast effects that may be provided by foxholes of uniform dimensions located within distances of a nuclear explosion that are recognized as lethal for combinations of thermal and ionzing radiations and indirect blast injuries. Sixteen dogs protected in foxholes were exposed in pairs to the nuclear detonation. Autopsies performed between 10 and 15 hours after the blast demonstrated mild to moderately severe lung hemorrhages and three instances of mild to moderately severe brain hemorrhage. Ruptured ear drums and blast damage to abdominal viscera were infrequent. Evidences of acute ionizing radiation injury consisted in decreases in absolute lymphocyte counts and changes in lymph nodes and spleens. Photographs and diagrams of foxholes, animals, and tissue speciments; graphs of blast pressures, gamma doses, and neutron fluxes are included.

  2. BrainMap `95 workshop

    SciTech Connect (OSTI)

    1995-12-31

    The fourth annual BrainMap workshop was held at La Mansion del Rio Hotel in San Antonio December 3--4, 1995. The conference title was ``Human Brain Mapping and Modeling.`` The meeting was attended by 137 registered participants and 30 observers from 82 institutions representing 12 countries. The meeting focused on the technical issues associated with brain mapping and modeling. A total of 23 papers were presented covering the following topics: spatial normalization and registration; functional image analysis; metanalysis and modeling; and new horizons in biological databases. The full program with abstracts was available on the Research Imaging Center`s web site. A book will be published by John Wiley and Sons prior to the end of 1998.

  3. Late Pseudocoarctation Syndrome After Stent-Graft Implantation For Traumatic Aortic Rupture

    SciTech Connect (OSTI)

    Letocart, Vincent Fau, Georges Tirouvanziam, Ashok; Toquet, Claire; Al Habash, Oussama Guerin, Patrice; Rousseau, Herve; Crochet, Dominique

    2013-06-15

    The present observation illustrates an unusual complication occurring after stent-grafting (S-graft) for aortic isthmus rupture. A 22-year-old patient, treated by S-graft in the emergency department for traumatic aortic rupture, was readmitted 10 months later with pseudocoarctation syndrome. A membrane was found inside the stent-graft that had induced a pseudo-dissection, which caused the pseudocoarctation syndrome. Surgical treatment consisted of removing the stent-graft and membrane and replacing it with a vascular implant. The patient's clinical course was fair. The suggested mechanism was circumferential neoendothelialization of the stent-graft. Dehiscence caused the superior part of the membrane to drop into the lumen of the stent-graft creating a 'false channel' that compressed the 'true lumen' and induced 'pseudocoarctation' syndrome. The cause of the extensive neointimalization remains unexplained. Thoracic aortic stent-grafts require regular follow-up monitoring by angioscan or angio-magnetic resonance imaging.

  4. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Print A team of scientists from the Howard Hughes ... a fluorescent protein (CaMPARI) that allows the permanent marking of active brain cells. ...

  5. 6.20 Mapping Human Brain Function

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    0 612011 6.20 Mapping Human Brain Function Many mysteries of the human brain have been unraveled by positron emission tomography (PET), an imaging tool used worldwide to diagnose ...

  6. The Brain: Key To a Better Computer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain: Key To a Better Computer - Sandia Energy Energy Search Icon Sandia Home Locations ... Twitter Google + Vimeo GovDelivery SlideShare The Brain: Key To a Better Computer Home...

  7. COLLOQUIUM: Your Restless Brain: Changing Continually Throughout...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain: Changing Continually Throughout the Day and Night Professor Barry Jacobs Princeton University Presentation: File WC02APR2014BJacob.pptx As you read this, your brain is ...

  8. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity A Designed Protein Maps Brain Activity Print Wednesday, 28 October 2015 00:00 A team of scientists from the Howard Hughes Medical Institute's ...

  9. Scientists examine proton radiography of brain mockup

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Proton Radiography Of Brain Mockup Scientists examine proton radiography of brain mockup The use of such a high-energy proton beam is ideal for imaging small tumors within patients ...

  10. Visualizing Brain Metals in Health and Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Visualizing Brain Metals in Health and Disease figure 1 Fig. 1. Rapid-scanning x-ray ... The beam intensity was monitored with a N2-filled ion chamber (I0). The brain slice was ...

  11. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Brain Receptor Structures Key to Future Therapeutics Print Wednesday, 28 January 2015 00:00 With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases affecting the brain and its ability to make new connections and recall memories. Some of the most important players in the brain's normal function are the glutamate receptors, which are involved in nervous-system development and function.

  12. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Print A team of scientists from the Howard Hughes Medical Institute's Janelia Research Campus designed and validated via x-ray crystallographic studies a fluorescent protein (CaMPARI) that allows the permanent marking of active brain cells. The protein was then used to study live changes via fluorescence in the active nerve cells in brains of fruit flies, zebrafish, and mice. The Neural Basis of Behavior Signals in our brains are propagated with voltage and

  13. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Print A team of scientists from the Howard Hughes Medical Institute's Janelia Research Campus designed and validated via x-ray crystallographic studies a fluorescent protein (CaMPARI) that allows the permanent marking of active brain cells. The protein was then used to study live changes via fluorescence in the active nerve cells in brains of fruit flies, zebrafish, and mice. The Neural Basis of Behavior Signals in our brains are propagated with voltage and

  14. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Print A team of scientists from the Howard Hughes Medical Institute's Janelia Research Campus designed and validated via x-ray crystallographic studies a fluorescent protein (CaMPARI) that allows the permanent marking of active brain cells. The protein was then used to study live changes via fluorescence in the active nerve cells in brains of fruit flies, zebrafish, and mice. The Neural Basis of Behavior Signals in our brains are propagated with voltage and

  15. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity A Designed Protein Maps Brain Activity Print Wednesday, 28 October 2015 00:00 A team of scientists from the Howard Hughes Medical Institute's Janelia Research Campus designed and validated via x-ray crystallographic studies a fluorescent protein (CaMPARI) that allows the permanent marking of active brain cells. The protein was then used to study live changes via fluorescence in the active nerve cells in brains of fruit flies, zebrafish, and mice. The Neural

  16. Injury and Illness Reporting Guide | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Injury and Illness Reporting Guide Injury and Illness Reporting Guide August 16, 2012 DOE Order 231.1B, Environment, Safety and Health Reporting Order establishes requirements to ensure timely and accurate information about events that have or could impact worker, the environment, operations or the public. The Injury and Illness Reporting Guide is referenced in DOE Order 231.1B as a resource for supplemental information needed to facilitate uniform data reporting for events resulting in worker

  17. 2010 Idaho National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-09-26

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  18. 2010 Argonne National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-06-20

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  19. 2010 Hanford Site Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-10-05

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  20. 2010 Savannah River Site Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-09-12

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  1. 2010 Pantex Plant Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-06-29

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  2. 2010 Brookhaven National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-08-16

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  3. 2010 Kansas City Plant Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-06-20

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  4. 2010 Sandia National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-10-26

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  5. Injury and Illness Reporting Guide | Department of Energy

    Office of Environmental Management (EM)

    Injury and Illness Reporting Guide Injury and Illness Reporting Guide August 16, 2012 DOE Order 231.1B, Environment, Safety and Health Reporting Order establishes requirements to ensure timely and accurate information about events that have or could impact worker, the environment, operations or the public. The Injury and Illness Reporting Guide is referenced in DOE Order 231.1B as a resource for supplemental information needed to facilitate uniform data reporting for events resulting in worker

  6. Work-Related Injuries and Illnesses | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    All work-related injuries and illnesses must be reported to the Occupational Medicine office and to the employee's supervisor as soon as possible, even if no medical...

  7. Illness and Injury Surveillance Program Guidelines

    Office of Environmental Management (EM)

    DOE-STD-1190-2007 DOE STANDARD ILLNESS AND INJURY SURVEILLANCE PROGRAM GUIDELINES U.S. Department of Energy AREA OCSH Washington, D.C. 20585 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. NOT MEASUREMENT SENSITIVE DOE-STD-1190-2007 Available on the Department of Energy Technical Standards Program Web site at http://tis.eh.doe.gov/techstds/ DOE-STD-1190-2007 Foreword 1. Use of this standard is not mandatory. Users should review the document and determine if it

  8. Type A Investigation of the Electrical Arc Injury at the Stanford...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of the Electrical Arc Injury at the Stanford Linear Accelerator Complex on October 11, 2004 Type A Investigation of the Electrical Arc Injury at the Stanford Linear Accelerator...

  9. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases affecting the brain and its ability to make new connections and recall memories. Some of the most important players in the brain's normal function are the glutamate receptors, which are involved in nervous-system development and function. These molecules transmit signals between nerve cells and are critical to learning and

  10. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases affecting the brain and its ability to make new connections and recall memories. Some of the most important players in the brain's normal function are the glutamate receptors, which are involved in nervous-system development and function. These molecules transmit signals between nerve cells and are critical to learning and

  11. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases affecting the brain and its ability to make new connections and recall memories. Some of the most important players in the brain's normal function are the glutamate receptors, which are involved in nervous-system development and function. These molecules transmit signals between nerve cells and are critical to learning and

  12. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases affecting the brain and its ability to make new connections and recall memories. Some of the most important players in the brain's normal function are the glutamate receptors, which are involved in nervous-system development and function. These molecules transmit signals between nerve cells and are critical to learning and

  13. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Print A team of scientists from the Howard Hughes Medical Institute's Janelia Research Campus designed and validated via x-ray...

  14. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases...

  15. Of Boys and girls and Bumps on the Head (414th Brookhaven Lecture)

    SciTech Connect (OSTI)

    Biegon, Anat

    2006-04-19

    If you are a young man driving your wife and her parents, be very careful. If you are involved in a serious car accident, you and your mother-in-law are most likely to survive. This 'warning' is one conclusion of Anat Biegon's upcoming 414th Brookhaven Lecture, entitled 'Of Boys and Girls and Bumps on the Head.' Joanna Fowler of the Chemistry Department, Director of BNL's Translational Neuroimaging Center, will introduce the lecturer. Biegon, a senior medical scientist in the Medical Department, will detail how research has refined scientists view of gender differences in the prevalence and outcome of diseases affecting the brain. Although it has been well documented that gender affects the prevalence of disorders such as depression and Attention deficit-hyperactivity disorder, recent head injury trials suggest that both age and sex affect the likelihood and degree of recovery from injuries to the brain. While girls are more likely to die following a traumatic brain injury than boys, that result is reversed after the age of 50, when men die twice as often. Although it has been well documented that gender affects the prevalence of disorders such as depression and Attention deficit-hyperactivity disorder, recent head injury trials suggest that both age and sex affect the likelihood and degree of recovery from injuries to the brain. While girls are more likely to die following a traumatic brain injury than boys, that result is reversed after the age of 50, when men die twice as often.

  16. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

    SciTech Connect (OSTI)

    Alvarado, M.; Biegon, A.

    2001-01-01

    The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.

  17. Investigation of injury data at a detonator facility

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Cournoyer, Michael E.; Apodaca, Marylou; Bustamante, Robert A.; Armijo, Mark A.; Lawton, Cindy M.

    2015-08-28

    This paper focuses on the collection of injury data; incorporation of this information into a visual format that DET management uses to make decisions to improving operations. Results from this 1 study include of the following: chemical exposure cases have declined because the Hazard Assessment of each DET operation has been formally reviewed; Slip/Trip/Fall factors have decreased due to Slip Simulator training; and work station evaluations have led to fewer injuries with Lift/Push/Pull factors. Rotation of employees, ergonomically friendly balances, automatic powder dispensers, and other equipment procurements will lower ergonomic injuries.

  18. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    SciTech Connect (OSTI)

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in CBF. • Administration of methamphetamine may lead to hypoxic insult.

  19. System Provides Clear Brain Scans of Awake, Unrestrained Mice...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    System Provides Clear Brain Scans of Awake, Unrestrained Mice dynamic imaging of mice ... obtain detailed, functional images of the brain of a conscious mouse as it moves around. ...

  20. Other: Multiscale Simulation of Blood Flow in Brain Arteries...

    Office of Scientific and Technical Information (OSTI)

    Other: Multiscale Simulation of Blood Flow in Brain Arteries with an Aneurysm Citation Details Title: Multiscale Simulation of Blood Flow in Brain Arteries with an Aneurysm

  1. Brain teasers traveling exhibit opens at Los Alamos National...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain teasers exhibit opens at museum Brain Teasers traveling exhibit opens at Los Alamos National Laboratory's Bradbury Science Museum The interactive exhibit is a collection of ...

  2. Final Report on LDRD project 130784 : functional brain imaging...

    Office of Scientific and Technical Information (OSTI)

    brain imaging by tunable multi-spectral Event-Related Optical Signal (EROS). Citation Details In-Document Search Title: Final Report on LDRD project 130784 : functional brain ...

  3. Consciousness and the Social Brain | Princeton Plasma Physics...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    MBG Auditorium Consciousness and the Social Brain Professor Michael Graziano, Department ... Science on Saturday, January 10, 2015, "Consciousness and The Social Brain", Professor ...

  4. Type B Accident Investigation Of The February 25, 2009 Injury...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    New Mexico Type B Accident Investigation Of The February 25, 2009 Injury To A Passenger In An Electric Cart At The Waste Isolation Pilot Plant, Carlsbad, New Mexico April 1, ...

  5. Type B Accident Investigation Board Report on the Head Injury...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    New Mexico - August 25, 2004 Type B Accident Investigation Board Report on the Head Injury to a Miner at the Waste Isolation Pilot Plant, Carlsbad, New Mexico - August 25, ...

  6. Loss of Situational Awareness Results in Worker Injury | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Loss of Situational Awareness Results in Worker Injury Last week, as a worker was descending a stepladder, the worker slipped on the last rung of the ladder. The worker reacted by tightening their grip on the handle they were using to steady their descent. Their shoulder temporarily and suddenly supported their body weight, resulting in an injury to that shoulder. We can point to a number of events over the past few years that occurred because the worker lost focus of their situational

  7. 2009 Pantex Plant Annual Illness and Injury Surveillance

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Security, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2010-12-15

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  8. 2009 Hanford Site Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Security, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2010-12-01

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  9. 2009 Argonne National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Security, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2010-08-19

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  10. 2009 Brookhaven National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Security, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2010-11-24

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  11. 2008 Idaho National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Security, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2010-11-23

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  12. SU-E-QI-12: Morphometry Based Measurements of the Structural Response to Whole Brain Radiation

    SciTech Connect (OSTI)

    Fuentes, D; Castillo, R; Castillo, E; Guerrero, T

    2014-06-15

    Purpose: Although state of the art radiation therapy techniques for treating intracranial malignancies have eliminated acute brain injury, cognitive impairment occurs in 50–90% of patients who survive >6mo post irradiation. Quantitative characterization of therapy response is needed to facilitate therapeutic strategies to minimize radiation induced cognitive impairment [1]. Deformation based morphometry techniques [2, 3] are presented as a quantitative imaging biomarker of therapy response in patients receiving whole brain radiation for treating medulloblastoma. Methods: Post-irradiation magnetic resonance imaging (MRI) data sets were retrospectively analyzed in N=15 patients, >60 MR image datasets. As seen in Fig 1(a), volume changes at multiple time points post-irradiation were quantitatively measured in the cerebrum and ventricles with respect to pre-irradiation MRI. A high resolution image Template, was registered to the pre-irradiation MRI of each patient to create a brain atlas for the cerebrum, cerebellum, and ventricles. Skull stripped images for each patient were registered to the initial pre-treatment scan. Average volume changes in the labeled regions were measured using the determinant of the displacement field Jacobian. Results: Longitudinal measurements, Fig 1(b-c), show a negative correlation p=.06, of the cerebral volume change with the time interval from irradiation. A corresponding positive correlation, p=.01, between ventricular volume change and time interval from irradiation is seen. One sample t-test for correlations were computed using a Spearman method. An average decrease in cerebral volume, p=.08, and increase in ventricular volume, p<.001, was observed. The radiation dose was seen directly proportional to the induced volume changes in the cerebrum, r=−.44, p<.001, Fig 1(d). Conclusion: Results indicate that morphometric monitoring of brain tissue volume changes may potentially be used to quantitatively assess toxicity and response to radiation and may provide insight in developing new therapeutic approaches and monitoring efficacy.

  13. miRNAs in brain development

    SciTech Connect (OSTI)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.

  14. OSS 19.11 Injury and Illness Record Keeping 9/19/03 | Department of Energy

    Energy Savers [EERE]

    1 Injury and Illness Record Keeping 9/19/03 OSS 19.11 Injury and Illness Record Keeping 9/19/03 The objective of this surveillance is to evaluate the contractor's process for identifying and recording data pertaining to occupational injuries and illnesses. The Facility Representative will benchmark the existing records regarding injuries and illnesses, against the source data maintained by individual field medical facilities. In addition, the Facility Representative will evaluate the

  15. Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    | Department of Energy Injury & Illness System (01&15) PIA, Idaho National Laboratory Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory PDF icon Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory More Documents & Publications Energy Employees' Occupational Illness Compensation Program Act (EEOICPA) Tracking Database, INL Energy

  16. Scientists examine proton radiography of brain mockup

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Proton Radiography Of Brain Mockup Scientists examine proton radiography of brain mockup The use of such a high-energy proton beam is ideal for imaging small tumors within patients for targeted proton therapy. March 25, 2013 Proton radiograph of a high-fidelity mockup of a human head Proton radiograph of a high-fidelity mockup of a human head. Proton radiography, which was invented at Los Alamos, employs a high-energy proton beam to image the properties and behavior of materials. Los Alamos

  17. Electromagnetic imaging of dynamic brain activity

    SciTech Connect (OSTI)

    Mosher, J.; Leahy, R.; Lewis, P.; Lewine, J.; George, J.; Singh, M.

    1991-12-31

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  18. Operating Experience Level 3, Injuries: Recent Trend in Musculoskeletal Disorders

    Broader source: Energy.gov [DOE]

    OE-3 2016-03: This Operating Experience Level 3 (OE-3) document provides information that workers at Department of Energy (DOE) facilities can use to reduce the risk of musculoskeletal disorders (MSDs) and injuries. In addition, planners may find useful information for developing work packages that consider ergonomic principles.

  19. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect (OSTI)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ? Acetaminophen-induced liver injury is a significant clinical challenge. ? HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ? We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  20. High-Tech Brain Implant Predicts, Prevents Epileptic Seizures...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    High-Tech Brain Implant Predicts, Prevents Epileptic Seizures (ANL-IN-08-043) Argonne ... an advanced brain implant system that finds and stops seizures before they happen. ...

  1. BigNeuron: Unlocking the Secrets of the Human Brain

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    BigNeuron: Unlocking the Secrets of the Human Brain BigNeuron: Unlocking the Secrets of the Human Brain Berkeley Researchers and Supercomputers to Help Create a Standard 3D Neuron ...

  2. Take a Closer Look at the Brain | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Take a Closer Look at the Brain Click to email this to a friend (Opens in new window) ... Take a Closer Look at the Brain Worldwide, more than 450 million people are living with ...

  3. Scientists model brain structure to help computers recognize...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Do you see what I see? Scientists model brain structure to help computers recognize ... Introspectively, we know that the human brain solves this problem very well. We only have ...

  4. BigNeuron: Unlocking the Secrets of the Human Brain

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    BigNeuron: Unlocking the Secrets of the Human Brain BigNeuron: Unlocking the Secrets of the Human Brain Berkeley Researchers and Supercomputers to Help Create a Standard 3D Neuron Model March 31, 2015 Linda Vu, +1 510 495 2402, lvu@lbl.gov n11.jpg Neuron Image courtesy of The Allen Institute for Brain Science Before scientists can unlock the secrets of the human brain, they must fully understand neurons-the cells of our brain, spinal cord and overall nervous system. Thousands of detailed neuron

  5. Spinal Injury: Regeneration, Recovery, and a Possible New Approach

    ScienceCinema (OSTI)

    Cohen, Avis [University of Maryland, College Park, Maryland, United States

    2010-01-08

    Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficulties heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.

  6. Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

    SciTech Connect (OSTI)

    Rades, Dirk; Evers, Jasmin N.; Veninga, Theo; Stalpers, Lukas J.A.; Lohynska, Radka; Schild, Steven E.

    2011-11-15

    Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 4 Gy in elderly patients ({>=}65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 Multiplication-Sign 3 Gy were compared with 162 patients receiving 5 Multiplication-Sign 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS {>=} 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS {>=} 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.

  7. Type A Investigation of the Electrical Arc Injury at the Stanford Linear

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Accelerator Complex on October 11, 2004 | Department of Energy of the Electrical Arc Injury at the Stanford Linear Accelerator Complex on October 11, 2004 Type A Investigation of the Electrical Arc Injury at the Stanford Linear Accelerator Complex on October 11, 2004 November 15, 2004 On October 11, 2004, at approximately 11:15 am, a subcontractor electrician working at the Stanford Linear Accelerator Center (SLAC) received serious burn injuries requiring hospitalization due to an electrical

  8. Investigation of the July 1, 2011, Fall Injury at the Savannah River Site |

    Office of Environmental Management (EM)

    Department of Energy July 1, 2011, Fall Injury at the Savannah River Site Investigation of the July 1, 2011, Fall Injury at the Savannah River Site August 8, 2011 On July 1, 2011, a worker fell from portable scaffolding during facility modifications in the Purification Area Vault (PAV) of Building 105-K at the Savannah River Site (SRS). The worker required hospitalization due to sustained head injury and numerous broken ribs. This accident meets Accident Investigation Criteria 2.a.2 of

  9. 2010 East Tennessee Technology Park Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-08-16

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  10. 2010 Y-12 National Security Complex Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-08-31

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  11. 2010 Oak Ridge National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-07-28

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  12. 2010 Nevada National Security Site Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-07-28

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  13. 2010 Lawrence Livermore National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2011-08-16

    The U.S. Department of Energy's (DOE) commitment to assuring the health and safety of its workers includes the conduct of illness and injury surveillance activities that provide an early warning system to detect health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence, occupational injuries and illnesses, and disabilities and deaths among current workers.

  14. Recovery Act Workers at Y-12 Reach Two Years of Work with No Injuries

    Broader source: Energy.gov [DOE]

    Workers at Oak Ridge’s Y-12 National Security Complex recently celebrated achieving two years of Recovery Act work without a lost workday injury.

  15. COLLOQUIUM: Consciousness and the Social Brain | Princeton Plasma Physics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab September 25, 2013, 4:00pm to 5:30pm Colloquia MBG Auditorium COLLOQUIUM: Consciousness and the Social Brain Professor Michael Graziano Princeton University Presentation: Office presentation icon Presentation What is consciousness and how can a brain, a mere collection of neurons, create it? In my lab we are developing a theoretical and experimental approach to these questions. The theory begins with our ability to attribute awareness to others. The human brain has a complex circuitry

  16. ADR Lunchtime Program: YOUR BRAIN ON CONFLICT | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    YOUR BRAIN ON CONFLICT ADR Lunchtime Program: YOUR BRAIN ON CONFLICT In this workshop we will discuss basic brain structures and functions - how they affect behavior and are affected by behavior. We will also discuss neurotransmitters that are important in both producing and interpreting behavior. This knowledge will form the basis for a discussion of how we can influence behavior during times of conflict. We will take typical situations faced by managers and employees, and apply the knowledge

  17. Final Report on LDRD project 130784 : functional brain imaging...

    Office of Scientific and Technical Information (OSTI)

    cognitive behavior. However, current EROS systems are hampered by poor signal-to-noise-ratio (SNR) and depth of measure, limiting areas of the brain and associated cognitive...

  18. Complex Networks - A Key to Understanding Brain Function

    ScienceCinema (OSTI)

    Olaf Sporns

    2010-01-08

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  19. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect (OSTI)

    Olaf Sporns

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  20. Air-pollution injury on Pinus strobus in Indiana Dunes National Lakeshore - 1985 survey results. Final report

    SciTech Connect (OSTI)

    Sanchini, P.J.

    1986-10-01

    Visible symptoms of ozone injury were observed on 100% of the Eastern white pine trees (Pinus strobus) sampled in 1985 from permanent pine plots at Indiana Dunes National Lakeshore. Average injury was low and affected about 5% of the needle surface. Only 6% of the trees sampled had more than 10% injury. Fleck injury was the most common ozone symptom encountered, followed by tipburn and chlorotic mottle. Significant variation among plots existed in total ozone injury, chlorotic mottle, tipburn, and needle length. Symptoms of other injury types were observed on 9% of the needle surfaces of sampled trees.

  1. Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

    SciTech Connect (OSTI)

    Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

    2013-04-01

    Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients.

  2. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    SciTech Connect (OSTI)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromso, Tromso ; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  3. Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

    SciTech Connect (OSTI)

    Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei

    2011-11-15

    Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

  4. Most Workers Who Suffer Head Injuries- Were Not Wearing Head Protection

    Broader source: Energy.gov [DOE]

    A survey by the U.S. Department of Labor’s Bureau of Labor Statistics (BLS) of accidents and injuries noted that most workers who suffered impact injuries to the head were not wearing head protection. In addition, the same survey showed that the majority of workers were injured while performing their normal jobs at their regular worksites.

  5. Off-the-Job Injuries are on the Rise- and Costly

    Broader source: Energy.gov [DOE]

    Do you have an off-the-job safety program? Should you? The findings from a National Safety Council survey suggest that off-the-job injuries cost companies and society in general as much, if not more than on-the-job injuries!

  6. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    SciTech Connect (OSTI)

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 ?g), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ? Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ? This NM model is a cost effective system to evaluate and optimize therapeutics. ? Show that doxycycline and dexamethasone reduce NM-caused ocular injuries ? Demonstrate that silibinin effectively reverses NM-caused ocular injury endpoints ? Suggest optimization of identified agents against ocular injuries by vesicants.

  7. "USING LASERS TO CONTROL AND PROBE THE BRAIN", Prof. Adam Cohen...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    "USING LASERS TO CONTROL AND PROBE THE BRAIN", Prof. Adam Cohen, Department of Physics, Harvard University USING LASERS TO CONTROL AND PROBE THE BRAIN PPPL Entrance Procedures ...

  8. Type B Accident Investigation Board Report on the Head Injury to a Miner at

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    the Waste Isolation Pilot Plant, Carlsbad, New Mexico - August 25, 2004 | Department of Energy on the Head Injury to a Miner at the Waste Isolation Pilot Plant, Carlsbad, New Mexico - August 25, 2004 Type B Accident Investigation Board Report on the Head Injury to a Miner at the Waste Isolation Pilot Plant, Carlsbad, New Mexico - August 25, 2004 October 15, 2004 On August 25, 2004, an employee of Washington TRU Solution, LLC (WTS) sustained a head injury when he was struck by a C-clamp and

  9. CFTB 04/22/2010 Revisions to the 2008 Census of Fatal Occupational Injuries (CFOI) counts

    National Nuclear Security Administration (NNSA)

    Revisions to the 2008 Census of Fatal Occupational Injuries (CFOI) counts The final count of fatal work injuries in the U.S. in 2008 was 5,214, up from the preliminary count of 5,071 reported in August 2009. The final 2008 total was the lowest annual total since the fatality census was first conducted in 1992. As a result of the updates, the overall 2008 fatal work injury rate for the U.S. rose slightly from 3.6 per 100,000 full-time equivalent workers to 3.7 per 100,000. The final numbers

  10. Compact and mobile high resolution PET brain imager

    DOE Patents [OSTI]

    Majewski, Stanislaw; Proffitt, James

    2011-02-08

    A brain imager includes a compact ring-like static PET imager mounted in a helmet-like structure. When attached to a patient's head, the helmet-like brain imager maintains the relative head-to-imager geometry fixed through the whole imaging procedure. The brain imaging helmet contains radiation sensors and minimal front-end electronics. A flexible mechanical suspension/harness system supports the weight of the helmet thereby allowing for patient to have limited movements of the head during imaging scans. The compact ring-like PET imager enables very high resolution imaging of neurological brain functions, cancer, and effects of trauma using a rather simple mobile scanner with limited space needs for use and storage.

  11. Moab Project Logs 2 Million Work Hours Without Lost-Time Injury...

    Broader source: Energy.gov (indexed) [DOE]

    Remedial Action Project, it represents the number of days without a work-related, lost-time injury or illness, as defined by the Occupational Safety and Health Administration....

  12. DOE-Flex Bulletin-Worker Injury While on a DOE-Flex Arrangement...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Bulletin-Worker Injury While on a DOE-Flex Arrangement Responsible Contacts Bruce Murray HR Policy Advisor E-mail bruce.murray@hq.doe.gov Phone 202-586-3372 More Documents &...

  13. Workers at Paducah Site Exceed 1.5 Million Hours Without Lost-Time Injury, Illness

    Broader source: Energy.gov [DOE]

    PADUCAH, Ky. – Workers with Paducah site infrastructure contractor Swift & Staley, Inc. recently exceeded 1.5 million hours without lost time away from work due to injury or illness, representing nine years of safe performance.

  14. U.S. Recordable Injury and Illness Rates and Lost Workday Rates...

    Office of Environmental Management (EM)

    from 2002 to 2003; both of which are at the lowest level since the Bureau of Labor Statistics (BLS) began reporting this information in the 1970s. PDF icon U.S. Recordable Injury...

  15. Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

    SciTech Connect (OSTI)

    Yu, Victoria; Kishan, Amar U.; Cao, Minsong; Low, Daniel; Lee, Percy; Ruan, Dan

    2014-03-15

    Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Based on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.

  16. 2007 Oak Ridge National Laboratory Annual Illness and Injury Surveillance Report

    SciTech Connect (OSTI)

    U.S. Department of Energy, Office of Health, Safety and Health, Office of Health and Safety, Office of Illness and Injury Prevention Programs

    2009-03-04

    The U.S. Department of Energys (DOE) commitment to assuring the health and safety of its workers includes the conduct of epidemiologic surveillance activities that provide an early warning system for health problems among workers. The Illness and Injury Surveillance Program monitors illnesses and health conditions that result in an absence of workdays, occupational injuries and illnesses, and disabilities and deaths among current workers.

  17. Type B Accident Investigation of the August 22, 2000, Injury Resulting From

    Office of Environmental Management (EM)

    Violent Exothermic Chemical Reaction at the Portsmouth Gaseous Diffusion Plant, X-701B Site | Department of Energy August 22, 2000, Injury Resulting From Violent Exothermic Chemical Reaction at the Portsmouth Gaseous Diffusion Plant, X-701B Site Type B Accident Investigation of the August 22, 2000, Injury Resulting From Violent Exothermic Chemical Reaction at the Portsmouth Gaseous Diffusion Plant, X-701B Site October 20, 2000 On August 22, 2000, an accident occurred at the U. S. Department

  18. Type B Accident Investigation Report of the October 28, 2004, Burn Injuries

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Sustained During an Office of Secure Transportation Joint Training Exercise at Fort Hunter-Liggett, CA | Department of Energy of the October 28, 2004, Burn Injuries Sustained During an Office of Secure Transportation Joint Training Exercise at Fort Hunter-Liggett, CA Type B Accident Investigation Report of the October 28, 2004, Burn Injuries Sustained During an Office of Secure Transportation Joint Training Exercise at Fort Hunter-Liggett, CA February 1, 2005 TYPE B Accident Investigation

  19. Type B Accident Investigation on the February 17, 2004, Personal Injury

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Accident, Bettis Atomic Power Laboratory | Department of Energy on the February 17, 2004, Personal Injury Accident, Bettis Atomic Power Laboratory Type B Accident Investigation on the February 17, 2004, Personal Injury Accident, Bettis Atomic Power Laboratory August 16, 2004 Prime contractors need to provide a safe work environment for the entire facility site, including parking lots and outdoor pedestrian walkways. Particular attention needs to be given to areas that must be traversed by

  20. 'Safety Begins with Me' Works toward an Injury-Free Workplace at

    Energy Savers [EERE]

    Savannah River Site - Employees embrace high-quality safety awareness campaign | Department of Energy 'Safety Begins with Me' Works toward an Injury-Free Workplace at Savannah River Site - Employees embrace high-quality safety awareness campaign 'Safety Begins with Me' Works toward an Injury-Free Workplace at Savannah River Site - Employees embrace high-quality safety awareness campaign February 1, 2012 - 12:00pm Addthis A Savannah River Nuclear Solutions employee hangs one of several

  1. Chronic, Multi-Contact, Neural Interface for Deep Brain Stimulation

    Office of Scientific and Technical Information (OSTI)

    (Conference) | SciTech Connect Chronic, Multi-Contact, Neural Interface for Deep Brain Stimulation Citation Details In-Document Search Title: Chronic, Multi-Contact, Neural Interface for Deep Brain Stimulation Authors: Tooker, A C ; Madsen, T E ; Crowell, A ; Shah, K G ; Felix, S H ; Mayberg, H S ; Pannu, S S ; Rainnie, D G ; Tolosa, V M Publication Date: 2013-09-30 OSTI Identifier: 1108838 Report Number(s): LLNL-CONF-644462 DOE Contract Number: W-7405-ENG-48 Resource Type: Conference

  2. Unlocking the Secrets of Brain Signals (4K)

    SciTech Connect (OSTI)

    2015-08-17

    Scientists have for the first time determined, at atomic-scale resolution, the 3-D structure of a protein complex that provides the ultrafast trigger for chemicals messages sent between nerve cells in our brains. The discovery, which provides a new understanding of the molecular machinery driving brain function, builds on decades of research at Stanford University, the Stanford School of Medicine and SLAC National Accelerator Laboratory was made possible by SLAC’s Linac Coherent Light Source, an ultrabright X-ray laser.

  3. Preliminary Results of Whole Brain Radiotherapy With Concurrent Trastuzumab for Treatment of Brain Metastases in Breast Cancer Patients

    SciTech Connect (OSTI)

    Chargari, Cyrus; Idrissi, Hind Riahi; Pierga, Jean-Yves; Bollet, Marc A.; Dieras, Veronique; Campana, Francois; Cottu, Paul; Fourquet, Alain; Kirova, Youlia M.

    2011-11-01

    Purpose: To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer. Methods and Materials: Between April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRT delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience. Results: After WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed. Conclusion: The low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial.

  4. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    SciTech Connect (OSTI)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ? Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ? Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ? Post-exposure rolipram treatments by both systemic and local delivery were effective. ? Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

  5. What Art Can Tell Us About The Brain | Princeton Plasma Physics...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    MBG Auditorium What Art Can Tell Us About The Brain Dr. Margaret Livingstone, Professor of ... Science On Saturday, March 15, 2014, "What Art Can Tell Us About The Brain" Contact ...

  6. Brain surgery breathes new life into aging plants

    SciTech Connect (OSTI)

    Makansi, J.

    2006-04-15

    Unlike managing the human aging process, extending the life of a power plant often includes brain surgery, modernizing its control and automation system. Lately, such retrofits range from wholesale replacing of existing controls to the addition of specific control elements that help optimize performance. Pending revisions to safety codes and cybersecurity issues also need to be considered. 4 figs.

  7. Type B Accident Investigation Board Report BNFL, Inc. Employee Foot Injury

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    on December 17, 2003, at the East Tennessee Technology Park Building K-31 | Department of Energy BNFL, Inc. Employee Foot Injury on December 17, 2003, at the East Tennessee Technology Park Building K-31 Type B Accident Investigation Board Report BNFL, Inc. Employee Foot Injury on December 17, 2003, at the East Tennessee Technology Park Building K-31 February 1, 2004 On December 17, 2003, at approximately 7:15 a.m., an accident occurred at the U.S. Department of Energy (DOE) East Tennessee

  8. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    SciTech Connect (OSTI)

    Choi, Hong-Seok; Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min; Park, Jeong-Ho; Kim, Jae-Il; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

    2014-05-30

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the neuropathological changes associated with prion disease.

  9. Investigation of injury/illness data at a nuclear facility. Part II

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Cournoyer, Michael E.; Garcia, Vincent E.; Sandoval, Arnold N.; George, Gerald L.; Gubernatis, David C.; Schreiber, Stephen B.

    2015-07-01

    At Los Alamos National Laboratory (LANL), there are several nuclear facilities, accelerator facilities, radiological facilities, explosives sites, moderate- and high-hazard non-nuclear facilities, biosciences laboratory, etc. The Plutonium Science and Manufacturing Directorate (ADPSM) provides special nuclear material research, process development, technology demonstration, and manufacturing capabilities. ADPSM manages the LANL Plutonium Facility. Within the Radiological Control Area at TA-55 (PF-4), chemical and metallurgical operations with plutonium and other hazardous materials are performed. LANL Health and Safety Programs investigate injury and illness data. In this study, statistically significant trends have been identified and compared for LANL, ADPSM, and PF-4 injury/illness cases. A previouslymore » described output metric is used to measures LANL management progress towards meeting its operational safety objectives and goals. Timelines are used to determine trends in Injury/Illness types. Pareto Charts are used to prioritize causal factors. The data generated from analysis of Injury/Illness data have helped identify and reduce the number of corresponding causal factors.« less

  10. Quantifying mortal injury of juvenile Chinook salmon exposed to simulated hydro-turbine passage

    SciTech Connect (OSTI)

    Brown, Richard S.; Carlson, Thomas J.; Gingerich, Andrew J.; Stephenson, John R.; Pflugrath, Brett D.; Welch, Abigail E.; Langeslay, Mike; Ahmann, Martin L.; Johnson, Robert L.; Skalski, John R.; Seaburg, Adam; Townsend, Richard L.

    2012-02-01

    A proportion of juvenile Chinook salmon and other salmonids travel through one or more turbines during seaward migration in the Columbia and Snake River every year. Despite this understanding, limited information exists on how these fish respond to hydraulic pressures found during turbine passage events. In this study we exposed juvenile Chinook salmon to varied acclimation pressures and subsequent exposure pressures (nadir) to mimic the hydraulic pressures of large Kaplan turbines (ratio of pressure change). Additionally, we varied abiotic (total dissolved gas, rate of pressure change) and biotic (condition factor, fish length, fish weight) factors that may contribute to the incidence of mortal injury associated with fish passing through hydro-turbines. We determined that the main factor associated with mortal injury of juvenile Chinook salmon during simulated turbine passage was the ratio between acclimation and nadir pressures. Condition factor, total dissolved gas, and the rate of pressure change were found to only slightly increase the predictive power of equations relating probability of mortal injury to conditions of exposure or characteristics of test fish during simulated turbine passage. This research will assist engineers and fisheries managers in operating and improving hydroelectric facility efficiency while minimizing mortality and injury of turbine-passed juvenile Chinook salmon. The results are discussed in the context of turbine development and the necessity of understanding how different species of fish will respond to the hydraulic pressures of turbine passage.

  11. Investigation of injury/illness data at a nuclear facility. Part II

    SciTech Connect (OSTI)

    Cournoyer, Michael E.; Garcia, Vincent E.; Sandoval, Arnold N.; George, Gerald L.; Gubernatis, David C.; Schreiber, Stephen B.

    2015-07-01

    At Los Alamos National Laboratory (LANL), there are several nuclear facilities, accelerator facilities, radiological facilities, explosives sites, moderate- and high-hazard non-nuclear facilities, biosciences laboratory, etc. The Plutonium Science and Manufacturing Directorate (ADPSM) provides special nuclear material research, process development, technology demonstration, and manufacturing capabilities. ADPSM manages the LANL Plutonium Facility. Within the Radiological Control Area at TA-55 (PF-4), chemical and metallurgical operations with plutonium and other hazardous materials are performed. LANL Health and Safety Programs investigate injury and illness data. In this study, statistically significant trends have been identified and compared for LANL, ADPSM, and PF-4 injury/illness cases. A previously described output metric is used to measures LANL management progress towards meeting its operational safety objectives and goals. Timelines are used to determine trends in Injury/Illness types. Pareto Charts are used to prioritize causal factors. The data generated from analysis of Injury/Illness data have helped identify and reduce the number of corresponding causal factors.

  12. Moab Project Exceeds 5 Years of Operations Without Lost-Time Injury, Illness

    Broader source: Energy.gov [DOE]

    GRAND JUNCTION, Colo. – It has been more than five years since workers on the Moab Uranium Mill Tailings Remedial Action Project in Utah had a lost-time injury or illness. This represents roughly 2.2 million hours of safe work.

  13. Moab Project Logs 2 Million Work Hours Without Lost-Time Injury or Illness

    Broader source: Energy.gov [DOE]

    GRAND JUNCTION, Colo. – The number 1,584 may not mean much to most people, but for the workers on EM’s Moab Uranium Mill Tailings Remedial Action Project, it represents the number of days without a work-related, lost-time injury or illness, as defined by the Occupational Safety and Health Administration.

  14. Operating Experience Level 3, Ergonomically Correct Equipment Can Decrease the Risk for Work Station Injuries

    Broader source: Energy.gov [DOE]

    OE-3 2016-02: This Operating Experience Level 3 (OE-3) document provides information that managers and workers at Department of Energy (DOE) facilities can use to improve productivity and comfort, while also decreasing the risk for musculoskeletal disorders (MSDs) and injuries when working at or around a computer work station for extended periods.

  15. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    SciTech Connect (OSTI)

    Crdenas-Gonzlez, Mariana C.; Del Razo, Luz M.; Barrera-Chimal, Jonatan; Jacobo-Estrada, Tania; Lpez-Bayghen, Esther; and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary ?-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: Exposure to low concentrations of fluoride induced proximal tubular injury Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels. Fluoride increased kidney injury biomarkers at stages where eGFR was unaltered.

  16. Source localization of brain activity using helium-free interferometer

    SciTech Connect (OSTI)

    Dammers, Jürgen Chocholacs, Harald; Eich, Eberhard; Boers, Frank; Faley, Michael; Dunin-Borkowski, Rafal E.; Jon Shah, N.

    2014-05-26

    To detect extremely small magnetic fields generated by the human brain, currently all commercial magnetoencephalography (MEG) systems are equipped with low-temperature (low-T{sub c}) superconducting quantum interference device (SQUID) sensors that use liquid helium for cooling. The limited and increasingly expensive supply of helium, which has seen dramatic price increases recently, has become a real problem for such systems and the situation shows no signs of abating. MEG research in the long run is now endangered. In this study, we report a MEG source localization utilizing a single, highly sensitive SQUID cooled with liquid nitrogen only. Our findings confirm that localization of neuromagnetic activity is indeed possible using high-T{sub c} SQUIDs. We believe that our findings secure the future of this exquisitely sensitive technique and have major implications for brain research and the developments of cost-effective multi-channel, high-T{sub c} SQUID-based MEG systems.

  17. NREL Adds Eyes, Brains to Occupancy Detection - News Feature | NREL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NREL Adds Eyes, Brains to Occupancy Detection June 4, 2013 This photo shows the inside of the IPOS device, with three black plugs connected to a green circuit board that holds a variety of electronics. Enlarge image Inside view of the computer in the Image Processing Occupancy Sensor (IPOS). The IPOS uses a synergistic approach with human face and motion detection through computer vision algorithms. The IPOS classifies additional information including the number of occupants, their positions on

  18. Developments in deep brain stimulation using time dependent magnetic fields

    SciTech Connect (OSTI)

    Crowther, L.J.; Nlebedim, I.C.; Jiles, D.C.

    2012-03-07

    The effect of head model complexity upon the strength of field in different brain regions for transcranial magnetic stimulation (TMS) has been investigated. Experimental measurements were used to verify the validity of magnetic field calculations and induced electric field calculations for three 3D human head models of varying complexity. Results show the inability for simplified head models to accurately determine the site of high fields that lead to neuronal stimulation and highlight the necessity for realistic head modeling for TMS applications.

  19. Treatment of Five or More Brain Metastases With Stereotactic Radiosurgery

    SciTech Connect (OSTI)

    Hunter, Grant K.; Suh, John H.; Reuther, Alwyn M.; Vogelbaum, Michael A.; Barnett, Gene H.; Angelov, Lilyana; Weil, Robert J.; Neyman, Gennady; Chao, Samuel T.

    2012-08-01

    Purpose: To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). Methods and Materials: Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). Results: The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of {>=}80 significantly influenced OS (median OS, 4.8 months for KPS {<=}70 vs. 8.8 months for KPS {>=}80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of {<=}70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). Conclusions: Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of {>=}80 predicts for an improved outcome.

  20. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    SciTech Connect (OSTI)

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-03-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or distant recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.

  1. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    SciTech Connect (OSTI)

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-06-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.

  2. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    SciTech Connect (OSTI)

    Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1?, IL-6, and TNF-?), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: Iron supplementation at high altitudes induced lung histological changes in rats. Iron induced oxidative stress in lung tissues of rats at high altitudes. Iron increased the levels of IL-1?, IL-6 and TNF-? in lung tissues at high altitudes. Trolox alleviated the iron-induced histological and biochemical changes to the lungs.

  3. Audit of Department of Energy Contractor Occupational Injury and Illness Reporting Practices, IG-0404

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    May 7, 1997 MEMORANDUM FOR THE SECRETARY FROM: John C. Layton Inspector General SUBJECT: INFORMATION: Report on "Audit of Department of Energy Contractor Occupational Injury and Illness Reporting Practices" BACKGROUND: The Department and its contractors are responsible for ensuring that a safe and healthy work environment is provided to Department and contractor employees at its operating facilities. Contractors are responsible for establishing a comprehensive occupational safety and

  4. Special Illness and Injury Surveillance Reports Worker Health Summary, 1995-2004

    Energy Savers [EERE]

    Available upon request (.PDF) Special Illness and Injury Surveillance Reports Worker Health Summary, 1995-2004 Worker Health at a Glance, 2000-2009 Worker Health at a Glance, 1995-2004 Brookhaven Cancer Assessment Distribution of Cancer Among Former and Current Brookhaven National Laboratory Workers PETC Mortality Study Pittsburgh Energy Technology Center Worker Mortality Update Annual Reports (Alphabetic by Site) Argonne National Laboratory 2010 Annual Report for Argonne National Laboratory

  5. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2?) (LCMS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: Male mice were more susceptible to hyperoxic lung injury than females. Sex differences in inflammatory markers were observed. CYP1A expression was higher in females after hyperoxia exposure.

  6. Mitofusin-2 protects against cold stress-induced cell injury in HEK293 cells

    SciTech Connect (OSTI)

    Zhang, Wenbin; Chen, Yaomin; Yang, Qun; Che, Honglei; Chen, Xiangjun; Yao, Ting; Zhao, Fang; Liu, Mingchao; Ke, Tao; Chen, Jingyuan; Luo, Wenjing

    2010-06-25

    Mitochondrial impairment is hypothesized to contribute to cell injury during cold stress. Mitochondria fission and fusion are closely related in the function of the mitochondria, but the precise mechanisms whereby these processes regulate cell injury during cold stress remain to be determined. HEK293 cells were cultured in a cold environment (4.0 {+-} 0.1 {sup o}C) for 2, 4, 8, or 12 h. Western blot analyses showed that these cells expressed decreased fission-related protein Drp1 and increased fusion-related protein Mfn2 at 4 h; meanwhile, electron microscopy analysis revealed large and long mitochondrial morphology within these cells, indicating increased mitochondrial fusion. With silencing of Mfn2 but not of Mfn1 by siRNA promoted cold-stress-induced cell death with decreased ATP production in HEK293 cells. Our results show that increased expression of Mfn2 and mitochondrial fusion are important for mitochondrial function as well as cell survival during cold stress. These findings have important implications for understanding the mechanisms of mitochondrial fusion and fission in cold-stress-induced cell injury.

  7. Final Report on LDRD project 130784 : functional brain imaging by tunable

    Office of Scientific and Technical Information (OSTI)

    multi-spectral Event-Related Optical Signal (EROS). (Technical Report) | SciTech Connect Final Report on LDRD project 130784 : functional brain imaging by tunable multi-spectral Event-Related Optical Signal (EROS). Citation Details In-Document Search Title: Final Report on LDRD project 130784 : functional brain imaging by tunable multi-spectral Event-Related Optical Signal (EROS). Functional brain imaging is of great interest for understanding correlations between specific cognitive

  8. High School Students Gear Up for Battle of the Brains

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    High School Students Gear Up for Battle of the Brains For more information contact: Sarah Holmes Barba, 303-275-3023 email: Sarah Holmes Barba Golden, Colo., Feb. 13, 2001 - How many prime numbers are there between 30 and 60? Starch is the polymer of what monosaccharide? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 24 at the Colorado School of Mines in Golden. Thirty-two

  9. High performance nanobio photocatalyst for targeted brain cancer therapy.

    SciTech Connect (OSTI)

    Rozhkova, E.; Ulasov, I.; Dimitrijevic, N. M.; Lesniak, M.; Rajh, T.; Lai, B.; Center for Nanoscale Materials

    2009-09-01

    We report pronounced and specific antiglioblastoma cell phototoxicity of 5 nm TiO{sub 2} particles covalently tethered to an antibody via a dihydroxybenzene bivalent linker. The linker application enables absorption of a visible part of the solar spectrum by the nanobio hybrid. The phototoxicity is mediated by reactive oxygen species (ROS) that initiate programmed death of the cancer cell. Synchrotron X-ray fluorescence microscopy (XFM) was applied for direct visualization of the nanobioconjugate distribution through a single brain cancer cell at the submicrometer scale.

  10. Conformable actively multiplexed high-density surface electrode array for brain interfacing

    DOE Patents [OSTI]

    Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

    2015-01-13

    Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

  11. Method and apparatus for extraction of low-frequency artifacts from brain waves for alertness detection

    DOE Patents [OSTI]

    Clapp, N.E.; Hively, L.M.

    1997-05-06

    Methods and apparatus automatically detect alertness in humans by monitoring and analyzing brain wave signals. Steps include: acquiring the brain wave (EEG or MEG) data from the subject, digitizing the data, separating artifact data from raw data, and comparing trends in f-data to alertness indicators, providing notification of inadequate alertness. 4 figs.

  12. Method and apparatus for extraction of low-frequency artifacts from brain waves for alertness detection

    DOE Patents [OSTI]

    Clapp, Ned E.; Hively, Lee M.

    1997-01-01

    Methods and apparatus automatically detect alertness in humans by monitoring and analyzing brain wave signals. Steps include: acquiring the brain wave (EEG or MEG) data from the subject, digitizing the data, separating artifact data from raw data, and comparing trends in f-data to alertness indicators, providing notification of inadequate alertness.

  13. Multipinhole collimator with 20 apertures for a brain SPECT application

    SciTech Connect (OSTI)

    Lee, Tzu-Cheng; Ellin, Justin R.; Shrestha, Uttam; Seo, Youngho; Huang, Qiu; Gullberg, Grant T.

    2014-11-01

    Purpose: Several new technologies for single photon emission computed tomography (SPECT) instrumentation with parallel-hole collimation have been proposed to improve detector sensitivity and signal collection efficiency. Benefits from improved signal efficiency include shorter acquisition times and lower dose requirements. In this paper, the authors show a possibility of over an order of magnitude enhancement in photon detection efficiency (from 7.6 × 10{sup −5} to 1.6 × 10{sup −3}) for dopamine transporter (DaT) imaging of the striatum over the conventional SPECT parallel-hole collimators by use of custom-designed 20 multipinhole (20-MPH) collimators with apertures of 0.75 cm diameter. Methods: Quantifying specific binding ratio (SBR) of {sup 123}I-ioflupane or {sup 123}I-iometopane’s signal at the striatal region is a common brain imaging method to confirm the diagnosis of the Parkinson’s disease. The authors performed imaging of a striatal phantom filled with aqueous solution of I-123 and compared camera recovery ratios of SBR acquired between low-energy high-resolution (LEHR) parallel-hole collimators and 20-MPH collimators. Results: With only two-thirds of total acquisition time (20 min against 30 min), a comparable camera recovery ratio of SBR was achieved using 20-MPH collimators in comparison to that from the LEHR collimator study. Conclusions: Their systematic analyses showed that the 20-MPH collimator could be a promising alternative for the DaT SPECT imaging for brain over the traditional LEHR collimator, which could give both shorter scan time and improved diagnostic accuracy.

  14. Cell density signal protein suitable for treatment of connective tissue injuries and defects

    DOE Patents [OSTI]

    Schwarz, Richard I.

    2002-08-13

    Identification, isolation and partial sequencing of a cell density protein produced by fibroblastic cells. The cell density signal protein comprising a 14 amino acid peptide or a fragment, variant, mutant or analog thereof, the deduced cDNA sequence from the 14 amino acid peptide, a recombinant protein, protein and peptide-specific antibodies, and the use of the peptide and peptide-specific antibodies as therapeutic agents for regulation of cell differentiation and proliferation. A method for treatment and repair of connective tissue and tendon injuries, collagen deficiency, and connective tissue defects.

  15. ORISE-09-OEWH-0176 POISSON REGRESSION ANALYSIS OF ILLNESS AND INJURY SURVEILLANCE DATA

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ORISE-09-OEWH-0176 POISSON REGRESSION ANALYSIS OF ILLNESS AND INJURY SURVEILLANCE DATA E. L. Frome J. P. Watkins E. D. Ellis Center for Epidemiologic Research Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA C. H. Strader U. S. Department of Energy Date Published: December 2012 Prepared by Oak Ridge Institute for Science and Education P.O. Box 117 Oak Ridge, TN 37831-0117 managed by Oak Ridge Associated Universities for the U.S. DEPARTMENT OF ENERGY under contract

  16. From: Meredith Brown <racer@lanl.gov> Subject: Yellow Alert: Fall Results in Injury

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Tue, 16 Jun 1998 13:57:16 -0500 From: Meredith Brown <racer@lanl.gov> Subject: Yellow Alert: Fall Results in Injury Title: Fall From Ladder Results in Fractured Vertebra Identifier: LLNL-1998-002 Date: January 5, 1998 Lesson Learned Statement: Work at elevated levels needs to be thoroughly evaluated. Discussion of Activities: A subcontractor employee was soldering a pipe while standing 2/3 of the way up a portable ten foot ladder when he lost his balance and fell six feet to the floor

  17. Foot Drop after Ethanol Embolization of Calf Vascular Malformation: A Lesson on Nerve Injury

    SciTech Connect (OSTI)

    Tay, Vincent Khwee-Soon; Mohan, P. Chandra; Liew, Wendy Kein Meng; Mahadev, Arjandas; Tay, Kiang Hiong

    2013-08-01

    Ethanol is often used in sclerotherapy to treat vascular malformations. Nerve injury is a known complication of this procedure. However, the management of this complication is not well described in literature. This case describes a 10-year-old boy with a slow flow vascular malformation in the right calf who underwent transarterial ethanol embolization following prior unsuccessful direct percutaneous sclerotherapy. The development of a dense foot drop that subsequently recovered is described, and the management of this uncommon but distressful complication is discussed.

  18. DOE-Flex Bulletin-Worker Injury While on a DOE-Flex Arrangement

    Office of Environmental Management (EM)

    Flex Bulletin The information contained in this Bulletin is intended for DOE-Flex Advisors and Coordinators in responding to questions. The information supplements the guidance in the Handbook on DOE- Flex and will be incorporated in the handbook in the near future, at which fime this Builetin wil! expire and be removed from the DOE-Flex web site No. 2 May 2000 Subject: Worker In~jury While on a DOE-Flex Arrangement This Bulletin responds to questions that have surfaced regarding DOE'S liability

  19. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    SciTech Connect (OSTI)

    Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy; Gow, Andrew J.; Sinko, Patrick J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 /day, 1 d3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ? Nitrogen mustard (NM) induces acute lung injury and fibrosis. ? Pulmonary toxicity is associated with increased expression of iNOS. ? Transient inhibition of iNOS attenuates acute lung injury induced by NM.

  20. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    SciTech Connect (OSTI)

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Department of Medical Biophysics, University of Toronto, Toronto ; Wong, C. Shun; Department of Medical Biophysics, University of Toronto, Toronto; Department of Radiation Oncology, University of Toronto, Toronto ; Nieman, Brian J.

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  1. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    SciTech Connect (OSTI)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-10-01

    Although estrogen receptor (ER)? agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemiareperfusion. The functional mechanisms of ER? have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ER? agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ER?-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ER? in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ? Liver injury induced by drugs or chemicals was investigated in mice. ? Liver injury was suppressed by pretreatment with tamoxifen in female mice. ? Mmd2, whose function was unknown, could be a candidate gene for liver protection. ? Tamoxifen up-regulated Mmd2 mRNA expression via ER?.

  2. A hungry brain slurps up a kid's energy | OpenEI Community

    Open Energy Info (EERE)

    4 September, 2014 - 15:40 Human energy can be considered a type of renewable energy. Science News reports on how children's brains use almost half of the energy their bodies...

  3. U.S. Recordable Injury and Illness Rates and Lost Workday Rates Lowest Since BLS Began Reporting

    Broader source: Energy.gov [DOE]

    Acting Assistant Secretary for the Occupational Safety and Health Administration (OSHA), Jonathan L. Snare, told a gathering of safety and health professionals at the American Society of Safety Engineers Annual National Conference in New Orleans, LA, that the nation’s recordable injury and illness rates have declined 7.1 percent from 2002 to 2003.

  4. "USING LASERS TO CONTROL AND PROBE THE BRAIN", Prof. Adam Cohen, Department

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of Physics, Harvard University | Princeton Plasma Physics Lab February 18, 2012, 9:30am Science On Saturday "USING LASERS TO CONTROL AND PROBE THE BRAIN", Prof. Adam Cohen, Department of Physics, Harvard University USING LASERS TO CONTROL AND PROBE THE BRAIN PPPL Entrance Procedures Visitor Information, Directions, Security at PPPL As a federal facility, the Princeton Plasma Physics Laboratory is operating under heightened security measures because of the events of September 11,

  5. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    SciTech Connect (OSTI)

    Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

    2013-11-15

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in patients with brain metastases after RT to the brain, whereas it remained relatively stable in breast cancer patients.

  6. A planning study of simultaneous integrated boost with forward IMRT for multiple brain metastases

    SciTech Connect (OSTI)

    Liang, Xiaodong; Ni, Lingqin; Hu, Wei; Chen, Weijun; Ying, Shenpeng; Gong, Qiangjun; Liu, Yanmei

    2013-07-01

    The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 to 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.

  7. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    SciTech Connect (OSTI)

    Fullerton, Aaron M.; Roth, Robert A.; Ganey, Patricia E.

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 ?g/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (410 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFN?), and TCDD/Con A-induced hepatotoxicity was attenuated in IFN? knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cellcell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFN? and FasL expression. -- Highlights: ? TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ? TCDD pretreatment increased concentration of IFN? in plasma after Con A. ? Con A-induced activation of NKT cells was increased by TCDD pretreatment. ? FasL-positive NKT cells increased with TCDD pretreatment versus Con A alone. ? IFN? and FasL are critical to the development of liver injury from TCDD/Con A.

  8. ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

    SciTech Connect (OSTI)

    Arfian, Nur; Emoto, Noriaki; Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe ; Vignon-Zellweger, Nicolas; Nakayama, Kazuhiko; Yagi, Keiko; Hirata, Ken-ichi

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secreted by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and ET{sub A} receptor expression. This was accompanied by tubular injury, wall thickening and reduction of lumen area/wall area ratio of small renal arteries, increased oxidative stress and inflammation. These parameters were attenuated in VEETKO mice. Conclusion: Our results suggest that suppression of ET-1 from the endothelial cells attenuates IRI kidney injury. Blocking ET-1 effects may represent a therapeutic strategy in the management of AKI.

  9. A Preliminary Assessment of Barotrauma Injuries and Acclimation Studies for Three Fish Species

    SciTech Connect (OSTI)

    Brown, Richard S.; Walker, Ricardo W.; Stephenson, John R.

    2015-12-15

    Fish that pass hydro structures either through turbine passage, deep spill, or other deep pathways can experience rapid decreases in pressure that can result in barotrauma. In addition to morphology and physiology of the fishs swim bladder, the severity of barotrauma is directly related to the volume of undissolved gas in fish prior to rapid decompression and the lowest pressure the fish experience as they pass hydro structures (termed the nadir). The volume of undissolved gas in fish is influenced by the depth of acclimation (the pressure at which the fish is neutrally buoyant); therefore, determining the depth where fish are neutrally buoyant is a critical precursor to determining the relationship between pressure changes and injury or mortality.

  10. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    SciTech Connect (OSTI)

    Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar; Tokar, Erik J.; Kadiiska, Maria B.; Waalkes, Michael P.; Mason, Ronald P.; Chatterjee, Saurabh

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-? levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ? BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ? BDCM-induced higher leptin contributes to early steatohepatitic lesions. ? Increased leptin mediates protein radical and 3-nitrotyrosine formation. ? BDCM exposure in obesity activates Kupffer cells and NADPH oxidase. ? BDCM/leptin synergy promotes necrotic cell-death and augments steatohepatitis.

  11. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    SciTech Connect (OSTI)

    Sahgal, Arjun; Aoyama, Hidefumi; Kocher, Martin; Neupane, Binod; Collette, Sandra; Tago, Masao; Shaw, Prakesh; Beyene, Joseph; Chang, Eric L.

    2015-03-15

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

  12. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    SciTech Connect (OSTI)

    Han, Eun Young; Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose; Moros, Eduardo; Corry, Peter

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  13. A Multi-institutional Study of Factors Influencing the Use of Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect (OSTI)

    Hodgson, David C.; Charpentier, Anne-Marie; Cigsar, Candemir; Atenafu, Eshetu G.; Ng, Angela; Bahl, Guarav; Zadeh, Gelareh; San Miguel, John; Menard, Cynthia; Department of Radiation Oncology, University of Toronto, Toronto, Ontario

    2013-02-01

    Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors.

  14. Response of rat brain protein synthesis to ethanol and sodium barbital

    SciTech Connect (OSTI)

    Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

    1987-01-01

    Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of /sup 14/C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the /sup 14/C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of /sup 14/C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units.

  15. Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucos Metabolism

    SciTech Connect (OSTI)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Vaska, P.; Fowler, J.S.; Telang, F.; Alexoff, D.; Logan, J.; Wong, C.

    2011-03-01

    The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with ({sup 18}F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes ('on' condition) and once with both cell phones deactivated ('off' condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm{sup 3}) and P < .05 (corrected for multiple comparisons) were considered significant. Brain glucose metabolism computed as absolute metabolism ({micro}mol/100 g per minute) and as normalized metabolism (region/whole brain). Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 {micro}mol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67-4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.

  16. G-protein-coupled estrogen receptor 1 is involved in brain development during zebrafish (Danio rerio) embryogenesis

    SciTech Connect (OSTI)

    Shi, Yanan; Liu, Xiaochun; Zhu, Pei; Li, Jianzhen; Sham, Kathy W.Y.; Cheng, Shuk Han; Li, Shuisheng; Zhang, Yong; Cheng, Christopher H.K.; Lin, Haoran; College of Ocean, Hainan University, Haikou 570228, Hainan

    2013-05-24

    Highlights: •The Gper expression was detected in the developing brain of zebrafish. •Gper morpholino knockdown induced apoptosis of brain cells. •Gper morpholino knockdown reduced expression in neuron markers. •Zebrafish Gper may be involved in neuronal development. -- Abstract: G-protein-coupled estrogen receptor 1 (Gper, formerly known as GPR30) is found to be a trophic and protective factor in mediating action of estrogen in adult brain, while its role in developing brain remains to be elucidated. Here we present the expression pattern of Gper and its functions during embryogenesis in zebrafish. Both the mRNA and protein of Gper were detected throughout embryogenesis. Whole mount in situ hybridization (WISH) revealed a wide distribution of gper mRNAs in various regions of the developing brain. Gper knockdown by specific morpholinos resulted in growth retardation in embryos and morphological defects in the developing brain. In addition, induced apoptosis, decreased proliferation of the brain cells and maldevelopment of sensory and motor neurons were also found in the morphants. Our results provide novel insights into Gper functions in the developing brain, revealing that Gper can maintain the survival of the brain cells, and formation and/or differentiation of the sensory and motor neurons.

  17. Comparison of Clinical Outcomes of Surgery Followed by Local Brain Radiotherapy and Surgery Followed by Whole Brain Radiotherapy in Patients With Single Brain Metastasis: Single-Center Retrospective Analysis

    SciTech Connect (OSTI)

    Hashimoto, Kenji; Narita, Yoshitaka; Miyakita, Yasuji; Ohno, Makoto; Sumi, Minako; Mayahara, Hiroshi; Kayama, Takamasa; Shibui, Soichiro

    2011-11-15

    Purpose: Data comparing the clinical outcomes of local brain radiotherapy (LBRT) and whole brain RT (WBRT) in patients with a single brain metastasis after tumor removal are limited. Patients and Methods: A retrospective analysis was performed to compare the patterns of treatment failure, cause of death, progression-free survival, median survival time, and Karnofsky performance status for long-term survivors among patients who underwent surgery followed by either LBRT or WBRT between 1990 and 2008 at the National Cancer Center Hospital. Results: A total of 130 consecutive patients were identified. The median progression-free survival period among the patients who received postoperative LBRT (n = 64) and WBRT (n = 66) was 9.7 and 11.5 months, respectively (p = .75). The local recurrence rates (LBRT, 9.4% vs. WBRT, 12.1%) and intracranial new metastasis rate (LBRT, 42.2% vs. WBRT, 33.3%) were similar in each arm. The incidence of leptomeningeal metastasis was also equivalent (LBRT, 9.4% vs. WBRT, 10.6%). The median survival time for the LBRT and WBRT patients was 13.9 and 16.7 months, respectively (p = .88). A neurologic cause of death was noted in 35.6% of the patients in the LBRT group and 36.7% of the WBRT group (p = .99). The Karnofsky performance status at 2 years was comparable between the two groups. Conclusions: The clinical outcomes of LBRT and WBRT were similar. A prospective evaluation is warranted.

  18. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    SciTech Connect (OSTI)

    Niwinska, Anna; Murawska, Magdalena

    2012-04-01

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of {<=}60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

  19. Intensity-modulated radiosurgery with rapidarc for multiple brain metastases and comparison with static approach

    SciTech Connect (OSTI)

    Wang Jiazhu; Pawlicki, Todd; Rice, Roger; Mundt, Arno J.; Sandhu, Ajay; Lawson, Joshua; Murphy, Kevin T.

    2012-04-01

    Rotational RapidArc (RA) and static intensity-modulated radiosurgery (IMRS) have been used for brain radiosurgery. This study compares the 2 techniques from beam delivery parameters and dosimetry aspects for multiple brain metastases. Twelve patients with 2-12 brain lesions treated with IMRS were replanned using RA. For each patient, an optimal 2-arc RA plan from several trials was chosen for comparison with IMRS. Homogeneity, conformity, and gradient indexes have been calculated. The mean dose to normal brain and maximal dose to other critical organs were evaluated. It was found that monitor unit (MU) reduction by RA is more pronounced for cases with larger number of brain lesions. The MU-ratio of RA and IMRS is reduced from 104% to 39% when lesions increase from 2 to 12. The dose homogeneities are comparable in both techniques and the conformity and gradient indexes and critical organ doses are higher in RA. Treatment time is greatly reduced by RA in intracranial radiosurgery, because RA uses fewer MUs, fewer beams, and fewer couch angles.

  20. Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

    SciTech Connect (OSTI)

    Bender, Edward T.

    2012-11-15

    Purpose: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. Methods: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. Results: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73)Conclusions: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.

  1. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    SciTech Connect (OSTI)

    Kim, Young C. [College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul (Korea, Republic of)], E-mail: youckim@snu.ac.kr; Yim, Hye K.; Jung, Young S. [College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul (Korea, Republic of); Park, Jae H. [College of Veterinary Medicine, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul (Korea, Republic of); Kim, Sung Y. [College of Pharmacy, Wonkwang University, 344-2 Shinyong-Dong, Iksan (Korea, Republic of)

    2007-08-15

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards.

  2. Synchrotron radiation imaging is a powerful tool to image brain microvasculature

    SciTech Connect (OSTI)

    Zhang, Mengqi; Sun, Danni; Xie, Yuanyuan; Xia, Jian; Long, Hongyu; Hu, Kai; Xiao, Bo; Peng, Guanyun

    2014-03-15

    Synchrotron radiation (SR) imaging is a powerful experimental tool for micrometer-scale imaging of microcirculation in vivo. This review discusses recent methodological advances and findings from morphological investigations of cerebral vascular networks during several neurovascular pathologies. In particular, it describes recent developments in SR microangiography for real-time assessment of the brain microvasculature under various pathological conditions in small animal models. It also covers studies that employed SR-based phase-contrast imaging to acquire 3D brain images and provide detailed maps of brain vasculature. In addition, a brief introduction of SR technology and current limitations of SR sources are described in this review. In the near future, SR imaging could transform into a common and informative imaging modality to resolve subtle details of cerebrovascular function.

  3. Enhanced-locality fiber-optic two-photon-fluorescence live-brain interrogation

    SciTech Connect (OSTI)

    Fedotov, I. V.; Doronina-Amitonova, L. V.; Sidorov-Biryukov, D. A.; Fedotov, A. B.; Anokhin, K. V.; Kilin, S. Ya.; Sakoda, K.; Zheltikov, A. M.

    2014-02-24

    Two-photon excitation is shown to substantially enhance the locality of fiber-based optical interrogation of strongly scattering biotissues. In our experiments, a high-numerical-aperture, large-core-are fiber probe is used to deliver the 200-fs output of a 100-MHz mode-locked ytterbium fiber laser to samples of live mouse brain, induce two-photon fluorescence of nitrogen–vacancy centers in diamond markers in brain sample. Fiber probes with a high numerical aperture and a large core area are shown to enable locality enhancement in fiber-laser–fiber-probe two-photon brain excitation and interrogation without sacrificing the efficiency of fluorescence response collection.

  4. The Effect of an Externally Attached Neutrally Buoyant Transmitter on Mortal Injury during Simulated Hydroturbine Passage

    SciTech Connect (OSTI)

    Brown, Richard S.; Pflugrath, Brett D.; Carlson, Thomas J.; Deng, Zhiqun

    2012-02-03

    On their seaward migration, juvenile salmonids commonly pass hydroelectric dams. Fish passing through hydroturbines experience a rapid decrease in pressure as they pass by the turbine blade and the severity of this decompression can be highly variable. This rapid decrease in pressure can result in injuries such as swim bladder rupture, exophthalmia, and emboli and hemorrhaging in the fins and tissues. However, recent research indicates that the presence of a telemetry tag (acoustic, radio, inductive) implanted inside the coelom of a juvenile salmon increases the likelihood that the fish will be injured or die during turbine passage. Thus, previous research conducted using telemetry tags implanted into the coelom of fish may have been inaccurate. Thus, a new technique is needed to provide unbiased estimates of survival through turbines. This research provides an evaluation of the effectiveness of a neutrally buoyant externally attached acoustic transmitter. Both nontagged fish and fish tagged with a neutrally buoyant external transmitter were exposed to a range of rapid decompressions simulating turbine passage. Juvenile Chinook salmon tagged with a neutrally buoyant externally attached acoustic transmitter did not receive a higher degree of barotrauma than their nontagged counterparts. We suggest that future research include field-based comparisons of survival and behavior among fish tagged with a neutrally buoyant external transmitter and those internally implanted with transmitters.

  5. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect (OSTI)

    Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032 ; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin; Institutes of Biomedical Science, Fudan University, Shanghai 200032

    2014-01-03

    Highlights: FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR attenuated alcohol-induced liver injury and steatosis. Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  6. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    SciTech Connect (OSTI)

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  7. SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

    SciTech Connect (OSTI)

    Obeid, L; Adam, J; Tessier, A; Vautrin, M; Benkebil, M; Sihanath, R

    2014-06-01

    Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

  8. Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

    SciTech Connect (OSTI)

    Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

    2007-06-21

    Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

  9. Management of chemical warfare injuries (on CD-ROM). Data file

    SciTech Connect (OSTI)

    1996-08-01

    The threat of use of chemical warfare agents (agents of `mass destruction`) is no longer confined to the battlefield. Agent releases by terrorists in Japan in 1995 served to awaken the world to the dangers faced by civilian communities far removed from centers of armed conflict. The ability to save lives in the event of a chemical agent release turns on provision of immediate and correct medical care in the field and hospital. Being able to ensure availability of life-saving care depends on reaching both military and civilian medical personnel with information on chemical warfare agents and on keeping their skills and knowledge current. While this is of critical importance both to the Department of Defense and to civilian agencies charged with protecting the public, it also is a daunting and potentially expensive task in view of the numbers and geographic dispersion of persons to be trained. The Department of Defense has addressed and overcome these challenges, to the benefit of the military and civilians, by using computer technology as the vehicle by which cost-effective chemical warfare agent training may be conveniently delivered to all who require it. The multi-media instructional program, Management of Chemical Warfare Injuries, was developed for military use by the Naval Health Sciences Education and Training Command, with the technical assistance of the U.S. Army Medical Command. It was originally designed for delivery via video disc, a format used extensively within the Navy. However, in response to a request from the Federal Emergency Management Agency, the Office of the Secretary of Defense agreed to repackage the materials for delivery on CD-ROM in order to make them accessible to a larger audience. In addition, the Navy agreed to include on the two CD-ROMs which contain the program a ready reference not found on the video disc: the Army`s `Medical Management of Chemical Casualties` handbooks for field and medical personnel.

  10. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect (OSTI)

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  11. Salvage Radiosurgery for Brain Metastases: Prognostic Factors to Consider in Patient Selection

    SciTech Connect (OSTI)

    Kurtz, Goldie; Zadeh, Gelareh; Gingras-Hill, Geneviève; Millar, Barbara-Ann; Laperriere, Normand J.; Bernstein, Mark; Jiang, Haiyan; Ménard, Cynthia; Chung, Caroline

    2014-01-01

    Purpose: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. Methods and Materials: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. Results: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. Conclusions: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

  12. Impact of spot size on plan quality of spot scanning proton radiosurgery for peripheral brain lesions

    SciTech Connect (OSTI)

    Wang, Dongxu Dirksen, Blake; Hyer, Daniel E.; Buatti, John M.; Sheybani, Arshin; Dinges, Eric; Felderman, Nicole; TenNapel, Mindi; Bayouth, John E.; Flynn, Ryan T.

    2014-12-15

    Purpose: To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions. Methods: Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP). Results: For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SS plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100–4.49/100) to 6.05/100 (range 1.38/100–11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100–11.5/100) for Cone and 5.22/100 (range 1.37/100–8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322). Conclusions: For treating peripheral brain lesions—where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy—the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.

  13. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    SciTech Connect (OSTI)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas; Shi, Weiji; Riely, Gregory J.; Beal, Kathryn; Yu, Helena A.; Chan, Timothy A.; Zhang, Zhigang; Wu, Abraham J.

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  14. The retention time of inorganic mercury in the brain — A systematic review of the evidence

    SciTech Connect (OSTI)

    Rooney, James P.K.

    2014-02-01

    Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years—contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information. 131 studies of interest were identified. Only 1 primate study made a numeric estimate for the half-life of inorganic mercury (227–540 days). Eighteen human mercury poisoning cases were followed up long term including autopsy. Brain inorganic mercury concentrations at death were consistent with a half-life of several years or longer. 5 radionucleotide studies were found, one of which estimated head half-life (21 days). This estimate has sometimes been misinterpreted to be equivalent to brain half-life—which ignores several confounding factors including limited radioactive half-life and radioactive decay from surrounding tissues including circulating blood. No autopsy cohort study estimated a half-life for inorganic mercury, although some noted bioaccumulation of brain mercury with age. Modelling studies provided some extreme estimates (69 days vs 22 years). Estimates from modelling studies appear sensitive to model assumptions, however predications based on a long half-life (27.4 years) are consistent with autopsy findings. In summary, shorter estimates of half-life are not supported by evidence from animal studies, human case studies, or modelling studies based on appropriate assumptions. Evidence from such studies point to a half-life of inorganic mercury in human brains of several years to several decades. This finding carries important implications for pharmcokinetic modelling of mercury and potentially for the regulatory toxicology of mercury.

  15. Decision Analysis of Stereotactic Radiation Surgery Versus Stereotactic Radiation Surgery and Whole-Brain Radiation Therapy for 1 to 3 Brain Metastases

    SciTech Connect (OSTI)

    Lester-Coll, Nataniel H.; Dosoretz, Arie P.; Yu, James B.

    2014-07-01

    Purpose: Although whole-brain radiation therapy (WBRT) is effective for controlling intracranial disease, it is also associated with neurocognitive side effects. It is unclear whether a theoretically improved quality of life after stereotactic radiation surgery (SRS) alone relative to that after SRS with adjuvant WBRT would justify the omission of WBRT, given the higher risk of intracranial failure. This study compares SRS alone with SRS and WBRT, to evaluate the theoretical benefits of intracranial tumor control with adjuvant WBRT against its possible side effects, using quality-adjusted life expectancy (QALE) as a primary endpoint. Methods and Materials: A Markov decision analysis model was used to compare QALE in a cohort of patients with 1 to 3 brain metastases and Karnofsky performance status of at least 70. Patients were treated with SRS alone or with SRS immediately followed by WBRT. Patients treated with SRS alone underwent surveillance magnetic resonance imaging and received salvage WBRT if they developed intracranial relapse. All patients whose cancer relapsed after WBRT underwent simulation as dying of intracranial progression. Model parameters were estimated from published literature. Results: Treatment with SRS yielded 6.2 quality-adjusted life months (QALMs). The addition of initial WBRT reduced QALE by 1.2 QALMs. On one-way sensitivity analysis, the model was sensitive only to a single parameter, the utility associated with the state of no evidence of disease after SRS alone. At values greater than 0.51, SRS alone was preferred. Conclusions: In general, SRS alone is suggested to have improved quality of life in patients with 1 to 3 brain metastases compared to SRS and immediate WBRT. Our results suggest that immediate treatment with WBRT after SRS can be reserved for patients who would have a poor performance status regardless of treatment. These findings are stable under a wide range of assumptions.

  16. What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

    SciTech Connect (OSTI)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Atalar, Banu; Lieberson, Robert E.; Soltys, Scott G.

    2012-11-01

    Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status ({>=}80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  17. Equal Employment Opportunity: Collaborating for Mission Success

    National Nuclear Security Administration (NNSA)

    ... * October 31, 2011 Lunch-and-Learn on Brain Injuries, sponsored by Douglas Denham. * ... Series "Intuitive Reasoning: A Whole Brain Approach to Problem Solving," sponsored by ...

  18. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    ScienceCinema (OSTI)

    Forte, Trudy

    2011-04-28

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  19. Nicotinic acid increases the lipid content of rat brain synaptosomes. [Ethanol effects

    SciTech Connect (OSTI)

    Basilio, C.; Flores, M.

    1989-02-09

    Chronic administration of nicotinic acid (NA) increase hepatic lipids and potentiates a similar effect induced by ethanol. The amethystic properties of NA promoted us to study its effects on the lipid content of brain synaptosomes of native and ethanol treated rats. Groups of 10 Sprague-Dawley female rats received i.p. either saline, ethanol (4g/kg), NA (50mg/kg), or a mixture of both compounds once a week during 3 weeks. The sleeping time (ST) of the animals receiving ethanol was recorded, brain synaptosomes of all groups were prepared and total lipids (TL) and cholesterol (Chol) content were determined. NA, ethanol and ethanol + NA markedly increased both TL and Chol of synaptosomes. Animals treated with ethanol or ethanol + NA developed tolerance. The group treated with ethanol-NA showed the highest Chol content and slept significantly less than the one treated with ethanol alone indicating that the changes induced by NA favored the appearance of tolerance.

  20. Approaches to the assessment of injuries to soil arising from discharges of hazardous substances and oil: Type B, Technical information document

    SciTech Connect (OSTI)

    Van Voris, P.; Dawson, G.W.; Fredrickson, J.K.; Cataldo, D.A.; Rogers, L.E.; Novich, C.M.; Meuser, J.

    1987-06-01

    Methods for determining the nature and magnitude of injury to the following natural resources are described for: soil chemical characteristics (acidity or pH, cation exchange capacity, percent base saturation, salinity); soil physical characteristics (porosity, water holding capacity, aggregate stability); biological characteristics (microbial activities, invertebrate activities, vegetation); and contaminant transport potential (leaching, food chain). In addition, this document explains how injuries to the soil resource can be translated into a reduction in service provided by that soil and how to determine soil recovery potential. That portion of 43 CFR Part 11 that pertains to the soils portion of the geologic resource is explained.

  1. High School Students Gear Up for Battle of the Brains - News Releases |

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NREL High School Students Gear Up for Battle of the Brains February 6, 2006 Golden, Colo. - The next generation of scientists, mathematicians and engineers will test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 11 at the Colorado School of Mines in Golden. Forty teams from across Colorado will compete in this rapid-fire question-and-answer tournament, which focuses on physics, math, biology, astronomy, chemistry, computers, general science and

  2. "Artificial" brains, electrical grids, and disease modeling: Los Alamos

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    science discoveries unveiled September 15 Science discoveries unveiled "Artificial" brains, electrical grids, and disease modeling: Los Alamos science discoveries unveiled September 15 The event is an opportunity for business leaders and community members to learn about where science is heading, as well as for students to discover potential new career directions. September 8, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez

  3. Top students show off brain power at Kansas City Science Bowl | National

    National Nuclear Security Administration (NNSA)

    Nuclear Security Administration Top students show off brain power at Kansas City Science Bowl | National Nuclear Security Administration Facebook Twitter Youtube Flickr RSS People Mission Managing the Stockpile Preventing Proliferation Powering the Nuclear Navy Emergency Response Recapitalizing Our Infrastructure Countering Nuclear Terrorism About Our Programs Our History Who We Are Our Leadership Our Locations Budget Our Operations Library Bios Congressional Testimony Fact Sheets

  4. High-Tech Brain Implant Predicts, Prevents Epileptic Seizures (ANL-IN-08-043)

    Energy Innovation Portal (Marketing Summaries) [EERE]

    2012-02-07

    Epilepsy, a seizure disorder, affects nearly 3 million people in the United States and 50 million worldwide. Although medication can help treat epilepsy, it has not eliminated seizures for all who live with the condition. Researchers at Argonne National Laboratory—together with researchers from Flint Hills Scientific, LLC, and Biofil, Sarov, Russia—have developed an advanced brain implant system that finds and stops seizures before they happen. This innovation offers...

  5. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    SciTech Connect (OSTI)

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-07-15

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  6. Science & Technology Review March 2010

    SciTech Connect (OSTI)

    Bearinger, J P

    2010-01-29

    This month's issue has the following articles: (1) Countering the Growing Chem-Bio Threat -- Commentary by Penrose (Parney) C. Albright; (2) Responding to a Terrorist Attack Involving Chemical Warfare Agents -- Livermore scientists are helping the nation strengthen plans to swiftly respond to an incident involving chemical warfare agents; (3) Revealing the Secrets of a Deadly Disease -- A Livermore-developed system helps scientists better understand how plague bacteria infect healthy host cells; (4) A New Application for a Weapons Code -- Simulations reveal for the first time how blast waves cause traumatic brain injuries; (5) Testing Valuable National Assets for X-Ray Damage -- Experiments at the National Ignition Facility are measuring the effects of radiation on critical systems; and (6) An Efficient Way to Harness the Sun's Power -- New solar thermal technology is designed to supply residential electric power at nearly half of the current retail price.

  7. Helmet blastometer

    DOE Patents [OSTI]

    Moss, William C; King, Michael J

    2015-03-24

    A helmet blastometer for characterizing the direction, speed, magnitude, and duration of a blast event to determine the likelihood of blast-induced traumatic brain injury (biTBI). Time of arrival (TOA) gage sensors are mounted on a rigid outer shell of the helmet each producing a TOA signal in response to a fast rising blast induced positive pressure change above a predetermined threshold. A receiver analyzes the positive pressure changes from the gages to determine direction, speed, and magnitude of a blast. Other TOA gauge sensors can be used to produce a TOA signal in response to a negative pressure change below a predetermined threshold. The positive and negative pressure change TOA signals are used to determine blast duration. A second set of internal contact pressure sensors is connected to an inner liner of the helmet to detect contact pressure on a user's head to determine if biTBI has been sustained.

  8. Multimodal Imaging of Alzheimer Pathophysiology in the Brain's Default Mode Network

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Shin, Jonghan; Kepe, Vladimir; Small, Gary W.; Phelps, Michael E.; Barrio, Jorge R.

    2011-01-01

    The spatial correlations between the brain's default mode network (DMN) and the brain regions known to develop pathophysiology in Alzheimer's disease (AD) have recently attracted much attention. In this paper, we compare results of different functional and structural imaging modalities, including MRI and PET, and highlight different patterns of anomalies observed within the DMN. Multitracer PET imaging in subjects with and without dementia has demonstrated that [C-11]PIB- and [F-18]FDDNP-binding patterns in patients with AD overlap within nodes of the brain's default network including the prefrontal, lateral parietal, lateral temporal, and posterior cingulate cortices, with the exception of the medial temporalmore » cortex (especially, the hippocampus) where significant discrepancy between increased [F-18]FDDNP binding and negligible [C-11]PIB-binding was observed. [F-18]FDDNP binding in the medial temporal cortex—a key constituent of the DMN—coincides with both the presence of amyloid and tau pathology, and also with cortical areas with maximal atrophy as demonstrated by T1-weighted MR imaging of AD patients.« less

  9. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

    SciTech Connect (OSTI)

    Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jianying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J.; Lapworth, Amanda L.; Llkayeva, Olka; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.; Smith, Richard D.; Qian, Weijun; Lynch, Christopher J.; Newgard, Christopher B.; Buettner, Christoph

    2014-11-04

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity and diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of protein expression and activity of branched-chain alpha keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway in the liver. Selective induction of hypothalamic insulin signaling in rats as well as inducible and lifelong genetic modulation of brain insulin receptor expression in mice both demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Further, short-term overfeeding impairs the ability of brain insulin to lower circulating BCAA levels in rats. Chronic high-fat feeding in primates and obesity and/or type 2 diabetes in humans is associated with reduced BCKDH protein expression in liver, further supporting the concept that decreased hepatic BCKDH is a primary cause of increased plasma BCAA levels in insulin-resistant states. These findings demonstrate that neuroendocrine pathways control BCAA homeostasis and that hypothalamic insulin resistance can be a cause of impaired BCAA metabolism in obesity and diabetes.

  10. Microgravity and Vision in Astronauts | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    brain injuries, which are a major cause of death and permanent injury worldwide. Advances in ultrasound could help lead to better monitoring of changes in pressure in the brain ...

  11. Detecting brain tumor in computed tomography images using Markov random fields and fuzzy C-means clustering techniques

    SciTech Connect (OSTI)

    Abdulbaqi, Hayder Saad; Jafri, Mohd Zubir Mat; Omar, Ahmad Fairuz; Mustafa, Iskandar Shahrim Bin; Abood, Loay Kadom

    2015-04-24

    Brain tumors, are an abnormal growth of tissues in the brain. They may arise in people of any age. They must be detected early, diagnosed accurately, monitored carefully, and treated effectively in order to optimize patient outcomes regarding both survival and quality of life. Manual segmentation of brain tumors from CT scan images is a challenging and time consuming task. Size and location accurate detection of brain tumor plays a vital role in the successful diagnosis and treatment of tumors. Brain tumor detection is considered a challenging mission in medical image processing. The aim of this paper is to introduce a scheme for tumor detection in CT scan images using two different techniques Hidden Markov Random Fields (HMRF) and Fuzzy C-means (FCM). The proposed method has been developed in this research in order to construct hybrid method between (HMRF) and threshold. These methods have been applied on 4 different patient data sets. The result of comparison among these methods shows that the proposed method gives good results for brain tissue detection, and is more robust and effective compared with (FCM) techniques.

  12. Impact of extraneous mispositioned events on motion-corrected brain SPECT images of freely moving animals

    SciTech Connect (OSTI)

    Angelis, Georgios I. Ryder, William J.; Bashar, Rezaul; Meikle, Steven R.; Fulton, Roger R.

    2014-09-15

    Purpose: Single photon emission computed tomography (SPECT) brain imaging of freely moving small animals would allow a wide range of important neurological processes and behaviors to be studied, which are normally inhibited by anesthetic drugs or precluded due to the animal being restrained. While rigid body motion of the head can be tracked and accounted for in the reconstruction, activity in the torso may confound brain measurements, especially since motion of the torso is more complex (i.e., nonrigid) and not well correlated with that of the head. The authors investigated the impact of mispositioned events and attenuation due to the torso on the accuracy of motion corrected brain images of freely moving mice. Methods: Monte Carlo simulations of a realistic voxelized mouse phantom and a dual compartment phantom were performed. Each phantom comprised a target and an extraneous compartment which were able to move independently of each other. Motion correction was performed based on the known motion of the target compartment only. Two SPECT camera geometries were investigated: a rotating single head detector and a stationary full ring detector. The effects of motion, detector geometry, and energy of the emitted photons (hence, attenuation) on bias and noise in reconstructed brain regions were evaluated. Results: The authors observed two main sources of bias: (a) motion-related inconsistencies in the projection data and (b) the mismatch between attenuation and emission. Both effects are caused by the assumption that the orientation of the torso is difficult to track and model, and therefore cannot be conveniently corrected for. The motion induced bias in some regions was up to 12% when no attenuation effects were considered, while it reached 40% when also combined with attenuation related inconsistencies. The detector geometry (i.e., rotating vs full ring) has a big impact on the accuracy of the reconstructed images, with the full ring detector being more advantageous. Conclusions: Motion-induced inconsistencies in the projection data and attenuation/emission mismatch are the two main causes of bias in reconstructed brain images when there is complex motion. It appears that these two factors have a synergistic effect on the qualitative and quantitative accuracy of the reconstructed images.

  13. SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

    SciTech Connect (OSTI)

    Sahoo, N; Zhu, X; Zhang, X; Poenisch, F; Li, H; Wu, R; Lii, M; Umfleet, W; Gillin, M; Mahajan, A; Grosshans, D

    2014-06-01

    Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-case dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.

  14. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro

    SciTech Connect (OSTI)

    Zhang, Huiying; Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 ; Newman, Donna R.; Bonner, James C.; Sannes, Philip L.

    2012-11-15

    Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium. The goal of this study was to define the role 6-O-sulfate plays in cellular responses to cadmium exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG side chains. Results showed that cadmium decreased cell viability and activated apoptosis pathways at low concentrations in hAT2 cells but not in the cancer cells. HSulf-1 over-expression, on the contrary, decreased cell viability and activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When combined with cadmium, HSulf-1 over-expression further decreased cell viability and exacerbated the activation of apoptosis pathways in the transformed cells but did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes these cancer cells and intensifies the injury induced by cadmium suggests that 6-O-sulfate groups on HSPGs may play important roles in protection against certain environmental toxicants, such as heavy metals. -- Highlights: ? Primary human lung alveolar type 2 (hAT2) cells and H292 and A549 cells were used. ? Cadmium induced apoptosis in hAT2 cells but not in H292 or A549 cells. ? HSulf-1exacerbates apoptosis induced by cadmium in H292 and A549 but not hAT2 cells.

  15. The probability of laser caused ocular injury to the aircrew of undetected aircraft violating the exclusion zone about the airborne aura LIDAR.

    SciTech Connect (OSTI)

    Augustoni, Arnold L.

    2006-12-01

    The probability of a laser caused ocular injury, to the aircrew of an undetected aircraft entering the exclusion zone about the AURA LIDAR airborne platform with the possible violation of the Laser Hazard Zone boundary, was investigated and quantified for risk analysis and management.

  16. Type B Accident Investigation of the Subcontractor Employee Injuries from a November 15, 2000, Fall Accident at the Oak Ridge National Laboratory

    Broader source: Energy.gov [DOE]

    On November 15, 2000, an accident occurred at the U. S. Department of Energy (DOE) Oak Ridge National Laboratory located in Oak Ridge, Tennessee. An employee of Decon and Recovery Services of Oak Ridge, LLC (DRS), working on an Oak Ridge Operations Office (ORO) Environmental Management decommissioning and demolition project received serious injuries from a fall (approximately 13 feet) from a fixed ladder.

  17. WE-D-BRE-03: Late Toxicity Following Photon Or Proton Radiotherapy in Patients with Brain Tumors

    SciTech Connect (OSTI)

    Munbodh, R; Ding, X; Yin, L; Anamalayil, S; Dorsey, J; Lustig, R; Alonso-Basanta, M

    2014-06-15

    Purpose: To identify indicators of Late Grade 3 (LG3) toxicity, late vision and hearing changes in patients treated for primary brain tumors with photon (XRT) or proton radiotherapy (PRT). Methods: We retrospectively reviewed 102 patients who received brain XRT or PRT to doses of 54 or 59.6 Gy in daily fractions of 1.8–2 Gy. Of the 80 patients (34 XRT, 39 PRT and 7 both modalities) reviewed for indicators of LG3 toxicity, 25 developed LG3 toxicity 90 to 500 days after radiotherapy completion. 55 patients had less than LG3 toxicity > 500 days after treatment. In that time, late vision and hearing changes were seen in 44 of 75 and 25 of 78 patients, respectively. The correlation between late toxicity and prescription dose, planning target volume (PTV) size, and doses to the brainstem, brain, optic chiasm, optic nerves, eyes and cochlea was evaluated. A two-tailed Fisher's exact test and Wilcoxon rank sum test were used for the statistical analysis for XRT, PRT and all patients combined. Results: Exceeding the 54 Gy-5% dose-volume brainstem constraint, but not the optic structure constraints, was significantly correlated (p < 0.05) with late vision changes in all three groups. Exceeding maximum and mean cochlear doses of 45 and 30 Gy, respectively, was a significant indicator of hearing changes (p < 0.05) in PRT patients and all patients combined. In a sub-group of 52 patients in whom the brain was contoured, the absolute brain volume receiving ≤ 50 Gy and > 60 Gy was significantly larger in patients with LG3 toxicity for all patients combined (p < 0.05). Prescription dose, brainstem dose and PTV volume were not correlated to LG3 toxicity. Conclusion: Our results indicate the importance of minimizing the brain volume irradiated, and brainstem and cochlea doses to reduce the risk of late toxicities following brain radiotherapy.

  18. Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

    SciTech Connect (OSTI)

    Minniti, Giuseppe; Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli ; Esposito, Vincenzo; Clarke, Enrico; Scaringi, Claudia; Lanzetta, Gaetano; Salvati, Maurizio; Neurosurgery Unit, Umberto I Hospital, University “Sapienza,” Rome ; Raco, Antonino; Bozzao, Alessandro; Maurizi Enrici, Riccardo

    2013-07-15

    Purpose: To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Methods and Materials: Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm{sup 3} (range, 12.6-35.7 cm{sup 3}). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death, performance measurements, and toxicity of treatment. Results: With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%). Conclusions: Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.

  19. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    SciTech Connect (OSTI)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  20. SU-E-J-171: Surface Imaging Based Intrafraction Motion Assessments for Whole Brain Radiotherapy

    SciTech Connect (OSTI)

    Wiant, D; Vanderstraeten, C; Maurer, J; Pursley, J; Terrell, J; Sintay, B

    2014-06-01

    Purpose: To quantify and characterize intrafraction motion for whole brain radiotherapy treatments in open face masks using 3D surface imaging. Methods: Fifteen whole brain patients were monitored with 3D surface imaging over a total of 202 monitoring sessions. Mean translations and rotations were calculated over each minute, each session, and over all sessions combined. The percentage of each session that the root mean square (RMS) of the linear translations were outside of 2 mm, 3 mm, 4 mm, and 5 mm were determined for each patient. Correlations between mean translations per minute and time and between standard deviation per minute and time were evaluated using Pearson's r value. Results: The mean RMS translation averaged over all patients was 1.45 mm +/− 1.52 mm. The patients spent an average of 18%, 10%, 6%, and 3% of the monitoring time outside of 2 mm, 3 mm, 4 mm, and 5 mm RMS tolerances, respectively. The RMS values averaged over all patients were 1.31 mm +/− 0.98 mm, 1.52 +/- 1.04, and 1.30 mm +/− 0.71 mm over the 1th, 5th, and 10th minutes of monitoring, respectively. Neither, the RMS values (p = 0.15) or the standard deviations of the RMS values (p = 0.16) showed significant correlations with time. Conclusion: The patients were positioned within 2 mm of isocenter, which was the initial set-up tolerance, for the majority of their treatments. The average position changed by < 0.3 mm over 10 minutes of monitoring. Short term movements, reflected by the standard deviations, where on the order of 1 mm. This immobilization system provides adequate immobilization over a course of treatment for whole brain radiotherapy. This system may also be suitable for head and neck or stereotactic radiosurgery treatments as well.

  1. Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect (OSTI)

    Yamamoto, Masaaki; Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo ; Kawabe, Takuya; Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto ; Higuchi, Yoshinori; Sato, Yasunori; Nariai, Tadashi; Barfod, Bierta E.; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-01-01

    Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume {<=}10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases treated with GKRS because the risk of complications long after treatment is not insignificant. However, even when delayed complications occur, favorable outcomes can be expected with timely neurosurgical intervention.

  2. High School Students Gear Up for Battle of the Brains - News Releases |

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NREL High School Students Gear Up for Battle of the Brains February 3, 2003 Golden, CO. - In what part of the chloroplast is carbon fixed during the Calvin cycle? Yellow fever is transmitted by what genus of mosquito? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 8 at the Colorado School of Mines in Golden. Thirty-nine teams from across the state will compete in this

  3. High School Students Gear Up for Battle of the Brains - News Releases |

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NREL High School Students Gear Up for Battle of the Brains January 30, 2004 Golden, Colo. - The Andes Mountains of South America were formed at what kind of margin? How many prime numbers are there between 30 and 60? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 7 at the Colorado School of Mines in Golden. Forty teams will compete in this rapid-fire

  4. High spatial resolution brain functional MRI using submillimeter balanced steady-state free precession acquisition

    SciTech Connect (OSTI)

    Wu, Pei-Hsin; Chung, Hsiao-Wen; Tsai, Ping-Huei; Wu, Ming-Long; Chuang, Tzu-Chao; Shih, Yi-Yu; Huang, Teng-Yi

    2013-12-15

    Purpose: One of the technical advantages of functional magnetic resonance imaging (fMRI) is its precise localization of changes from neuronal activities. While current practice of fMRI acquisition at voxel size around 3 3 3 mm{sup 3} achieves satisfactory results in studies of basic brain functions, higher spatial resolution is required in order to resolve finer cortical structures. This study investigated spatial resolution effects on brain fMRI experiments using balanced steady-state free precession (bSSFP) imaging with 0.37 mm{sup 3} voxel volume at 3.0 T. Methods: In fMRI experiments, full and unilateral visual field 5 Hz flashing checkerboard stimulations were given to healthy subjects. The bSSFP imaging experiments were performed at three different frequency offsets to widen the coverage, with functional activations in the primary visual cortex analyzed using the general linear model. Variations of the spatial resolution were achieved by removing outerk-space data components. Results: Results show that a reduction in voxel volume from 3.44 3.44 2 mm{sup 3} to 0.43 0.43 2 mm{sup 3} has resulted in an increase of the functional activation signals from (7.7 1.7)% to (20.9 2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images, leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at high spatial resolution. Activation signals aligning nicely with gray matter sulci at high spatial resolution would, on the other hand, have possibly been mistaken as noise at low spatial resolution. Conclusions: It is concluded that the bSSFP sequence is a plausible technique for fMRI investigations at submillimeter voxel widths without compromising fCNR. The reduction of partial volume averaging with nonactivated brain tissues to retain fCNR is uniquely suitable for high spatial resolution applications such as the resolving of columnar organization in the brain.

  5. NREL: News - High School Students Gear Up for Battle of the Brains

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    High School Students Gear Up for Battle of the Brains Golden, Colo., Feb. 05, 2002 What does URL stand for? What is the term for the movement of minerals and chemical compounds within a plant? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 9 at the Colorado School of Mines in Golden. Forty student teams from across the state will compete in this rapid-fire

  6. Patterns of Practice of Palliative Radiotherapy in Africa, Part 1: Bone and Brain Metastases

    SciTech Connect (OSTI)

    Sharma, Vinay Gaye, Papa Macoumba M.Med.; Wahab, Sherif Abdel; Ndlovu, Ntokozo; Ngoma, Twalib; Vanderpuye, Verna; Sowunmi, Anthonia; Kigula-Mugambe, Joseph; Jeremic, Branislav

    2008-03-15

    Purpose: To provide data on the pattern of practice of palliative radiotherapy (RT) on the African continent. Methods and Materials: A questionnaire was distributed to participants in a regional training course of the International Atomic Energy Agency in palliative cancer care and sent by e-mail to other institutions in Africa. Requested information included both infrastructure and human resources available and the pattern of RT practice for metastatic and locally advanced cancers. Results: Of 35 centers contacted, 24 (68%) completed the questionnaire. Although RT is used by most centers for most metastatic cancers, liver and lung metastases are treated with chemotherapy. Of 23 centers, 14 (61%) had a single RT regimen as an institutional policy for treating painful bone metastases, but only 5 centers (23%) of 23 used 8 Gy in 1 fraction. Brain metastases were being treated by RT to the whole brain to 30 Gy in 10 fractions, either exclusively (n = 13, 56%) or in addition to the use of 20 Gy in 5 fractions (n = 3, 14%). Conclusion: Radiotherapy is a major component of treatment of cancer patients in African countries. There is consensus among few centers for treatment schedules for almost all sites regarding time and dose-fractionation characteristics of RT regimens used and/or indications for the use of RT in this setting.

  7. Efficient block processing of long duration biotelemetric brain data for health care monitoring

    SciTech Connect (OSTI)

    Soumya, I.; Zia Ur Rahman, M.; Rama Koti Reddy, D. V.; Lay-Ekuakille, A.

    2015-03-15

    In real time clinical environment, the brain signals which doctor need to analyze are usually very long. Such a scenario can be made simple by partitioning the input signal into several blocks and applying signal conditioning. This paper presents various block based adaptive filter structures for obtaining high resolution electroencephalogram (EEG) signals, which estimate the deterministic components of the EEG signal by removing noise. To process these long duration signals, we propose Time domain Block Least Mean Square (TDBLMS) algorithm for brain signal enhancement. In order to improve filtering capability, we introduce normalization in the weight update recursion of TDBLMS, which results TD-B-normalized-least mean square (LMS). To increase accuracy and resolution in the proposed noise cancelers, we implement the time domain cancelers in frequency domain which results frequency domain TDBLMS and FD-B-Normalized-LMS. Finally, we have applied these algorithms on real EEG signals obtained from human using Emotive Epoc EEG recorder and compared their performance with the conventional LMS algorithm. The results show that the performance of the block based algorithms is superior to the LMS counter-parts in terms of signal to noise ratio, convergence rate, excess mean square error, misadjustment, and coherence.

  8. WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

    SciTech Connect (OSTI)

    Dorand, JE; Bourland, JD; Burnett, LR; Tytell, M

    2014-06-15

    Purpose: To determine dosimetric character for a custom-built Sr-90 beta irradiator designed for the study of Cutaneous Radiation Injury (CRI) in a porcine animal model. In the event of a radiological accident or terrorist event, Sr-90, a fission by-product, will likely be produced. CRI is a main concern due to the low energy and superficial penetration in tissue of beta particles from Sr-90. Seven 100 mCi plaque Sr-90 radiation sources within a custom-built irradiation device create a 40 mm diameter region of radiation-induced skin injury as part of a larger project to study the efficacy of a topical keratin-based product in CRI healing. Methods: A custom-built mobile irradiation device was designed and implemented for in vivo irradiations. Gafchromic EBT3 radiochromic film and a PTW Markus chamber type 23343 were utilized for dosimetric characterization of the beta fluence at the surface produced by this device. Films were used to assess 2-dimensional dose distribution and percent depth dose characteristics of the radiation field. Ion chamber measurements provided dose rate data within the field. Results: The radiation field produced by the irradiation device is homogeneous with high uniformity (?5%) and symmetry (?3%) with a steep dose fall-off with depth from the surface. Dose rates were determined to be 3.8 Gy/min and 3.3 Gy/min for film and ion chamber measurements, respectively. A dose rate of 3.4 Gy/min was used to calculate irradiation times for in vivo irradiations. Conclusion: The custom-built irradiation device enables the use of seven Sr-90 beta sources in an array to deliver a 40 mm diameter area of homogeneous skin dose with a dose rate that is useful for research purposes and clinically relevant for the induction of CRI. Doses of 36 and 42 Gy successfully produce Grade III CRI and are used in the study of the efficacy of KeraStat. This project has been funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No. HHSO100201200007C.

  9. Tumor Bed Dynamics After Surgical Resection of Brain Metastases: Implications for Postoperative Radiosurgery

    SciTech Connect (OSTI)

    Jarvis, Lesley A.; Simmons, Nathan E.; Bellerive, Marc; Erkmen, Kadir; Eskey, Clifford J.; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Hartford, Alan C.

    2012-11-15

    Purpose: To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). Methods and Materials: Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed {<=}1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. Results: The mean tumor volume before surgery was 14.23 cm{sup 3}, and the mean cavity volume was 8.53 cm{sup 3} immediately after surgery and 8.77 cm{sup 3} before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of {<=}2 cm{sup 3}; 10 cavities (23.3%) collapsed by >2 cm{sup 3}; and 13 cavities (30.2%) increased by >2 cm{sup 3}. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. Conclusions: In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi-institutional trial will provide more guidance to the optimal timing of cavity SRS.

  10. Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases

    SciTech Connect (OSTI)

    Likhacheva, Anna; Pinnix, Chelsea C. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Parikh, Neil R. [Baylor College of Medicine, Houston, Texas (United States)] [Baylor College of Medicine, Houston, Texas (United States); Allen, Pamela K.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chiu, Max S. [University of Nebraska-Lincoln, Lincoln, Nebraska (United States)] [University of Nebraska-Lincoln, Lincoln, Nebraska (United States); Sulman, Erik P.; Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guha-Thakurta, Nandita [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Prabhu, Sujit S. [Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cahill, Daniel P. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States)] [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Luo, Dershan; Shiu, Almon S. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L., E-mail: eric.chang@med.usc.edu [Department of Radiation Oncology, University of Southern California, Los Angeles, Los Angeles, California (United States)

    2013-03-01

    Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm{sup 3} (HR, 1.98; P<.001), age ?60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm{sup 3}). The number of BM was not predictive of DBF, LC, or OS. Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT.

  11. A Phase 2 Trial of Stereotactic Radiosurgery Boost After Surgical Resection for Brain Metastases

    SciTech Connect (OSTI)

    Brennan, Cameron; Yang, T. Jonathan; Hilden, Patrick; Zhang, Zhigang; Chan, Kelvin; Yamada, Yoshiya; Chan, Timothy A.; Lymberis, Stella C.; Narayana, Ashwatha; Tabar, Viviane; Gutin, Philip H.; Ballangrud, se; Lis, Eric; Beal, Kathryn

    2014-01-01

    Purpose: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ?18 years, and Karnofsky performance status (KPS) ?70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). Results: The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (?3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). Conclusions: Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors ?3 cm with superficial dural/pial involvement demonstrate the highest risk of LF.

  12. Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

    SciTech Connect (OSTI)

    Ma, Lijun; Sahgal, Arjun; Larson, David A.; Pinnaduwage, Dilini; Fogh, Shannon; Barani, Igor; Nakamura, Jean; McDermott, Michael; Sneed, Penny

    2014-05-01

    Purpose: To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. Methods and Materials: A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Results: Confirmatory correlation between the nominal target radius (ie, R{sub T}) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/R{sub T}, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R{sup 2} >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/R{sub T} values for the target. Conclusions: Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.

  13. SU-D-BRD-06: Automated Population-Based Planning for Whole Brain Radiation Therapy

    SciTech Connect (OSTI)

    Schreibmann, E; Fox, T; Crocker, I; Shu, H

    2014-06-01

    Purpose: Treatment planning for whole brain radiation treatment is technically a simple process but in practice it takes valuable clinical time of repetitive and tedious tasks. This report presents a method that automatically segments the relevant target and normal tissues and creates a treatment plan in only a few minutes after patient simulation. Methods: Segmentation is performed automatically through morphological operations on the soft tissue. The treatment plan is generated by searching a database of previous cases for patients with similar anatomy. In this search, each database case is ranked in terms of similarity using a customized metric designed for sensitivity by including only geometrical changes that affect the dose distribution. The database case with the best match is automatically modified to replace relevant patient info and isocenter position while maintaining original beam and MLC settings. Results: Fifteen patients were used to validate the method. In each of these cases the anatomy was accurately segmented to mean Dice coefficients of 0.970 ± 0.008 for the brain, 0.846 ± 0.009 for the eyes and 0.672 ± 0.111 for the lens as compared to clinical segmentations. Each case was then subsequently matched against a database of 70 validated treatment plans and the best matching plan (termed auto-planned), was compared retrospectively with the clinical plans in terms of brain coverage and maximum doses to critical structures. Maximum doses were reduced by a maximum of 20.809 Gy for the left eye (mean 3.533), by 13.352 (1.311) for the right eye, and by 27.471 (4.856), 25.218 (6.315) for the left and right lens. Time from simulation to auto-plan was 3-4 minutes. Conclusion: Automated database- based matching is an alternative to classical treatment planning that improves quality while providing a cost—effective solution to planning through modifying previous validated plans to match a current patient's anatomy.

  14. Materials for Stretchable Electronics - Electronic Eyeballs, Brain Monitors and Other Applications

    ScienceCinema (OSTI)

    Rogers, John A. [University of Illinois, Urbana Champaign, Illinois, United States

    2010-01-08

    Electronic circuits that involve transistors and related components on thin plastic sheets or rubber slabs offer mechanical properties (e.g. bendability, stretchability) and other features (e.g. lightweight, rugged construction) which cannot be easily achieved with technologies that use rigid, fragile semiconductor wafer or glass substrates.  Device examples include personal or structural health monitors and electronic eye imagers, in which the electronics must conform to complex curvilinear shapes or flex/stretch during use.  Our recent work accomplishes these technology outcomes by use of single crystal inorganic nanomaterials in ?wavy? buckled configurations on elastomeric supports.  This talk will describe key fundamental materials and mechanics aspects of these approaches, as well as engineering features of their use in individual transistors, photodiodes and integrated circuits.  Cardiac and brain monitoring devices provide examples of application in biomedicine; hemispherical electronic eye cameras illustrate new capacities for bio-inspired device design.

  15. Insight in the Brain: The Cognitive and Neural Bases of Eureka Moments

    SciTech Connect (OSTI)

    Beeman, Mark

    2013-04-03

    Where do new ideas come from? Although all new ideas build on old, this can happen in different ways. Some new ideas, or solutions to old problems, are achieved through methodical, analytical processing. Other new ideas come about in a sudden burst of insight, often based on or generating a restructured view of the problem itself. Behavioral, brain imaging, and eye-tracking results all reveal distinct cortical networks contributing to insight solving, as contrasted with analytic solving. Consistently, the way in which people solve problems appears to relate to the way they engage attention and cognitive control: across time, across moods, and across individuals. Insight is favored when people can disengage from strong stimuli and associations - figuratively and literally looking "outside the box" of the problem to suddenly solve with a new idea.

  16. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    SciTech Connect (OSTI)

    Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A; Kuznetsova, Jana V; Semyachkin-Glushkovskii, I A; Agafonov, Dmitry N; Tuchin, Valerii V

    2012-06-30

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  17. Brain-Emulating Cognition and Control Architecture (BECCA) v. 0.2 beta

    Energy Science and Technology Software Center (OSTI)

    2009-06-16

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains an application for controlling robot hardware through a socket. The code was created so asmore » to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one robot are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.« less

  18. MONSTIR II: A 32-channel, multispectral, time-resolved optical tomography system for neonatal brain imaging

    SciTech Connect (OSTI)

    Cooper, Robert J. Magee, Elliott; Everdell, Nick; Magazov, Salavat; Varela, Marta; Airantzis, Dimitrios; Gibson, Adam P.; Hebden, Jeremy C.

    2014-05-15

    We detail the design, construction and performance of the second generation UCL time-resolved optical tomography system, known as MONSTIR II. Intended primarily for the study of the newborn brain, the system employs 32 source fibres that sequentially transmit picosecond pulses of light at any four wavelengths between 650 and 900 nm. The 32 detector channels each contain an independent photo-multiplier tube and temporally correlated photon-counting electronics that allow the photon transit time between each source and each detector position to be measured with high temporal resolution. The system's response time, temporal stability, cross-talk, and spectral characteristics are reported. The efficacy of MONSTIR II is demonstrated by performing multi-spectral imaging of a simple phantom.

  19. In-vivo measurement of lithium in the brain and other organs

    DOE Patents [OSTI]

    Vartsky, David; Wielopolski, Lucian; LoMonte, Anthony F.; Ellis, Kenneth J.; Cohn, Stanton H.

    1985-01-01

    The lithium used clinically and distributed in organs such as the brain or idney of humans and other exhaling animals is determined in-vivo by means of neutron radiation and measuring in the exhaled air elemental tritiated hydrogen released from the tritium reaction by the reaction .sup.6 Li(n,.alpha.)T. The tritium atoms so released are transformed in part in the surrounding aqueous solution to form gaseous tritiated hydrogen which has a small solubility in body tissues and liquids and thus appears quickly in the breath. After a recipient fasts and is irradiated with neutrons, the air exhaled in the breath for a given time after irradiation is captured and processed to remove water, isolate hydrogen and measure the tritiated hydrogen with a gaseous organ-methane counter.

  20. A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

    SciTech Connect (OSTI)

    Sperduto, Paul W.; Wang, Meihua; Robins, H. Ian; Schell, Michael C.; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K.; Khuntia, Deepak; Demas, William; Shah, Sunjay A.; Nedzi, Lucien A.; Perry, Gad; Suh, John H.; Mehta, Minesh P.

    2013-04-01

    Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

  1. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  2. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    SciTech Connect (OSTI)

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  3. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    SciTech Connect (OSTI)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  4. Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

    SciTech Connect (OSTI)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Lieberson, Robert E.; Soltys, Scott G.

    2012-10-01

    Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  5. A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC

    SciTech Connect (OSTI)

    Choi, Joungil; Veterans Affairs Medical Center, Baltimore, MD 21201 ; Batchu, Vera Venkatanaresh Kumar; Veterans Affairs Medical Center, Baltimore, MD 21201 ; Schubert, Manfred; Castellani, Rudolph J.; Russell, James W.; Veterans Affairs Medical Center, Baltimore, MD 21201

    2013-06-14

    Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α isoform localizes to the mitochondrial inner membrane and matrix in brain as determined by protease protection and carbonate extraction assays, as well as by immunoelectron microscopy. Immunoelectron microscopy and import experiments in vitro revealed that 35 kDa PGC-1α colocalizes and interacts with the voltage-dependent anion channel (VDAC), and that its import depends on VDAC. Valinomycin treatment which depolarizes the membrane potential, abolished mitochondrial localization of the 35 kDa PGC-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.

  6. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    SciTech Connect (OSTI)

    Atalar, Banu; Modlin, Leslie A.; Choi, Clara Y.H.; Adler, John R.; Gibbs, Iris C.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Nagpal, Seema; Hanlon, Alexandra; Soltys, Scott G.

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  7. Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; Anchel, David J.; Gaudette, Glenn; Romanelli, Pantaleo; Hainfeld, James

    2010-06-29

    A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

  8. Defining the Optimal Planning Target Volume in Image-Guided Stereotactic Radiosurgery of Brain Metastases: Results of a Randomized Trial

    SciTech Connect (OSTI)

    Kirkpatrick, John P.; Wang, Zhiheng; Sampson, John H.; McSherry, Frances; Herndon, James E.; Allen, Karen J.; Duffy, Eileen; Hoang, Jenny K.; Chang, Zheng; Yoo, David S.; Kelsey, Chris R.; Yin, Fang-Fang

    2015-01-01

    Purpose: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. Methods and Materials: Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board–approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator–based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). Results: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non–small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed. Conclusions: SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate.

  9. Evaluation of the Dopamine Hypothesis of ADHD with PET Brain Imaging

    ScienceCinema (OSTI)

    Swanson, James [University of California, Irvine, California, United States

    2010-09-01

    The Dopamine (DA) Hypothesis of ADHD (Wender, 1971; Levy, 1990) suggests that abnormalities in the synaptic mechanisms of DA transmission may be disrupted, and specific abnormalities in DA receptors and DA transporters (DAT) have been proposed (see Swanson et al, 1998). Early studies with small samples (e.g., n = 6, Dougherty et al, 1999) used single photon emission tomography (SPECT) and the radioligand (123I Altropane) to test a theory that ADHD may be caused by an over expression of DAT and reported 'a 70% increase in age-corrected dopamine transporter density in patients with attention deficit hyperactivity disorder compared with healthy controls' and suggested that treatment with stimulant medication decreased DAT density in ADHD patients and corrected an underlying abnormality (Krause et al, 2000). The potential importance of these findings was noted by Swanson (1999): 'If true, this is a major finding and points the way for new investigations of the primary pharmacological treatment for ADHD (with the stimulant drugs - e.g., methylphenidate), for which the dopamine transporter is the primary site of action. The potential importance of this finding demands special scrutiny'. This has been provided over the past decade using Positron Emission Tomography (PET). Brain imaging studies were conducted at Brookhaven National Laboratory (BNL) in a relatively large sample of stimulant-naive adults assessed for DAT (11C cocaine) density and DA receptors (11C raclopride) availability. These studies (Volkow et al, 2007; Volkow et al, 2009) do not confirm the hypothesis of increased DAT density and suggest the opposite (i.e., decreased rather than increased DAT density), and follow-up after treatment (Wang et al, 2010) does not confirm the hypothesis that therapeutic doses of methylphenidate decrease DAT density and suggests the opposite (i.e., increased rather than decreased DAT density). The brain regions implicated by these PET imaging studies also suggest that a motivation deficit may contribute as much as an attention deficit to the manifestation of behaviors that underlie the symptoms of ADHD.

  10. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect (OSTI)

    Sunil, Vasanthi R.; Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS ?/? mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS ?/? mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS ?/? mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS ?/? mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS ?/? mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ? Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ? RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ? iNOS ?/? mice are protected from CEES-induced lung toxicity and altered lung functioning.

  11. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    SciTech Connect (OSTI)

    Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

    2014-09-26

    Highlights: Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. Nicaraven enhanced the function of hematopoietic stem/progenitor cells. Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy ?-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose ?-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy ?-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 6090% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  12. Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis.

    SciTech Connect (OSTI)

    Piehowski, Paul D.; Petyuk, Vladislav A.; Orton, Daniel J.; Xie, Fang; Moore, Ronald J.; Ramirez Restrepo, Manuel; Engel, Anzhelika; Lieberman, Andrew P.; Albin, Roger L.; Camp, David G.; Smith, Richard D.; Myers, Amanda J.

    2013-05-03

    To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE clean-up (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) >> instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its suitability for discovery proteomics studies is demonstrated.

  13. X and Y chromosome behavior in brain tumors: Pieces in a puzzle

    SciTech Connect (OSTI)

    Hecht, B.K. [Hecht Associates, Jacksonville, FL (United States); Chatel, M; Gioanni, J. [Univ. of Nice (France)] [and others

    1994-09-01

    Sex chromosome behavior in selected somatic cells is baffling. We serendipitously encountered this sex chromosome shuffle while studying malignant gliomas. Tumor specimens from 3/10 (30%) females and 15/27 (56%) males had sex chromosome abnormalities. Specimens from females showed X loss in 2 cases and possible X gain in 1 case. In 2 cases with autosomal abnormalities, only XX cells were found, suggesting that sex chromosome changes are independent of autosomal changes. Specimens from males showed Y rearrangements in 3 cases, Y loss in 15 cases, XX in 3 cases and autosomal abnormalities in 9 cases. The Y rearrangements may provide a route to Y loss whereas the advent of XX clones in male tumors bespeaks X isodisomy, a mechanism for adding an extra active X. The autosomal changes were rearrangements against a pseudo-diploid background in 5 cases and near-triploidy/tetraploidy in 4 cases. The cases with autosomal changes tended not to have sex chromosome abnormalities (p<0.01) and, the converse, cases with sex chromosome anomalies were without autosomal abnormalities (p<0.05). The process of sex chromosome changes appears independent of the process of autosomal changes. The conventional interpretation: the sex chromosome changes in brain tumors are in non-malignant cells. An unconventional interpretation: sex chromosome changes represent an alternative avenue to malignancy.

  14. Systematic Optimization of Long Gradient Chromatography Mass Spectrometry for Deep Analysis of Brain Proteome

    SciTech Connect (OSTI)

    Wang, Hong; Yang, Yanling; Li, Yuxin; Bai, Bing; Wang, Xusheng; Tan, Haiyan; Liu, Tao; Beach, Thomas G.; Peng, Junmun; Wu, Zhiping

    2015-02-06

    Development of high resolution liquid chromatography (LC) is essential for improving the sensitivity and throughput of mass spectrometry (MS)-based proteomics. Here we present systematic optimization of a long gradient LC-MS/MS platform to enhance protein identification from a complex mixture. The platform employed an in-house fabricated, reverse phase column (100 μm x 150 cm) coupled with Q Exactive MS. The column was capable of achieving a peak capacity of approximately 700 in a 720 min gradient of 10-45% acetonitrile. The optimal loading level was about 6 micrograms of peptides, although the column allowed loading as many as 20 micrograms. Gas phase fractionation of peptide ions further increased the number of peptide identification by ~10%. Moreover, the combination of basic pH LC pre-fractionation with the long gradient LC-MS/MS platform enabled the identification of 96,127 peptides and 10,544 proteins at 1% protein false discovery rate in a postmortem brain sample of Alzheimer’s disease. As deep RNA sequencing of the same specimen suggested that ~16,000 genes were expressed, current analysis covered more than 60% of the expressed proteome. Further improvement strategies of the LC/LC-MS/MS platform were also discussed.

  15. Brain-Emulating Cognition and Control Architecture (BECCA) V1.0 beta

    Energy Science and Technology Software Center (OSTI)

    2007-09-30

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains two simulations of BECCA controlling robots: one is a one degree-of-freedom spinner robot and themore » other is a 7 degree-of-freedom serial link arm with a terminal gripper. In addition, the software contains code that identifies synonyms in a untagged corpus of ASCII words. This last is a demonstration of BECCA's ability to generate abstract concepts from concrete experience. The BECCA simulation is coded so as to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one simulation are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.« less

  16. Accident Investigation of the February 7, 2013, Scissor Lift Accident in the West Hackberry Brine Tank-14 Resulting in Injury, Strategic Petroleum Reserve West Hackberry, LA

    Broader source: Energy.gov [DOE]

    On February 15, 2013, an Accident Investigation Board (the Board) was appointed to investigate an accident that resulted in serious injuries caused when a scissor lift tipped over in Brine Tank-14 (WHT-14) at the Strategic Petroleum Reserve, West Hackberry, Louisiana, site on February 7, 2013. The Board’s responsibilities have been completed with respect to this investigation. The analysis and the identification of the direct cause, root causes, contributing causes, and judgments of need resulting from this investigation were performed in accordance with the Department of Energy (DOE) Order 225.1B, Accident Investigations.

  17. U.S. Department of Energy Office of Health, Safety and Security Illness and Injury Surveillance Program Worker Health at a Glance, 2000-2009

    SciTech Connect (OSTI)

    2013-01-23

    The Worker Health at a Glance, 2000 2009 provides an overview of selected illness and injury patterns among the current DOE contractor workforce that have emerged over the 10-years covered by this report. This report is a roll-up of data from 16 individual DOE sites, assigned to one of three program offices (Office of Environmental Management, Office of Science and the National Nuclear Security Administration). In this report, an absences is defined as 40 or more consecutive work hours (5+ calendar days) off the job. Shorter absences were not included.

  18. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    SciTech Connect (OSTI)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  19. SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

    SciTech Connect (OSTI)

    Grams, M; Wilson, Z; Sio, T; Beltran, C; Tryggestad, E; Gupta, S; Blackwell, C; McCollough, K; Sarkaria, J; Furutani, K

    2014-06-01

    Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons from a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra.

  20. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques

    SciTech Connect (OSTI)

    Carey, Stephen A.; Minard, Kevin R.; Trease, Lynn L.; Wagner, James G.; Garcia, Guilherme M.; Ballinger, Carol A.; Kimbell, Julia; Plopper, Charles G.; Corley, Rick A.; Postlewait, Ed; Harkema, Jack R.

    2007-03-01

    ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.

  1. Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

    SciTech Connect (OSTI)

    Pulsifer, Margaret B.; Sethi, Roshan V.; Kuhlthau, Karen A.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

    2015-10-01

    Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.

  2. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    SciTech Connect (OSTI)

    Xu Zhiyuan; Marko, Nicholas F.; Chao, Sam T.; Angelov, Lilyana; Vogelbaum, Michael A.; Suh, John H.; Barnett, Gene H.; Weil, Robert J.

    2012-04-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  3. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

  4. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: Developmental exposure of rats to 4-methylbenzylidene camphor

    SciTech Connect (OSTI)

    Maerkel, Kirsten [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Durrer, Stefan [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Henseler, Manuel [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Schlumpf, Margret [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Lichtensteiger, Walter [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland)]. E-mail: Walter.Lichtensteiger@access.unizh.ch

    2007-01-15

    The developing neuroendocrine brain represents a potential target for endocrine active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits estrogenic activity, but also interferes with the thyroid axis. We investigated effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to the offspring until adulthood. mRNA of estrogen target genes involved in control of sexual behavior and gonadal functions was measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in a sex- and region-specific manner. In order to assess possible changes in sensitivity of target genes to estrogens, offspring were gonadectomized on day 70, injected with estradiol (E2, 10 or 50 {mu}g/kg s.c.) or vehicle on day 84, and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h) of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO, whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data indicate profound sex- and region-specific alterations in the regulation of estrogen target genes at brain level. Effect patterns in baseline and E2-induced gene expression differ from those in uterus and prostate.

  5. SU-C-9A-07: Fabrication and Calibration of a Novel High-Sensitivity Collimator for Brain SPECT Imaging

    SciTech Connect (OSTI)

    Park, M; Kijewski, M; Horky, L; Moore, S; Keijzers, M; Keijzers, R; Kalfin, L; Crough, J; Goswami, M

    2014-06-01

    Purpose: We have designed a novel collimator for brain SPECT imaging that yields greatly increased sensitivity near the center of the brain without loss of resolution. The collimator was manufactured and initial evaluation has been completed. Methods: The collimator was time-consuming and challenging to build. Because our desired hole pattern required substantial variations in hole angle, we designed two supporting plates to securely position about 34,000 hexagonal, slightly tapered, 75-mm long steel pins. The holes in the plates were modeled to yield the desired focal length, hole length and septal thickness. Molten lead was poured in between the plates, and all pins were removed after cooling. The sensitivity gain compared to a fan-beam collimator was measured using a point source placed along the central ray at several distances from the collimator face. Visual inspection of the holes was not possible as the collimator was sealed so it could be safely mounted on a SPECT system. Therefore, we prepared a 2D array of 768, ∼48μCi Tc-99m point sources, separated by 1.6 cm. The array was imaged for 10 minutes at 4 shifted locations to reduce sampling distance to 8 mm. Results: The sensitivity of the novel cone-beam collimator varied with distance from the detector face; it was higher than that of the fan-beam collimator by factors ranging from 3 to 176. Examination of the projections of the 4×768 point sources revealed that fewer than 2% of the holes were fully or partially blocked, which indicates that the intensive manual fabrication process was very successful. Conclusion: We have designed and manufactured a novel collimator for brain SPECT imaging. As expected, the sensitivity is much higher than that of a fan-beam collimator. Because of differences between the manufactured collimator and its design, reconstruction of the data will require a measured system function.

  6. A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

    SciTech Connect (OSTI)

    Karaiskos, Pantelis; Moutsatsos, Argyris; Pappas, Eleftherios; Georgiou, Evangelos; Roussakis, Arkadios; Torrens, Michael; Seimenis, Ioannis

    2014-12-01

    Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquired from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.

  7. Influence of cadmium on ketamine-induced anesthesia and brain microsomal Na[sup +], K[sup +]-ATPase in mice

    SciTech Connect (OSTI)

    Shen, Y.; Sangiah, S. )

    1994-10-01

    Cadmium is a rare metallic element, present in almost all types of food. Shellfish, wheat and rice accumulate very high amounts. Occupational and environmental pollutants are the main sources of cadmium exposure. Cadmium has a very long biologic half-life. Exposure to Cadmium causes anemia, hypertension, hepatic, renal, pulmonary and cardiovascular disorders as well as being a possible mutagen, teratogen and carcinogen. Acute cadmium treatment increased the hexobarbital sleeping time and inhibited hepatic microsomal drug metabolism due to a decrease in cytochrome P[sub 450] content. Cadmium potentiated ethanol-induced sleep in a dose-dependent manner. Cadmium has been shown to inhibit brain microsomal Na[sup +], K[sup +]-ATPase activity in vitro and in vivo. Cadmium and ethanol additively inhibited brain Na[sup +], K[sup +]-ATPase. This might be a direct interaction between cadmium and ethanol in the central nervous system. Ketamine is an intravenous anesthetic agent. It acts on central nervous system and produces [open quotes]dissociative anaesthesia.[close quotes] Ketamine provides adequate surgical anesthesia and is used alone in humans and/or combination with xylazine, an [alpha][sub 2]-adrenergic agonist in animals. It produces CNS depression, analgesia, amnesia, immobility and a feeling of dissociation from the environment. Ketamine is a non-competitive antagonist of the NMDA subset of the glutamate receptor. This perhaps results in an increase in neuronal activity leading to disorganization of normal neurotransmission and produces dissociative anesthetic state. Because it is different from most other anesthetics, ketamine may be expected to have a unique effect on brain biochemical parameters and enzymes. The purpose of this study was to examine the interactions between cadmium and ketamine on the central nervous system and ATPase, in an attempt to further understand the mechanism of action. 12 refs., 3 figs.

  8. Compartment modeling of dynamic brain PETThe impact of scatter corrections on parameter errors

    SciTech Connect (OSTI)

    Hggstrm, Ida Karlsson, Mikael; Larsson, Anne; Schmidtlein, C. Ross

    2014-11-01

    Purpose: The aim of this study was to investigate the effect of scatter and its correction on kinetic parameters in dynamic brain positron emission tomography (PET) tumor imaging. The 2-tissue compartment model was used, and two different reconstruction methods and two scatter correction (SC) schemes were investigated. Methods: The GATE Monte Carlo (MC) software was used to perform 2 15 full PET scan simulations of a voxelized head phantom with inserted tumor regions. The two sets of kinetic parameters of all tissues were chosen to represent the 2-tissue compartment model for the tracer 3?-deoxy-3?-({sup 18}F)fluorothymidine (FLT), and were denoted FLT{sub 1} and FLT{sub 2}. PET data were reconstructed with both 3D filtered back-projection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM). Images including true coincidences with attenuation correction (AC) and true+scattered coincidences with AC and with and without one of two applied SC schemes were reconstructed. Kinetic parameters were estimated by weighted nonlinear least squares fitting of image derived timeactivity curves. Calculated parameters were compared to the true input to the MC simulations. Results: The relative parameter biases for scatter-eliminated data were 15%, 16%, 4%, 30%, 9%, and 7% (FLT{sub 1}) and 13%, 6%, 1%, 46%, 12%, and 8% (FLT{sub 2}) for K{sub 1}, k{sub 2}, k{sub 3}, k{sub 4}, V{sub a}, and K{sub i}, respectively. As expected, SC was essential for most parameters since omitting it increased biases by 10 percentage points on average. SC was not found necessary for the estimation of K{sub i} and k{sub 3}, however. There was no significant difference in parameter biases between the two investigated SC schemes or from parameter biases from scatter-eliminated PET data. Furthermore, neither 3DRP nor OSEM yielded the smallest parameter biases consistently although there was a slight favor for 3DRP which produced less biased k{sub 3} and K{sub i} estimates while OSEM resulted in a less biased V{sub a}. The uncertainty in OSEM parameters was about 26% (FLT{sub 1}) and 12% (FLT{sub 2}) larger than for 3DRP although identical postfilters were applied. Conclusions: SC was important for good parameter estimations. Both investigated SC schemes performed equally well on average and properly corrected for the scattered radiation, without introducing further bias. Furthermore, 3DRP was slightly favorable over OSEM in terms of kinetic parameter biases and SDs.

  9. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    SciTech Connect (OSTI)

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort is planned.

  10. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    SciTech Connect (OSTI)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  11. SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

    SciTech Connect (OSTI)

    Dong, P; Ma, L

    2014-06-15

    Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution and superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to the 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.

  12. Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

    SciTech Connect (OSTI)

    Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng; Tridandapani, Srini; School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332; Winship Cancer Institute, Emory University, Atlanta, Georgia 30322 ; Beitler, Jonathan J.; Yu, David S.; Curran, Walter J.; Liu, Tian; Bruner, Deborah W.; Winship Cancer Institute, Emory University, Atlanta, Georgia 30322; School of Nursing, Emory University, Atlanta, Georgia 30322

    2014-02-15

    Purpose: The study aims to investigate whether Nakagami parametersestimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signalscould provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 9.5 Gy, and the mean follow-up time was 16.3 4.8 months. All enrolled patients experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.

  13. A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

    SciTech Connect (OSTI)

    Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

    2013-02-01

    The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

  14. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    SciTech Connect (OSTI)

    Skinner, F. K.; Department of Medicine , University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8 ; Ferguson, K. A.; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  15. Seizure control with thermal energy? Modeling of heat diffusivity in brain tissue and computer-based design of a prototype mini-cooler.

    SciTech Connect (OSTI)

    Osario, I.; Chang, F.-C.; Gopalsami, N.; Nuclear Engineering Division; Univ. of Kansas

    2009-10-01

    Automated seizure blockage is a top priority in epileptology. Lowering nervous tissue temperature below a certain level suppresses abnormal neuronal activity, an approach with certain advantages over electrical stimulation, the preferred investigational therapy for pharmacoresistant seizures. A computer model was developed to identify an efficient probe design and parameters that would allow cooling of brain tissue by no less than 21 C in 30 s, maximum. The Pennes equation and the computer code ABAQUS were used to investigate the spatiotemporal behavior of heat diffusivity in brain tissue. Arrays of distributed probes deliver sufficient thermal energy to decrease, inhomogeneously, brain tissue temperature from 37 to 20 C in 30 s and from 37 to 15 C in 60 s. Tissue disruption/loss caused by insertion of this probe is considerably less than that caused by ablative surgery. This model may be applied for the design and development of cooling devices for seizure control.

  16. Effect of acute treatment with cadmium on ethanol anesthesia, body termperature, and synaptosomal Na/sup +/-K/sup +/-ATPase of rat brain

    SciTech Connect (OSTI)

    Magour, S.; Kristof, V.; Baumann, M.; Assmann, G.

    1981-12-01

    The effect of a single intraperitoneal dose of 0.56, 1.12, and 1.68 mg cadmium/kg on the duration of ethanol-induced sleep was investigated in male rats. Cadmium potentiated ethanol sleeping time in a dose dependent manner up to 300% over controls. No significant difference in the elimination rate of ethanol from blood and brain and observed between control and cadmium-pretreated rats. Cadmium slightly inhibited the hepatic alcohol dehydrogenase in vivo and also potentiated ethanol hypothermia but these changes did not play a significant role in the observed prolongation of ethanol sleeping time. However, cadmium and ethanol additively inhibited brain synaptosomal Na/sup +/-K/sup +/-ATPase in a noncompetitive manner. The results so far indicate that cadmium may increase brain responsiveness toward ethanol partly through inhibition of snaptosomal Na/sup +/-K/sup +/-ATPase.

  17. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    SciTech Connect (OSTI)

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning systemMultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was printed using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. Conclusions: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.

  18. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    SciTech Connect (OSTI)

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. Conclusions: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.

  19. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    SciTech Connect (OSTI)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-?FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (2013%) than controls (911%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (1012%) compared to NS in both groups (1513%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.

  20. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-¹⁸FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared tomore » placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.« less

  1. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    SciTech Connect (OSTI)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-¹⁸FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.

  2. The Risk Factors of Symptomatic Communicating Hydrocephalus After Stereotactic Radiosurgery for Unilateral Vestibular Schwannoma: The Implication of Brain Atrophy

    SciTech Connect (OSTI)

    Han, Jung Ho [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of) [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr [Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee [Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of) [Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Chae-Yong [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of) [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hwang, Seung-Sik [Department of Social and Preventive Medicine, Inha University School of Medicine, Incheon (Korea, Republic of)] [Department of Social and Preventive Medicine, Inha University School of Medicine, Incheon (Korea, Republic of); Park, Jeong-Hoon [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of)] [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of); Kim, Young-Hoon [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of) [Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Jin Wook; Kim, Yong Hwy; Song, Sang Woo; Kim, In Kyung; Jung, Hee-Won [Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of) [Department of Neurosurgery, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Neurosurgery, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    Purpose: To identify the effect of brain atrophy on the development of symptomatic communicating hydrocephalus (SCHCP) after stereotactic radiosurgery (SRS) for sporadic unilateral vestibular schwannomas (VS). Methods and Materials: A total of 444 patients with VS were treated with SRS as a primary treatment. One hundred eighty-one patients (40.8%) were male, and the mean age of the patients was 53 {+-} 13 years (range, 11-81 years). The mean follow-up duration was 56.8 {+-} 35.8 months (range, 12-160 months). The mean tumor volume was 2.78 {+-} 3.33 cm{sup 3} (range, 0.03-23.30 cm{sup 3}). The cross-sectional area of the lateral ventricles (CALV), defined as the combined area of the lateral ventricles at the level of the mammillary body, was measured on coronal T1-weighted magnetic resonance images as an indicator of brain atrophy. Results: At distant follow-up, a total of 25 (5.6%) patients had SCHCP. The median time to symptom development was 7 months (range, 1-48 months). The mean CALV was 334.0 {+-} 194.0 mm{sup 2} (range, 44.70-1170 mm{sup 2}). The intraclass correlation coefficient was 0.988 (95% confidence interval [CI], 0.976-0.994; p < 0.001). In multivariate analysis, the CALV had a significant relationship with the development of SCHCP (p < 0.001; odds ration [OR] = 1.005; 95% CI, 1.002-1.007). Tumor volume and female sex also had a significant association (p < 0.001; OR = 1.246; 95% CI, 1.103-1.409; p < 0.009; OR = 7.256; 95% CI, 1.656-31.797, respectively). However, age failed to show any relationship with the development of SCHCP (p = 0.364). Conclusion: Brain atrophy may be related to de novo SCHCP after SRS, especially in female patients with a large VS. Follow-up surveillance should be individualized, considering the risk factors involved for each patient, for prompt diagnosis of SCHCP.

  3. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    SciTech Connect (OSTI)

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2?-, 3?-cyclic-nucleotide-3?-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. The attenuation in myelin and axon is synergistic. The optic nerve and brain demonstrate reduced glutamine synthetase. The retina exhibits diminished neurotrophin levels and cellular differentiation. The toxic effect is apoptotic.

  4. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    SciTech Connect (OSTI)

    Jung, Jin Ho; Choi, Yong Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

    2015-05-15

    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Conclusions: Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.

  5. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    SciTech Connect (OSTI)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-10-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

  6. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    SciTech Connect (OSTI)

    Parlak, Cem; Mertsoylu, Hüseyin; Güler, Ozan Cem; Onal, Cem; Topkan, Erkan

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  7. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

    SciTech Connect (OSTI)

    Tryndyak, Volodymyr P.; Latendresse, John R.; Montgomery, Beverly; Ross, Sharon A.; Beland, Frederick A.; Rusyn, Ivan; Pogribny, Igor P.

    2012-07-01

    MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ? Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ? The extent of liver pathology was accompanied by the changes in microRNA expression. ? The levels of circulating microRNAs mirror the magnitude of fatty liver injury. ? Plasma microRNAs may be sensitive noninvasive indicators of the fatty liver injury.

  8. Influence of a Weak Field of Pulsed DC Electricity on the Behavior and Incidence of Injury in Adult Steelhead and Pacific Lamprey, Final Report.

    SciTech Connect (OSTI)

    Mesa, Matthew

    2009-02-13

    Predation by pinnipeds, such as California sea lions Zalophus californianus, Pacific harbor seals Phoca vitulina, and Stellar sea lions Eumetopias jubatus on adult Pacific salmon Oncorhynchus spp in the lower Columbia River has become a serious concern for fishery managers trying to conserve and restore runs of threatened and endangered fish. As a result, Smith-Root, Incorporated (SRI; Vancouver, Washington), manufacturers of electrofishing and closely-related equipment, proposed a project to evaluate the potential of an electrical barrier to deter marine mammals and reduce the amount of predation on adult salmonids (SRI 2007). The objectives of their work were to develop, deploy, and evaluate a passive, integrated sonar and electric barrier that would selectively inhibit the upstream movements of marine mammals and reduce predation, but would not injure pinnipeds or impact anadromous fish migrations. However, before such a device could be deployed in the field, concerns by regional fishery managers about the potential effects of such a device on the migratory behavior of Pacific salmon, steelhead O. mykiss, Pacific lampreys Entoshpenus tridentata, and white sturgeon Acipenser transmontanus, needed to be addressed. In this report, we describe the results of laboratory research designed to evaluate the effects of prototype electric barriers on adult steelhead and Pacific lampreys. The effects of electricity on fish have been widely studied and include injury or death (e.g., Sharber and Carothers 1988; Dwyer et al. 2001; Snyder 2003), physiological dysfunction (e.g., Schreck et al. 1976; Mesa and Schreck 1989), and altered behavior (Mesa and Schreck 1989). Much of this work was done to investigate the effects of electrofishing on fish in the wild. Because electrofishing operations would always use more severe electrical settings than those proposed for the pinniped barrier, results from these studies are probably not relevant to the work proposed by SRI. Field electrofishing operations typically use high voltage and amperage settings and a variety of waveforms, pulse widths (PW), and pulse frequencies (PF), depending on conditions and target species. For example, when backpack electrofishing for trout in a small stream, one might use settings such as 500 V pulsed DC, a PW of 1 ms, and a PF of 60 Hz. In contrast, the electrical barrier proposed by SRI will produce electrical conditions significantly lower than those used in electrofishing, particularly for PW and PF (e.g., PW ranging from 300-1,000 {micro}s and PF from 2-3 Hz). Further, voltage gradients (in V/cm) are predicted to be lower in the electric barrier than those produced during typical electrofishing. Although the relatively weak, pulsed DC electric fields to be produced by the barrier may be effective at deterring pinnipeds, little, if anything, is known about the effects of such low intensity electrical fields on fish behavior. For this research, we evaluated the effects of weak, pulsed DC electric currents on the behavior of adult steelhead and Pacific lamprey and the incidence of injury in steelhead only. In a series of laboratory experiments, we: (1) documented the rate of passage of fish over miniature, prototype electric barriers when they were on and off; (2) determined some electric thresholds beyond which fish would not pass over the barrier; and (3) assessed the incidence and severity of injury in steelhead exposed to relatively severe electrical conditions. The results of this study should be useful for making decisions about whether to install electrical barriers in the lower Columbia River, or elsewhere, to reduce predation on upstream migrating salmonids and other fishes by marine pinnipeds.

  9. SU-E-J-90: MRI-Based Treatment Simulation and Patient Setup for Radiation Therapy of Brain Cancer

    SciTech Connect (OSTI)

    Yang, Y; Cao, M; Han, F; Santhanam, A; Neylon, J; Gomez, C; Kaprealian, T; Sheng, K; Agazaryan, N; Low, D; Hu, P

    2014-06-01

    Purpose: Traditional radiation therapy of cancer is heavily dependent on CT. CT provides excellent depiction of the bones but lacks good soft tissue contrast, which makes contouring difficult. Often, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks. It is desirable to perform treatment simulation entirely based on MRI. To achieve MR-based simulation for radiation therapy, bone imaging is an important challenge because of the low MR signal intensity from bone due to its ultra-short T2 and T1, which presents difficulty for both dose calculation and patient setup in terms of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate DRR using MRI with an Ultra Short Echo Time (UTE) sequence which is applicable to both OBI and ExacTrac 2D patient setup. Methods: Seven brain cancer patients were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times. The two images were processed using in-house software. The resultant bone images were subsequently loaded into commercial systems to generate DRRs. Simulation and patient clinical on-board images were used to evaluate 2D patient setup with MRI-DRRs. Results: The majority bones are well visualized in all patients. The fused image of patient CT with the MR bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of good quality. Accuracy of 2D patient setup by using MRI-DRR is comparable to CT-based 2D patient setup. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post-processing procedure to achieve robust MR bone imaging for other human sites in addition to brain.

  10. Attenuation compensation in TC-99M SPECT brain imaging: Use of attenuation maps derived from tranmission versus emission data

    SciTech Connect (OSTI)

    Pan, T.S.; Licho, R.; Penney, B.C. [Univ. of Massachusetts Mecical Center, Worcester, MA (United States)] [and others

    1994-05-01

    This study compares reconstructions of Tc-99m brain SPECT studies made using two methods of estimating the attenuation map: (1) transmission scanning, and (2) segmenting reconstructions of emission data and assigning attenuation coefficient values. A three-head SPECT system with fan beam collimators was used. Transmission scanning was performed using a line source at the focal line of a fan beam collimator right after the regular emission scan. The higher attenuation of the skull and the lower attenuation in the sinus cavities were identifiable despite the noise in the reconstructed transmission data due to: (1) the contamination of the transmission data by emission photons, (2) the maximum acquisition count rate imposed by the SPECT system, and (3) the clinical scanning time. Emission data were recorded using both photopeak and Compton scatter energy windows. Outlines of the head and the maxillary sinus could be obtained using only the Compton scatter reconstructions, whereas identifying the skull regions and the frontal sinus required the photopeak data as well. We placed appropriate linear attenuation coefficients in the soft tissue, bone, sinus and air regions (0.15,. 0.22, 0, and 0 cm{sup -1}) and blurred this attenuation map with a Gaussian kernel of about 0.2 cm standard deviation to obtain the attenuation map based on the emission data. Reconstructions were computed using the maximum likelihood expectation maximization algorithm with Siddon`s ray-tracing algorithm. Reconstructions based on the two attenuation maps were compared quantitatively on the patient data. The differences noted were quite small. These results imply that attenuation correction based on emission data alone may be adequate for Tc-99m SPECT brain imaging.

  11. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    SciTech Connect (OSTI)

    Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

    2014-09-26

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  12. SU-E-T-492: Implementing a Method for Brain Irradiation in Rats Utilizing a Commercially Available Radiosurgery Irradiator

    SciTech Connect (OSTI)

    Cates, J; Drzymala, R

    2014-06-01

    Purpose: The purpose of the study was to implement a method for accurate rat brain irradiation using the Gamma Knife Perfexion unit. The system needed to be repeatable, efficient, and dosimetrically and spatially accurate. Methods: A platform (“rat holder”) was made such that it is attachable to the Leskell Gamma Knife G Frame. The rat holder utilizes two ear bars contacting bony anatomy and a front tooth bar to secure the rat. The rat holder fits inside of the Leskell localizer box, which utilizes fiducial markers to register with the GammaPlan planning system. This method allows for accurate, repeatable setup.A cylindrical phantom was made so that film can be placed axially in the phantom. We then acquired CT image sets of the rat holder and localizer box with both a rat and the phantom. Three treatment plans were created: a plan on the rat CT dataset, a phantom plan with the same prescription dose as the rat plan, and a phantom plan with the same delivery time as the rat plan. Results: Film analysis from the phantom showed that our setup is spatially accurate and repeatable. It is also dosimetrically accurate, with an difference between predicted and measured dose of 2.9%. Film analysis with prescription dose equal between rat and phantom plans showed a difference of 3.8%, showing that our phantom is a good representation of the rat for dosimetry purposes, allowing for +/- 3mm diameter variation. Film analysis with treatment time equal showed an error of 2.6%, which means we can deliver a prescription dose within 3% accuracy. Conclusion: Our method for irradiation of rat brain has been shown to be repeatable, efficient, and accurate, both dosimetrically and spatially. We can treat a large number of rats efficiently while delivering prescription doses within 3% at millimeter level accuracy.

  13. Sandia National Laboratories: News: Publications: Lab News

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Nov. 2, 2012 Sandia tackles complex brain injury issue BRAIN POWER - Paul Taylor (5431), right, talks with John Ludwigsen (also 5431), center, and Corey Ford, a neurologist at the...

  14. DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy

    SciTech Connect (OSTI)

    Farjam, Reza; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue; Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Med Inn Building C478, Ann Arbor, Michigan 48109-5842; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109-2099

    2014-01-15

    Purpose: To develop a pharmacokinetic modelfree framework to analyze the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data for assessment of response of brain metastases to radiation therapy. Methods: Twenty patients with 45 analyzable brain metastases had MRI scans prior to whole brain radiation therapy (WBRT) and at the end of the 2-week therapy. The volumetric DCE images covering the whole brain were acquired on a 3T scanner with approximately 5 s temporal resolution and a total scan time of about 3 min. DCE curves from all voxels of the 45 brain metastases were normalized and then temporally aligned. A DCE matrix that is constructed from the aligned DCE curves of all voxels of the 45 lesions obtained prior to WBRT is processed by principal component analysis to generate the principal components (PCs). Then, the projection coefficient maps prior to and at the end of WBRT are created for each lesion. Next, a pattern recognition technique, based upon fuzzy-c-means clustering, is used to delineate the tumor subvolumes relating to the value of the significant projection coefficients. The relationship between changes in different tumor subvolumes and treatment response was evaluated to differentiate responsive from stable and progressive tumors. Performance of the PC-defined tumor subvolume was also evaluated by receiver operating characteristic (ROC) analysis in prediction of nonresponsive lesions and compared with physiological-defined tumor subvolumes. Results: The projection coefficient maps of the first three PCs contain almost all response-related information in DCE curves of brain metastases. The first projection coefficient, related to the area under DCE curves, is the major component to determine response while the third one has a complimentary role. In ROC analysis, the area under curve of 0.88 0.05 and 0.86 0.06 were achieved for the PC-defined and physiological-defined tumor subvolume in response assessment. Conclusions: The PC-defined subvolume of a brain metastasis could predict tumor response to therapy similar to the physiological-defined one, while the former is determined more rapidly for clinical decision-making support.

  15. DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy

    SciTech Connect (OSTI)

    Farjam, Reza; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue; Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Med Inn Building C478, Ann Arbor, Michigan 48109-5842; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109-2099

    2014-01-15

    Purpose: To develop a pharmacokinetic modelfree framework to analyze the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data for assessment of response of brain metastases to radiation therapy. Methods: Twenty patients with 45 analyzable brain metastases had MRI scans prior to whole brain radiation therapy (WBRT) and at the end of the 2-week therapy. The volumetric DCE images covering the whole brain were acquired on a 3T scanner with approximately 5 s temporal resolution and a total scan time of about 3 min. DCE curves from all voxels of the 45 brain metastases were normalized and then temporally aligned. A DCE matrix that is constructed from the aligned DCE curves of all voxels of the 45 lesions obtained prior to WBRT is processed by principal component analysis to generate the principal components (PCs). Then, the projection coefficient maps prior to and at the end of WBRT are created for each lesion. Next, a pattern recognition technique, based upon fuzzy-c-means clustering, is used to delineate the tumor subvolumes relating to the value of the significant projection coefficients. The relationship between changes in different tumor subvolumes and treatment response was evaluated to differentiate responsive from stable and progressive tumors. Performance of the PC-defined tumor subvolume was also evaluated by receiver operating characteristic (ROC) analysis in prediction of nonresponsive lesions and compared with physiological-defined tumor subvolumes. Results: The projection coefficient maps of the first three PCs contain almost all response-related information in DCE curves of brain metastases. The first projection coefficient, related to the area under DCE curves, is the major component to determine response while the third one has a complimentary role. In ROC analysis, the area under curve of 0.88 ± 0.05 and 0.86 ± 0.06 were achieved for the PC-defined and physiological-defined tumor subvolume in response assessment. Conclusions: The PC-defined subvolume of a brain metastasis could predict tumor response to therapy similar to the physiological-defined one, while the former is determined more rapidly for clinical decision-making support.

  16. Evidence that formulations of the selective MAO-B inhibitor, selegiline, which bypass first-pass metabolism, also inhibit MAO-A in the human brain

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Fowler, Joanna S.; Logan, Jean; Volkow, Nora D.; Shumay, Elena; McCall-Perez, Fred; Gilmor, Michelle; Jayne, Millard; Wang, Gene-Jack; Alexoff, David L.; Apelskog-Torres, Karen; et al

    2015-10-29

    Selegiline (L-deprenyl) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) at the conventional dose (10 mg/day oral) that is used in the treatment of Parkinson’s disease. However, controlled studies have demonstrated antidepressant activity for high doses of oral selegiline and for transdermal selegiline suggesting that when plasma levels of selegiline are elevated, brain MAO-A might also be inhibited. Zydis selegiline (Zelapar®) is an orally disintegrating formulation of selegiline, which is absorbed through the buccal mucosa producing higher plasma levels of selegiline and reduced amphetamine metabolites compared to equal doses of conventional selegiline. Although there is indirect evidence thatmore » Zydis selegiline at high doses loses its selectivity for MAO-B, there is no direct evidence that it also inhibits brain MAO-A in humans. We measured brain MAO-A in 18 healthy men after a 28-day treatment with Zydis selegiline (2.5, 5.0, or 10 mg/day) and in 3 subjects receiving the selegiline transdermal system (Emsam patch, 6 mg/day) using PET and the MAO-A radiotracer [¹¹C]clorgyline. We also measured dopamine transporter (DAT) availability in three subjects from the 10 mg group. The 10 mg Zydis selegiline dose significantly inhibited MAO-A (36.9 ± 19.7%, range 11–70%, p<0.007)) but not DAT; and while Emsam also inhibited MAO-A (33.2 ± 28.9 (range 9-68%) the difference did not reach significance (p=0.10)) presumably because of the small sample size. Our results provide the first direct evidence of brain MAO-A inhibition in humans by formulations of selegiline, which are currently postulated but not verified to target brain MAO-A in addition to MAO-B.« less

  17. Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

    SciTech Connect (OSTI)

    Matsunaga, Shigeo; Shuto, Takashi; Takase, Hajime; Ohtake, Makoto; Tomura, Nagatsuki; Tanaka, Takahiro; Sonoda, Masaki

    2013-01-01

    Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.

  18. Evidence that formulations of the selective MAO-B inhibitor, selegiline, which bypass first-pass metabolism, also inhibit MAO-A in the human brain

    SciTech Connect (OSTI)

    Fowler, Joanna S.; Logan, Jean; Volkow, Nora D.; Shumay, Elena; McCall-Perez, Fred; Gilmor, Michelle; Jayne, Millard; Wang, Gene-Jack; Alexoff, David L.; Apelskog-Torres, Karen; Hubbard, Barbara; Carter, Pauline; King, Payton; Fahn, Stanley; Telang, Frank; Shea, Colleen; Xu, Youwen; Muench, Lisa

    2015-10-29

    Selegiline (L-deprenyl) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) at the conventional dose (10 mg/day oral) that is used in the treatment of Parkinson’s disease. However, controlled studies have demonstrated antidepressant activity for high doses of oral selegiline and for transdermal selegiline suggesting that when plasma levels of selegiline are elevated, brain MAO-A might also be inhibited. Zydis selegiline (Zelapar®) is an orally disintegrating formulation of selegiline, which is absorbed through the buccal mucosa producing higher plasma levels of selegiline and reduced amphetamine metabolites compared to equal doses of conventional selegiline. Although there is indirect evidence that Zydis selegiline at high doses loses its selectivity for MAO-B, there is no direct evidence that it also inhibits brain MAO-A in humans. We measured brain MAO-A in 18 healthy men after a 28-day treatment with Zydis selegiline (2.5, 5.0, or 10 mg/day) and in 3 subjects receiving the selegiline transdermal system (Emsam patch, 6 mg/day) using PET and the MAO-A radiotracer [¹¹C]clorgyline. We also measured dopamine transporter (DAT) availability in three subjects from the 10 mg group. The 10 mg Zydis selegiline dose significantly inhibited MAO-A (36.9 ± 19.7%, range 11–70%, p<0.007)) but not DAT; and while Emsam also inhibited MAO-A (33.2 ± 28.9 (range 9-68%) the difference did not reach significance (p=0.10)) presumably because of the small sample size. Our results provide the first direct evidence of brain MAO-A inhibition in humans by formulations of selegiline, which are currently postulated but not verified to target brain MAO-A in addition to MAO-B.

  19. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

    SciTech Connect (OSTI)

    Sperduto, Paul W.; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

    2014-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.

  20. SU-E-T-428: Dosimetric Impact of Multileaf Collimator Leaf Width On Single and multiple Isocenter Stereotactic IMRT Treatment Plans for multiple Brain Tumors

    SciTech Connect (OSTI)

    Giem, J; Algan, O; Ahmad, S; Ali, I; Young, J; Hossain, S

    2014-06-01

    Purpose: To assess the impacts that multileaf collimator (MLC) leaf width has on the dose conformity and normal brain tissue doses of single and multiple isocenter stereotactic IMRT (SRT) plans for multiple intracranial tumors. Methods: Fourteen patients with 2–3 targets were studied retrospectively. Patients treated with multiple isocenter treatment plans using 9 to 12 non-coplanar beams per lesion underwent repeat planning using single isocenter and 10 to 12 non-coplanar beams with 2.5mm, 3mm and 5mm MLC leaf widths. Brainlab iPlan treatment planning system for delivery with the 2.5mm MLC served as reference. Identical contour sets and dose-volume constraints were applied. The prescribed dose to each target was 25 Gy to be delivered over 5 fractions with a minimum of 99% dose to cover ≥ 95% of the target volume. Results: The lesions and normal brains ranged in size from 0.11 to 51.67cc (median, 2.75cc) and 1090 to 1641cc (median, 1401cc), respectively. The Paddick conformity index for single and multiple isocenter (2.5mm vs. 3mm and 5mm MLCs) was (0.79±0.08 vs. 0.79±0.07 and 0.77±0.08) and (0.79±0.09 vs. 0.77±0.09 and 0.76±0.08), respectively. The average normal brain volumes receiving 15 Gy for single and multiple isocenter (2.5mm vs. 3mm and 5mm MLCs) were (3.65% vs. 3.95% and 4.09%) and (2.89% vs. 2.91% and 2.92%), respectively. Conclusion: The average dose conformity observed for the different leaf width for single and multiple isocenter plans were similar, throughout. However, the average normal brain volumes receiving 2.5 to 15 Gy were consistently lower for the 2.5mm MLC leaf width, especially for single isocenter plans. The clinical consequences of these integral normal brain tissue doses are still unknown, but employing the use of the 2.5mm MLC option is desirable at sparing normal brain tissue for both single and multiple isocenter cases.

  1. Institutional, Retrospective Analysis of 777 Patients With Brain Metastases: Treatment Outcomes and Diagnosis-Specific Prognostic Factors

    SciTech Connect (OSTI)

    Antoni, Delphine; Clavier, Jean-Baptiste; Pop, Marius; Schumacher, Catherine; Lefebvre, Franois; Nol, Georges

    2013-07-15

    Purpose: To retrospectively evaluate the prognostic factors and survival of a series of 777 patients with brain metastases (BM) from a single institution. Methods and Materials: Patients were treated with surgery followed by whole-brain radiation therapy (WBRT) or with WBRT alone in 16.3% and 83.7% of the cases, respectively. The patients were RPA (recursive partitioning analysis) class I, II, and III in 11.2%, 69.6%, and 18.4% of the cases, respectively; RPA class II-a, II-b, and II-c in 8.3%, 24.8%, and 66.9% of the cases, respectively; and with GPA (graded prognostic assessment) scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 in 35%, 27.5%, 18.2%, and 8.6% of the cases, respectively. Results: The median overall survival (OS) times according to RPA class I, II, and III were 20.1, 5.1, and 1.3 months, respectively (P<.0001); according to RPA class II-a, II-b, II-c: 9.1, 8.9, and 4.0 months, respectively (P<.0001); and according to GPA score 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0: 2.5, 4.4, 9.0, and 19.1 months, respectively (P<.0001). By multivariate analysis, the favorable independent prognostic factors for survival were as follows: for gastrointestinal tumor, a high Karnofsky performance status (KPS) (P=.0003) and an absence of extracranial metastases (ECM) (P=.003); for kidney cancer, few BM (P=.002); for melanoma, few BM (P=.01), an absence of ECM (P=.002), and few ECM (P=.0002); for lung cancer, age (P=.007), a high KPS (P<.0001), an absence of ECM (P<.0001), few ECM and BM (P<.0001 and P=.0006, respectively), and control of the primary tumor (P=.004); and for breast cancer, age (P=.001), a high KPS (P=.007), control of the primary tumor (P=.05), and few ECM and BM (P=.01 and P=.0002, respectively). The triple-negative subtype was a significant unfavorable factor (P=.007). Conclusion: Prognostic factors varied by pathology. Our analysis confirms the strength of prognostic factors used to determine the GPA score, including the genetic subtype for breast cancer.

  2. High-resolution single photon planar and spect imaging of brain and neck employing a system of two co-registered opposed gamma imaging heads

    DOE Patents [OSTI]

    Majewski, Stanislaw; Proffitt, James

    2011-12-06

    A compact, mobile, dedicated SPECT brain imager that can be easily moved to the patient to provide in-situ imaging, especially when the patient cannot be moved to the Nuclear Medicine imaging center. As a result of the widespread availability of single photon labeled biomarkers, the SPECT brain imager can be used in many locations, including remote locations away from medical centers. The SPECT imager improves the detection of gamma emission from the patient's head and neck area with a large field of view. Two identical lightweight gamma imaging detector heads are mounted to a rotating gantry and precisely mechanically co-registered to each other at 180 degrees. A unique imaging algorithm combines the co-registered images from the detector heads and provides several SPECT tomographic reconstructions of the imaged object thereby improving the diagnostic quality especially in the case of imaging requiring higher spatial resolution and sensitivity at the same time.

  3. Emission Computed Tomography: A New Technique for the Quantitative Physiologic Study of Brain and Heart in Vivo

    DOE R&D Accomplishments [OSTI]

    Phelps, M. E.; Hoffman, E. J.; Huang, S. C.; Schelbert, H. R.; Kuhl, D. E.

    1978-01-01

    Emission computed tomography can provide a quantitative in vivo measurement of regional tissue radionuclide tracer concentrations. This facility when combined with physiologic models and radioactively labeled physiologic tracers that behave in a predictable manner allow measurement of a wide variety of physiologic variables. This integrated technique has been referred to as Physiologic Tomography (PT). PT requires labeled compounds which trace physiologic processes in a known and predictable manner, and physiologic models which are appropriately formulated and validated to derive physiologic variables from ECT data. In order to effectively achieve this goal, PT requires an ECT system that is capable of performing truly quantitative or analytical measurements of tissue tracer concentrations and which has been well characterized in terms of spatial resolution, sensitivity and signal to noise ratios in the tomographic image. This paper illustrates the capabilities of emission computed tomography and provides examples of physiologic tomography for the regional measurement of cerebral and myocardial metabolic rate for glucose, regional measurement of cerebral blood volume, gated cardiac blood pools and capillary perfusion in brain and heart. Studies on patients with stroke and myocardial ischemia are also presented.

  4. Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

    SciTech Connect (OSTI)

    Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.; Tewatia, Dinesh; Rowley, Howard; Kuo, John S.; Khuntia, Deepak; Tome, Wolfgang A.

    2010-11-15

    Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume was 3.3 cm{sup 3}, occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy{sub 2} using helical tomotherapy and by 81% to 0.73 Gy{sub 2} using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

  5. Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

    SciTech Connect (OSTI)

    Prabhu, Roshan; Shu, Hui-Kuo; Hadjipanayis, Constantinos; Dhabaan, Anees; Hall, William; Raore, Bethwel; Olson, Jeffrey; Curran, Walter; Oyesiku, Nelson; Crocker, Ian

    2012-05-01

    Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planning target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.

  6. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    SciTech Connect (OSTI)

    Tsirulnikov, Kirill; Abuladze, Natalia; Bragin, Anatol; Brain Research Institute, University of California at Los Angeles, CA 90095 ; Faull, Kym; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095; Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 ; Cascio, Duilio; Damoiseaux, Robert; Schibler, Matthew J.; Pushkin, Alexander

    2012-09-15

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by ?-lyase. The enzymes of the GSH-conjugation pathway and ?-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a ?-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  7. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

    SciTech Connect (OSTI)

    Kito, Hiroaki; Yamazaki, Daiju; Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto; Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya ; Ohya, Susumu; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

    2011-07-29

    Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

  8. SU-D-9A-04: Brain PET/CT Imaging On a Scanner with a Large Axial Field-Of-View

    SciTech Connect (OSTI)

    Park, M; Gerbaudo, V; Hamberg, L; Seaver, K; Kijewski, M

    2014-06-01

    Purpose: Large axial field-of-view (FOV) PET/CT scanners are valued for high sensitivity. Brain PET image quality may depend on the head position within the FOV. We investigated the precision of activity estimation for brain PET imaging when the brain was positioned at the end (END) and in the middle (CEN) of the FOV. The additional CT dose for the CEN position was recorded. Methods: An image quality (Jaszczak) phantom and a striatal phantom were filled with F-18 and positioned in END and CEN locations. For each phantom and each location, we acquired a ∼1-hr listmode PET, rebinned the data into 10 frames with equal number of coincidence events, and reconstructed each frame using an iterative algorithm. For the striatal phantom, END and CEN were compared by drawing on each image three regions of interest (ROI) in axially separated uniform areas. The standard deviation of the activity estimation within each ROI was averaged over the 10 images. The coefficient of variation (CV) for activity estimation was calculated at each position. Image quality was assessed by inspecting the resolution bar pattern in the Jaszczak phantom at two different head positions. Results: The CV was the lowest for ROIs near the center of the FOV. For slices near the end, not only was the CV highest, but also the resolution pattern was degraded. CTDIvol summarized in the dose report indicated that the CT dose was ∼ 10% higher for CEN as compared to END position. Conclusion: Positioning the brain in the middle of the FOV in a large FOV PET/CT scanner allows more precise measurement of tracer uptake and better image quality at the cost of increased CT dose. For the end location longer scan times may minimize image quality degradation without any additional CT dose.

  9. A New Prognostic Index and Comparison to Three Other Indices for Patients With Brain Metastases: An Analysis of 1,960 Patients in the RTOG Database

    SciTech Connect (OSTI)

    Sperduto, Paul W. Berkey, Brian M.S.; Gaspar, Laurie E.; Mehta, Minesh; Curran, Walter

    2008-02-01

    Purpose: The purpose of this study is to introduce a new prognostic index for patients with brain metastases and compare it with three published indices. Treatment for brain metastases varies widely. A sound prognostic index is thus important to guide both clinical decision making and outcomes research. Methods and Materials: A new index was developed because of limitations in the three existing indices and new data (Radiation Therapy Oncology Group 9508) are available since the others were developed. All four indices were compared using the Radiation Therapy Oncology Group database of 1,960 patients with brain metastases from five randomized trials. The ability of the four indices to distinguish its separate classes was determined statistically. Advantages and disadvantages of each index are discussed. Results: Recursive partitioning analysis (RPA) and the new Graded Prognostic Assessment (GPA) had the most statistically significant differences between classes (p < 0.001 for all classes). Conclusions: The new index, the GPA, is as prognostic as the RPA and more prognostic than the other indices. The GPA is the least subjective, most quantitative and easiest to use of the four indices. Future clinical trials should compare the GPA with the RPA to prospectively validate these findings.

  10. 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

    SciTech Connect (OSTI)

    Lupo, Janine M., E-mail: janine.lupo@ucsf.edu [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Chuang, Cynthia F. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Chang, Susan M. [Department of Neurosurgery, University of California, San Francisco, San Francisco, CA (United States); Barani, Igor J. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Jimenez, Bert; Hess, Christopher P. [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Nelson, Sarah J. [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA (United States)

    2012-03-01

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

  11. WE-G-BRE-01: A High Power Nanotube X-Ray Microbeam Irradiator for Preclinical Brain Tumor Treatment

    SciTech Connect (OSTI)

    Chtcheprov, P; Inscoe, C; Zhang, L; Lu, J; Zhou, O; Chang, S; Sprenger, F; Laganis, P

    2014-06-15

    Purpose: Microbeam radiation therapy (MRT) is a new type of cancer treatment undergoing studies at various synchrotron facilities. The principle of MRT is using arrays of microscopically small, low-energy X-radiation for the treatment of various radio-resistant, deep-seated tumors. Our motivation is to develop a compact and inexpensive image guided MRT irradiator to use in the research lab setting. After a successful initial demonstration, here we report a second generation carbon nanotube (CNT) cathode based MRT tube, capable of producing multiple microbeam lines with an anticipated dose rate of 11 Gy/min per line. Methods: The system uses multiple line CNT source arrays to generate multiple focal lines on the anode. The increase in dose-rate, compared to our first generation system, is achieved by increasing the operating voltage from 160 kVp to 225kVp, adding multiple simultaneous focal lines on the anode, and a more efficient cooling mechanism using a 6kW oil-cooled anode. Results: This work will present the design and development process, challenges and solutions to meeting operating specifications, and the final design of the tube and collimator, along with optimization and stabilization of its use. A detailed characterization of its capabilities will be included with a comprehensive measurement of its X-ray focal line dimensions, an evaluation of its collimator alignment and microbeam dimensions, and phantom-based quantification of its dosimetric output. Conclusion: The development of a second generation, compact, multiple line MRT device using carbon nanotube (CNT) cathode based X-ray technology and a novel oil cooled anode design is presented here. With this new source, we are capable of delivering a total microbeam radiation dose comparable to the low end of the synchrotron based MRT systems for small animal brain tumor models.

  12. Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

    SciTech Connect (OSTI)

    Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

    2014-05-15

    Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

  13. High-frequency combination coding-based steady-state visual evoked potential for brain computer interface

    SciTech Connect (OSTI)

    Zhang, Feng; Zhang, Xin; Xie, Jun; Li, Yeping; Han, Chengcheng; Lili, Li; Wang, Jing; Xu, Guang-Hua

    2015-03-10

    This study presents a new steady-state visual evoked potential (SSVEP) paradigm for brain computer interface (BCI) systems. The goal of this study is to increase the number of targets using fewer stimulation high frequencies, with diminishing subject’s fatigue and reducing the risk of photosensitive epileptic seizures. The new paradigm is High-Frequency Combination Coding-Based High-Frequency Steady-State Visual Evoked Potential (HFCC-SSVEP).Firstly, we studied SSVEP high frequency(beyond 25 Hz)response of SSVEP, whose paradigm is presented on the LED. The SNR (Signal to Noise Ratio) of high frequency(beyond 40 Hz) response is very low, which is been unable to be distinguished through the traditional analysis method; Secondly we investigated the HFCC-SSVEP response (beyond 25 Hz) for 3 frequencies (25Hz, 33.33Hz, and 40Hz), HFCC-SSVEP produces n{sup n} with n high stimulation frequencies through Frequence Combination Code. Further, Animproved Hilbert-huang transform (IHHT)-based variable frequency EEG feature extraction method and a local spectrum extreme target identification algorithmare adopted to extract time-frequency feature of the proposed HFCC-SSVEP response.Linear predictions and fixed sifting (iterating) 10 time is used to overcome the shortage of end effect and stopping criterion,generalized zero-crossing (GZC) is used to compute the instantaneous frequency of the proposed SSVEP respondent signals, the improved HHT-based feature extraction method for the proposed SSVEP paradigm in this study increases recognition efficiency, so as to improve ITR and to increase the stability of the BCI system. what is more, SSVEPs evoked by high-frequency stimuli (beyond 25Hz) minimally diminish subject’s fatigue and prevent safety hazards linked to photo-induced epileptic seizures, So as to ensure the system efficiency and undamaging.This study tests three subjects in order to verify the feasibility of the proposed method.

  14. Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice

    SciTech Connect (OSTI)

    Xu, Xiaomei; Hu, Yan; Zhai, Xiaohan; Lin, Musen [Department of Pharmacology, Dalian Medical University, Dalian 116044 (China); Chen, Zhao; Tian, Xiaofeng; Zhang, Feng [Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023 (China); Gao, Dongyan; Ma, Xiaochi [Department of Pharmacology, Dalian Medical University, Dalian 116044 (China); Lv, Li, E-mail: lv_li@126.com [Department of Pharmacology, Dalian Medical University, Dalian 116044 (China); Yao, Jihong, E-mail: Yaojihong65@hotmail.com [Department of Pharmacology, Dalian Medical University, Dalian 116044 (China)

    2013-11-15

    Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-?) and tumor necrosis factor-alpha (TNF-?). Moreover, the SalA pretreatment ameliorated the increases in NF-?B and in cleaved caspase-3 caused by ConA exposure. Whereas, the pretreatment completely reversed expression of the B-cell lymphoma-extra large (Bcl-xL). More importantly, the SalA pretreatment significantly increased the expression of SIRT1, a NAD{sup +}-dependent deacetylase, which was known to attenuate acute hypoxia damage and metabolic liver diseases. In our study, the increase in SIRT1 was closely associated with down-regulation of the p66 isoform (p66shc) of growth factor adapter Shc at both protein and mRNA levels. In HepG2 cell culture, SalA pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly reversed the decreased expression of p66shc, and attenuated SalA-induced p66shc down-regulation. Collectively, the present study indicated that SalA may be a potent activator of SIRT and that SalA can alleviate ConA-induced hepatitis through SIRT1-mediated repression of the p66shc pathway. - Highlights: We report for the first time that SalA protects against ConA-induced hepatitis. We find that SalA is a potential activator of SIRT1. SalA's protection against hepatitis involves SIRT1-mediated repression of p66shc.

  15. Radiation-induced lung injury

    SciTech Connect (OSTI)

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  16. SU-E-T-542: Comparison of Stereotactic Radiosurgery (SRS) of Brain Lesions Using Gamma Knife, VMAT, IMRT, and Conformal Arcs

    SciTech Connect (OSTI)

    Li, S; Charpentier, P; Chan, P; Neicu, T; Miyamoto, C

    2014-06-01

    Purpose: To compare dose distributions in stereotactic radiation surgery of brain lesions using gamma Knife, VMAT, conformal arcs, and IMRT in order to provide an optimal treatment. Methods: Dose distributions from single shot of 4C model of Gamma Knife at the helmet collimation sizes of 4, 8, 14, and 18 mm in diameter were compared with full arcs with the square shapes of 4×4 (or 5×5), 8×8 (or 10×10), and spherical shapes of 16 or 20 mm in diameter using EDR3 films in the same gamma knife QA phantom. Plans for ten SRS cases with single and multiple lesions were created in gamma knife plans and Pinnacle plans. The external beam plans had enlarged field size by 2-mm and used single conformal full circle arc for solitary lesion and none coplanar arcs/beams for multiple lesions. Coverage, conformity index, dose to critical organs, and integral dose to the brain and nearby critical structures were compared on all plans. Structures and dose matrices were registered in a Velocity deformable image registration system. Results: Single full circle arc from Elekta beam-modulate MLC (4-mm leaf thickness) and agility MLC (5-mm leaf thickness) have larger penumbra and less flatness than that of Gamma Knife single shot. None-coplanar arcs or beams were required to achieve similar dose distribution. In general, Gamma Knife plans provided significant less integral dose than that of linac-based plans. Benefits of IMRT and VMAT versus gamma Knife and conformal arcs were not significant. Conclusion: Our dose measurement and treatment planning evaluation clearly demonstrated dose distribution differences amount current popular SRS modalities for small solitary and multiple brain lesions. The trend of using MLC shape beams or arcs to replace conventional cones should be revisited in order to keep lower integral dose if the late correlates with some radiation-induced side effects. Pilot grant from Elekta LLC.

  17. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    SciTech Connect (OSTI)

    Obeid, L; Esteve, F; Adam, J; Tessier, A; Balosso, J

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  18. SU-E-T-224: Is Monte Carlo Dose Calculation Method Necessary for Cyberknife Brain Treatment Planning?

    SciTech Connect (OSTI)

    Wang, L; Fourkal, E; Hayes, S; Jin, L; Ma, C

    2014-06-01

    Purpose: To study the dosimetric difference resulted in using the pencil beam algorithm instead of Monte Carlo (MC) methods for tumors adjacent to the skull. Methods: We retrospectively calculated the dosimetric differences between RT and MC algorithms for brain tumors treated with CyberKnife located adjacent to the skull for 18 patients (total of 27 tumors). The median tumor sizes was 0.53-cc (range 0.018-cc to 26.2-cc). The absolute mean distance from the tumor to the skull was 2.11 mm (range - 17.0 mm to 9.2 mm). The dosimetric variables examined include the mean, maximum, and minimum doses to the target, the target coverage (TC) and conformality index. The MC calculation used the same MUs as the RT dose calculation without further normalization and 1% statistical uncertainty. The differences were analyzed by tumor size and distance from the skull. Results: The TC was generally reduced with the MC calculation (24 out of 27 cases). The average difference in TC between RT and MC was 3.3% (range 0.0% to 23.5%). When the TC was deemed unacceptable, the plans were re-normalized in order to increase the TC to 99%. This resulted in a 6.9% maximum change in the prescription isodose line. The maximum changes in the mean, maximum, and minimum doses were 5.4 %, 7.7%, and 8.4%, respectively, before re-normalization. When the TC was analyzed with regards to target size, it was found that the worst coverage occurred with the smaller targets (0.018-cc). When the TC was analyzed with regards to the distance to the skull, there was no correlation between proximity to the skull and TC between the RT and MC plans. Conclusions: For smaller targets (< 4.0-cc), MC should be used to re-evaluate the dose coverage after RT is used for the initial dose calculation in order to ensure target coverage.

  19. Patch-based generation of a pseudo CT from conventional MRI sequences for MRI-only radiotherapy of the brain

    SciTech Connect (OSTI)

    Andreasen, Daniel; Van Leemput, Koen; Hansen, Rasmus H.; Andersen, Jon A. L.; Edmund, Jens M.

    2015-04-15

    Purpose: In radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, the information on electron density must be derived from the MRI scan by creating a so-called pseudo computed tomography (pCT). This is a nontrivial task, since the voxel-intensities in an MRI scan are not uniquely related to electron density. To solve the task, voxel-based or atlas-based models have typically been used. The voxel-based models require a specialized dual ultrashort echo time MRI sequence for bone visualization and the atlas-based models require deformable registrations of conventional MRI scans. In this study, we investigate the potential of a patch-based method for creating a pCT based on conventional T{sub 1}-weighted MRI scans without using deformable registrations. We compare this method against two state-of-the-art methods within the voxel-based and atlas-based categories. Methods: The data consisted of CT and MRI scans of five cranial RT patients. To compare the performance of the different methods, a nested cross validation was done to find optimal model parameters for all the methods. Voxel-wise and geometric evaluations of the pCTs were done. Furthermore, a radiologic evaluation based on water equivalent path lengths was carried out, comparing the upper hemisphere of the head in the pCT and the real CT. Finally, the dosimetric accuracy was tested and compared for a photon treatment plan. Results: The pCTs produced with the patch-based method had the best voxel-wise, geometric, and radiologic agreement with the real CT, closely followed by the atlas-based method. In terms of the dosimetric accuracy, the patch-based method had average deviations of less than 0.5% in measures related to target coverage. Conclusions: We showed that a patch-based method could generate an accurate pCT based on conventional T{sub 1}-weighted MRI sequences and without deformable registrations. In our evaluations, the method performed better than existing voxel-based and atlas-based methods and showed a promising potential for RT of the brain based only on MRI.

  20. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    SciTech Connect (OSTI)

    Aslian, Hossein; Sadeghi, Mahdi; Mahdavi, Seied Rabie; Babapour Mofrad, Farshid; Astarakee, Mahdi; Khaledi, Navid; Fadavi, Pedram

    2013-09-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (SD) of 12.33 2.47 minutes, whereas it was 3.254 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 0.02, 2.05 0.66 cm, and 0.78 0.15 cm, and they were 0.82 0.03, 1.91 0.65 cm, and 0.7 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer.

  1. Planning Evaluation of C-Arm Cone Beam CT Angiography for Target Delineation in Stereotactic Radiation Surgery of Brain Arteriovenous Malformations

    SciTech Connect (OSTI)

    Kang, Jun; Huang, Judy; Gailloud, Philippe; Rigamonti, Daniele; Lim, Michael; Bernard, Vincent; Ehtiati, Tina; Ford, Eric C.

    2014-10-01

    Purpose: Stereotactic radiation surgery (SRS) is one of the therapeutic modalities currently available to treat cerebral arteriovenous malformations (AVM). Conventionally, magnetic resonance imaging (MRI) and MR angiography (MRA) and digital subtraction angiography (DSA) are used in combination to identify the target volume for SRS treatment. The purpose of this study was to evaluate the use of C-arm cone beam computed tomography (CBCT) in the treatment planning of SRS for cerebral AVMs. Methods and Materials: Sixteen consecutive patients treated for brain AVMs at our institution were included in this retrospective study. Prior to treatment, all patients underwent MRA, DSA, and C-arm CBCT. All images were coregistered using the GammaPlan planning system. AVM regions were delineated independently by 2 physicians using either C-arm CBCT or MRA, resulting in 2 volumes: a CBCT volume (VCBCT) and an MRA volume (V{sub MRA}). SRS plans were generated based on the delineated regions. Results: The average volume of treatment targets delineated using C-arm CBCT and MRA were similar, 6.40 cm{sup 3} and 6.98 cm{sup 3}, respectively (P=.82). However, significant regions of nonoverlap existed. On average, the overlap of the MRA with the C-arm CBCT was only 52.8% of the total volume. In most cases, radiation plans based on V{sub MRA} did not provide adequate dose to the region identified on C-arm CBCT; the mean minimum dose to V{sub CBCT} was 29.5%, whereas the intended goal was 45% (P<.001). The mean volume of normal brain receiving 12 Gy or more in C-arm CBCT-based plans was not greater than in the MRA-based plans. Conclusions: Use of C-arm CBCT images significantly alters the delineated regions of AVMs for SRS planning, compared to that of MRA/MRI images. CT-based planning can be accomplished without increasing the dose to normal brain and may represent a more accurate definition of the nidus, increasing the chances for successful obliteration.

  2. Clinical Value of [{sup 11}C]Methionine PET for Stereotactic Radiation Therapy With Intensity Modulated Radiation Therapy to Metastatic Brain Tumors

    SciTech Connect (OSTI)

    Miwa, Kazuhiro; Department of Clinical Brain Sciences, Gifu University Graduate School of Medicine, Minokamo, Gifu ; Matsuo, Masayuki; Shinoda, Jun; Aki, Tatsuki; Yonezawa, Shingo; Department of Clinical Brain Sciences, Gifu University Graduate School of Medicine, Minokamo, Gifu ; Ito, Takeshi; Asano, Yoshitaka; Department of Clinical Brain Sciences, Gifu University Graduate School of Medicine, Minokamo, Gifu ; Yamada, Mikito; Yokoyama, Kazutoshi; Yamada, Jitsuhiro; Yano, Hirohito; Iwama, Toru

    2012-12-01

    Purpose: This study investigated the clinical impact of {sup 11}C-labeled methionine-positron emission tomography (MET-PET) for stereotactic radiation therapy with intensity modulated radiation therapy (SRT-IMRT) in metastatic brain tumors. Methods and Materials: Forty-two metastatic brain tumors were examined. All tumors were treated with SRT-IMRT using a helical tomotherapy system. Gross tumor volume (GTV) was defined and drawn on the stereotactic magnetic resonance (MR) image, taking into account the respective contributions of MR imaging and MET-PET. Planning target volume (PTV) encompassed the GTV-PET plus a 2-mm margin. SRT-IMRT was performed, keeping the dose for PTV at 25-35 Gy in 5 fractions. The ratio of the mean value of MET uptake to the contralateral normal brain (L/N ratio) was plotted for the PTV prior to SRT-IMRT, at 3 months following SRT-IMRT, and at 6 months following SRT-IMRT. Tumor characteristic changes of MET uptake before and after SRT-IMRT were evaluated quantitatively, comparing them with MRI examination. Results: Mean {+-} SD L/N ratios were 1.95 {+-} 0.83, 1.18 {+-} 0.21, and 1.12 {+-} 0.25 in the pre-SRT-IMRT group, in the 3 months post-SRT-IMRT group, and in the 6 months post-SRT-IMRT group, respectively. Differences in the mean L/N ratio between the pre-SRT-IMRT group and the 3-month post-SRT-IMRT group and between the pre-SRT-IMRT group and the 6 month post-SRT-IMRT group were statistically significant, irrespective of MRI examination. Conclusions: We showed examples of metastatic lesions demonstrating significant decreases in MET uptake following SRT-IMRT. MET-PET seems to have a potential role in providing additional information, although MRI remains the gold standard for diagnosis and follow-up after SRT-IMRT. The present study is a preliminary approach, but to more clearly define the impact of PET-based radiosurgical assessment, further experimental and clinical analyses are required.

  3. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    SciTech Connect (OSTI)

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

    2014-01-10

    Highlights: Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. Mature BDNF plays an important role in the effects of forced exercise. Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male SpragueDawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNFpCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNFpCREB signaling in non-irradiation group. These results suggest that forced running exercise offers a potentially effective treatment for radiation-induced cognitive deficits.

  4. SU-E-T-570: Management of Radiation Oncology Patients with Cochlear Implant and Other Bionic Devices in the Brain and Head and Neck Regions

    SciTech Connect (OSTI)

    Guo, F.Q; Chen, Z; Nath, R

    2014-06-01

    Purpose: To investigate the current status of clinical usage of cochlear implant (CI) and other bionic devices (BD) in the brain and head and neck regions (BH and N) and their management in patients during radiotherapy to ensure patient health and safety as well as optimum radiation delivery. Methods: Literature review was performed with both CIs and radiotherapy and their variants as keywords in PubMed, INSPEC and other sources. The focus was on CIs during radiotherapy, but it also included other BDs in BHȦN, such as auditory brainstem implant, bionic retinal implant, and hearing aids, among others. Results: Interactions between CIs and radiation may cause CIs malfunction. The presence of CIs may also cause suboptimum dose distribution if a treatment plan was not well designed. A few studies were performed for the hearing functions of CIs under irradiations of 4 MV and 6 MV x-rays. However, x-rays with higher energies (10 to 18 MV) broadly used in radiotherapy have not been explored. These higher energetic beams are more damaging to electronics due to strong penetrating power and also due to neutrons generated in the treatment process. Modern CIs are designed with more and more complicated integrated circuits, which may be more susceptible to radiation damage and malfunction. Therefore, careful management is important for safety and treatment outcomes. Conclusion: Although AAPM TG-34, TG-63, and TG-203 (update of TG-34, not published yet) reports may be referenced for management of CIs and other BDs in the brain and H and N regions, a site- and device-specified guideline should be developed for CIs and other BDs. Additional evaluation of CI functions under clinically relevant set-ups should also be performed to provide clinicians with better knowledge in clinical decision making.

  5. Synchronization, non-linear dynamics and low-frequency fluctuations: Analogy between spontaneous brain activity and networked single-transistor chaotic oscillators

    SciTech Connect (OSTI)

    Minati, Ludovico E-mail: ludovico.minati@unitn.it

    2015-03-15

    In this paper, the topographical relationship between functional connectivity (intended as inter-regional synchronization), spectral and non-linear dynamical properties across cortical areas of the healthy human brain is considered. Based upon functional MRI acquisitions of spontaneous activity during wakeful idleness, node degree maps are determined by thresholding the temporal correlation coefficient among all voxel pairs. In addition, for individual voxel time-series, the relative amplitude of low-frequency fluctuations and the correlation dimension (D{sub 2}), determined with respect to Fourier amplitude and value distribution matched surrogate data, are measured. Across cortical areas, high node degree is associated with a shift towards lower frequency activity and, compared to surrogate data, clearer saturation to a lower correlation dimension, suggesting presence of non-linear structure. An attempt to recapitulate this relationship in a network of single-transistor oscillators is made, based on a diffusive ring (n = 90) with added long-distance links defining four extended hub regions. Similarly to the brain data, it is found that oscillators in the hub regions generate signals with larger low-frequency cycle amplitude fluctuations and clearer saturation to a lower correlation dimension compared to surrogates. The effect emerges more markedly close to criticality. The homology observed between the two systems despite profound differences in scale, coupling mechanism and dynamics appears noteworthy. These experimental results motivate further investigation into the heterogeneity of cortical non-linear dynamics in relation to connectivity and underline the ability for small networks of single-transistor oscillators to recreate collective phenomena arising in much more complex biological systems, potentially representing a future platform for modelling disease-related changes.

  6. SU-E-QI-03: Compartment Modeling of Dynamic Brain PET - The Effect of Scatter and Random Corrections On Parameter Errors

    SciTech Connect (OSTI)

    Häggström, I; Karlsson, M; Larsson, A; Schmidtlein, C

    2014-06-15

    Purpose: To investigate the effects of corrections for random and scattered coincidences on kinetic parameters in brain tumors, by using ten Monte Carlo (MC) simulated dynamic FLT-PET brain scans. Methods: The GATE MC software was used to simulate ten repetitions of a 1 hour dynamic FLT-PET scan of a voxelized head phantom. The phantom comprised six normal head tissues, plus inserted regions for blood and tumor tissue. Different time-activity-curves (TACs) for all eight tissue types were used in the simulation and were generated in Matlab using a 2-tissue model with preset parameter values (K1,k2,k3,k4,Va,Ki). The PET data was reconstructed into 28 frames by both ordered-subset expectation maximization (OSEM) and 3D filtered back-projection (3DFBP). Five image sets were reconstructed, all with normalization and different additional corrections C (A=attenuation, R=random, S=scatter): Trues (AC), trues+randoms (ARC), trues+scatters (ASC), total counts (ARSC) and total counts (AC). Corrections for randoms and scatters were based on real random and scatter sinograms that were back-projected, blurred and then forward projected and scaled to match the real counts. Weighted non-linearleast- squares fitting of TACs from the blood and tumor regions was used to obtain parameter estimates. Results: The bias was not significantly different for trues (AC), trues+randoms (ARC), trues+scatters (ASC) and total counts (ARSC) for either 3DFBP or OSEM (p<0.05). Total counts with only AC stood out however, with an up to 160% larger bias. In general, there was no difference in bias found between 3DFBP and OSEM, except in parameter Va and Ki. Conclusion: According to our results, the methodology of correcting the PET data for randoms and scatters performed well for the dynamic images where frames have much lower counts compared to static images. Generally, no bias was introduced by the corrections and their importance was emphasized since omitting them increased bias extensively.

  7. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    develops 3-D sensor array for detection of neural responses December 2, 2014 Neural degenerative diseases and traumatic injuries affect millions of people worldwide, motivating the development of neural prosthetic interfaces to restore sensory or motor function in affected individuals. Advances in neural sensing and stimulation interface technology would allow a more comprehensive understanding of neural function while leading to the development of hybrid biological-electronic sensor devices for

  8. Lawrence Livermore and IBM Collaborate to Build New Brain-Inspired Supercomputer: Chip-architecture breakthrough accelerates path to exascale computing; helps computers tackle complex, cognitive tasks such as pattern recognition sensory processing

    Broader source: Energy.gov [DOE]

    Lawrence Livermore National Laboratory (LLNL) today announced it will receive a first-of-a-kind brain-inspired supercomputing platform for deep learning developed by IBM Research. Based on a breakthrough neurosynaptic computer chip called IBM TrueNorth, the scalable platform will process the equivalent of 16 million neurons and 4 billion synapses and consume the energy equivalent of a hearing aid battery – a mere 2.5 watts of power.

  9. Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

    SciTech Connect (OSTI)

    Leavens, C; Wronski, M; Lee, YK; Ruschin, M; Soliman, H; Sahgal, A

    2014-08-15

    Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter and arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.

  10. Type B Accident Investigation Board Report Grout Injection Operator...

    Energy Savers [EERE]

    and no damage to any structures inside the calvareum (i.e., no evidence of brain injury). Page 16 2.4. Investigation Readiness and Accident Scene Preservation The...

  11. The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

    SciTech Connect (OSTI)

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E.; Damilakis, John

    2013-01-15

    Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio mainly to the peripheral region of the phantom. Conclusions: Despite typical peak doses to skin, eye lens, brain, and RBM from the standard low-dose brain perfusion 256-slice CT protocol are well below the corresponding thresholds for the induction of erythema, cataract, cerebrovascular disease, and depression of hematopoiesis, respectively, every effort should be made toward optimization of the procedure and minimization of dose received by these tissues. The current study provides evidence that the use of the narrower bowtie filter available may considerably reduce peak absorbed dose to all above radiosensitive tissues with minimal deterioration in image quality. Considerable reduction in peak eye-lens dose may also be achieved by positioning patient head center a few centimeters above isocenter during the exposure.

  12. Positron Scanner for Brain Tumors

    DOE R&D Accomplishments [OSTI]

    Robertson, J. S.; Bozzo, S. R.

    1964-10-09

    It was thought that if a multi-detector device could be developed, the scanning time would be greatly shortened, with such consequent advantages as being able to work with lower dose of radiation, to obtain serial determinations, and to work with shorter-lived isotopes.

  13. SU-C-18A-05: Registration Accuracy of MR-Based Images to On-Board Megavoltage Cone-Beam CT for Brain Patient Setup

    SciTech Connect (OSTI)

    Pinnaduwage, D S; Chen, J; Descovich, M; Pouliot, J; Hwang, Ken-Ping

    2014-06-01

    Purpose: To quantify the difference in isocenter shifts when co-registering MR and MR-based pseudo CTs (pCT) with on-board megavoltage conebeam CT (CBCT) images. Methods: Fast Spoiled Gradient Echo MRs were used to generate pCTs (research version of Advantage Sim MD, GE Healthcare) for ten patients who had prior brain radiotherapy. The planning CT (rCT) for each was co-registered with the MR, and the plan isocenter and two other reference points were transferred to the MR and pCT. CBCT images (with the machine isocenter) from a single treatment day were coregistered with the 3 test images (MR, pCT and rCT), by two observers and by an automated registration algorithm. The reference points were used to calculate patient shifts and rotations from the registrations. The shifts calculated from the test image registrations were compared to each other and to the shifts performed by the therapists who treated the patients on that day. Results: The average difference in absolute value between the isocenter shifts from the MR-, pCT- and rCT-CBCT registrations, and the therapist shifts, were 2.02, 3.01 and 0.89 mm (craniocaudal), 1.14, 1.34 and 0.46 mm (lateral), and 1.37, 3.43 and 1.43 mm (vertical), respectively. The MR- and pCT-CBCT registrations differed by 1.99, and 2.53 mm (craniocaudal), 1.36, and 1.37 mm (lateral), and 0.74 and 2.34 mm (vertical), respectively, from the average rCT-CBCT shifts. On average, differences of 2.39 (craniocaudal), 1.28 (lateral) and 2.84 mm (vertical) were seen between the MR and pCT shifts. Rotations relative to the CBCT coordinate system were on average <2 for the MR and rCT, and <6 for the pCT. Conclusion: In this study, FSPGR MR-CBCT registrations were more precise compared to the pCT-CBCT registrations. For improved accuracy, MR sequences that are optimal for bony anatomy visualization are necessary. GE healthcare has provided a research version of Advantage Sim MD to UCSF. No financial support was provided.

  14. Fall Protection Can Prevent Serious Injuries

    Broader source: Energy.gov (indexed) [DOE]

    protection requirements were not followed. According to the Occupational Safety and Health Administration (OSHA), falls from elevations, including into holes in floors, are the...

  15. Fall Protection Can Prevent Serious Injuries

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    an operations technician was observed working from an elevated scissor lift while standing on its mid-rails. He was wearing a full- body harness with shock-absorbing lanyard,...

  16. SU-E-J-39: Comparison of PTV Margins Determined by In-Room Stereoscopic Image Guidance and by On-Board Cone Beam Computed Tomography Technique for Brain Radiotherapy Patients

    SciTech Connect (OSTI)

    Ganesh, T; Paul, S; Munshi, A; Sarkar, B; Krishnankutty, S; Sathya, J; George, S; Jassal, K; Roy, S; Mohanti, B

    2014-06-01

    Purpose: Stereoscopic in room kV image guidance is a faster tool in daily monitoring of patient positioning. Our centre, for the first time in the world, has integrated such a solution from BrainLAB (ExacTrac) with Elekta's volumetric cone beam computed tomography (XVI). Using van Herk's formula, we compared the planning target volume (PTV) margins calculated by both these systems for patients treated with brain radiotherapy. Methods: For a total of 24 patients who received partial or whole brain radiotherapy, verification images were acquired for 524 treatment sessions by XVI and for 334 sessions by ExacTrac out of the total 547 sessions. Systematic and random errors were calculated in cranio-caudal, lateral and antero-posterior directions for both techniques. PTV margins were then determined using van Herk formula. Results: In the cranio-caudal direction, systematic error, random error and the calculated PTV margin were found to be 0.13 cm, 0.12 cm and 0.41 cm with XVI and 0.14 cm, 0.13 cm and 0.44 cm with ExacTrac. The corresponding values in lateral direction were 0.13 cm 0.1 cm and 0.4 cm with XVI and 0.13 cm, 0.12 cm and 0.42 cm with ExacTrac imaging. The same parameters for antero-posterior were for 0.1 cm, 0.11 cm and 0.34 cm with XVI and 0.13 cm, 0.16 cm and 0.43 cm with ExacTrac imaging. The margins estimated with the two imaging modalities were comparable within ± 1 mm limit. Conclusion: Verification of setup errors in the major axes by two independent imaging systems showed the results are comparable and within ± 1 mm. This implies that planar imaging based ExacTrac can yield equal accuracy in setup error determination as the time consuming volumetric imaging which is considered as the gold standard. Accordingly PTV margins estimated by this faster imaging technique can be confidently used in clinical setup.

  17. SU-E-J-70: Feasibility Study of Dynamic Arc and IMRT Treatment Plans Utilizing Vero Treatment Unit and IPlan Planning Computer for SRS/FSRT Brain Cancer Patients

    SciTech Connect (OSTI)

    Huh, S; Lee, S; Dagan, R; Malyapa, R; Mendenhall, N; Mendenhall, W; Ho, M; Hough, D; Yam, M; Li, Z

    2014-06-01

    Purpose: To investigate the feasibility of utilizing Dynamic Arc (DA) and IMRT with 5mm MLC leaf of VERO treatment unit for SRS/FSRT brain cancer patients with non-invasive stereotactic treatments. The DA and IMRT plans using the VERO unit (BrainLab Inc, USA) are compared with cone-based planning and proton plans to evaluate their dosimetric advantages. Methods: The Vero treatment has unique features like no rotational or translational movements of the table during treatments, Dynamic Arc/IMRT, tracking of IR markers, limitation of Ring rotation. Accuracies of the image fusions using CBCT, orthogonal x-rays, and CT are evaluated less than ∼ 0.7mm with a custom-made target phantom with 18 hidden targets. 1mm margin is given to GTV to determine PTV for planning constraints considering all the uncertainties of planning computer and mechanical uncertainties of the treatment unit. Also, double-scattering proton plans with 6F to 9F beams and typical clinical parameters, multiple isocenter plans with 6 to 21 isocenters, and DA/IMRT plans are evaluated to investigate the dosimetric advantages of the DA/IMRT for complex shape of targets. Results: 3 Groups of the patients are divided: (1) Group A (complex target shape), CI's are same for IMRT, and DGI of the proton plan are better by 9.5% than that of the IMRT, (2) Group B, CI of the DA plans (1.91+/−0.4) are better than cone-based plan, while DGI of the DA plan is 4.60+/−1.1 is better than cone-based plan (5.32+/−1.4), (3) Group C (small spherical targets), CI of the DA and cone-based plans are almost the same. Conclusion: For small spherical targets, cone-based plans are superior to other 2 plans: DS proton and DA plans. For complex or irregular plans, dynamic and IMRT plans are comparable to cone-based and proton plans for complex targets.

  18. MO-G-17A-07: Improved Image Quality in Brain F-18 FDG PET Using Penalized-Likelihood Image Reconstruction Via a Generalized Preconditioned Alternating Projection Algorithm: The First Patient Results

    SciTech Connect (OSTI)

    Schmidtlein, CR; Beattie, B; Humm, J; Li, S; Wu, Z; Xu, Y; Zhang, J; Shen, L; Vogelsang, L; Feiglin, D; Krol, A

    2014-06-15

    Purpose: To investigate the performance of a new penalized-likelihood PET image reconstruction algorithm using the 1{sub 1}-norm total-variation (TV) sum of the 1st through 4th-order gradients as the penalty. Simulated and brain patient data sets were analyzed. Methods: This work represents an extension of the preconditioned alternating projection algorithm (PAPA) for emission-computed tomography. In this new generalized algorithm (GPAPA), the penalty term is expanded to allow multiple components, in this case the sum of the 1st to 4th order gradients, to reduce artificial piece-wise constant regions (“staircase” artifacts typical for TV) seen in PAPA images penalized with only the 1st order gradient. Simulated data were used to test for “staircase” artifacts and to optimize the penalty hyper-parameter in the root-mean-squared error (RMSE) sense. Patient FDG brain scans were acquired on a GE D690 PET/CT (370 MBq at 1-hour post-injection for 10 minutes) in time-of-flight mode and in all cases were reconstructed using resolution recovery projectors. GPAPA images were compared PAPA and RMSE-optimally filtered OSEM (fully converged) in simulations and to clinical OSEM reconstructions (3 iterations, 32 subsets) with 2.6 mm XYGaussian and standard 3-point axial smoothing post-filters. Results: The results from the simulated data show a significant reduction in the 'staircase' artifact for GPAPA compared to PAPA and lower RMSE (up to 35%) compared to optimally filtered OSEM. A simple power-law relationship between the RMSE-optimal hyper-parameters and the noise equivalent counts (NEC) per voxel is revealed. Qualitatively, the patient images appear much sharper and with less noise than standard clinical images. The convergence rate is similar to OSEM. Conclusions: GPAPA reconstructions using the 1{sub 1}-norm total-variation sum of the 1st through 4th-order gradients as the penalty show great promise for the improvement of image quality over that currently achieved with clinical OSEM reconstructions.

  19. Brain Receptor Structures Key to Future Therapeutics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; and NMDA, N-methyl-D-aspartate. The receptors used in the studies-from the Norwegian rat and the frog Xenopus...

  20. A Designed Protein Maps Brain Activity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    are connected and how the engineered mutations in each allow the combined proteins to function together as one unit. Crystal structure of calcium-free CaMPARI. Three orthogonal...

  1. "Artificial" brains, electrical grids, and disease modeling:...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Deputy Principal Associate Director Duncan McBranch will discuss LDRD impacts on border security and the nation's energy grid at 1 p.m. The event is an ideal opportunity...

  2. AEP Climate Change Strategy Bruce Braine

    U.S. Energy Information Administration (EIA) Indexed Site

    (e.g., IGCC, Ultra- supercritical PC and CCS) AEP must be a leader in addressing climate ... Widely Deployed After 2020 None CCS 64 GWe by 2030 12.5 GWe by 2030 Nuclear Generation 70 ...

  3. Scientists examine proton radiography of brain mockup

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the NNSA. Additional researchers include Fesseha Mariam of Subatomic Physics, Kurt Schoenberg of Experimental Physical Sciences, Cris Barnes of Physics Division and German...

  4. Human Brain vs. Computer | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computer Processors Beat the Human Mind in the Future? Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new ...

  5. Occupational Injury & Illness System (01&15) PIA, Idaho National...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Employees' Occupational Illness Compensation Program Act (EEOICPA) Tracking Database, INL Energy Employees' Occupational Illness Compensation Program Occupational Medicine - ...

  6. Future directions in therapy of whole body radiation injury

    SciTech Connect (OSTI)

    Cronkite, E.P.

    1989-01-01

    Clinicians have long known that marked granulocytopenia predisposed patients to bacterial infections either from pathogens or commensal organisms with which an individual usually lives in harmony. Evidence that infection was of major importance derives from several observations: (a) clinical observations of bacterial infection in human beings exposed to atomic bomb radiation in Hiroshima and Nagasaki, in reactor accidents, and in large animals dying from radiation exposure, (b) correlative studies on mortality rate, time of death, and incidence of positive culture in animals, (c) challenge of irradiated animals with normally non-virulent organisms, (d) studies of germ free mice and rats, and (e) studies of the effectiveness of antibiotics in reducing mortality rate. General knowledge and sound experimental data on animals and man clearly demonstrated that the sequelae of pancytopenia (bacterial infection, thrombopenic hemorrhage, and anemia) are the lethal factors. A lot of research was required to demonstrate that there were no mysterious radiations toxins, that hyperheparinemia was not a cause of radiation hemorrhage and that radiation hemorrhage could be prevented by fresh platelet transfusions.

  7. ORISE: Illness and Injury Surveillance, Radiation Exposure, and...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    fulfill agency requests for customized data, or support the routine review of health assessment programs. A list of ORISE reports focused on occupational exposure and worker...

  8. RL-2007OccupationalInjuryIllness(OII)PIA.pdf

    Energy Savers [EERE]

  9. Occupational Injury & Illness System (01&15) PIA, Idaho National...

    Energy Savers [EERE]

    Tracking Database, INL Energy Employees' Occupational Illness Compensation Program Occupational Medicine - Assistant PIA, Idaho National Laboratory VisitDosimBadgeTrckg-PIA.pdf...

  10. ORISE: Worker Health Studies - Illness and Injury Surveillance

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    based on continuous collection, analysis and interpretation of selected morbidity, demographic and occupational exposure data. ORISE serves as the data center for IISP and in...

  11. ORISE: DOE Illness and Injury Surveillance Program 10-Year Summary...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    sites' workforce health. Reports enable trends assessment by worker group, age group, gender and health event. ORISE conducts follow-ups with SOMDs regarding health events...

  12. Operating Experience Level 3, Fall Protection Can Prevent Serious Injuries

    Broader source: Energy.gov [DOE]

    2015-05: This Operating Experience Level 3 (OE-3) document provides information about a safety concern related to incidents at Department of Energy (DOE) facilities in which fall protection requirements were not followed. According to the Occupational Safety and Health Administration (OSHA), falls from elevations, including into holes in floors, are the leading cause of worker fatalities in the U.S. construction industry.

  13. Celiac Injury Due to Arcuate Ligament: An Endovascular Approach

    SciTech Connect (OSTI)

    Zini, Chiara Corona, Mario Boatta, Emanuele Wlderk, Andrea Salvatori, Filippo Maria Fanelli, Fabrizio

    2013-06-15

    Celiac trunk injures are rare events, with high mortality rates and difficult management. Endovascular treatment may be considered to avoid bleeding. We report a case of severe bleeding in a 37-year-old man resulting from celiac trunk stretching after a motorcycle crash. Because direct celiac trunk catheterization was not possible, a retrograde catheterization of the common hepatic artery was performed via the superior mesenteric artery. Two vascular plugs (type IV) were released, and the exclusion of the celiac trunk origin was completed with the deployment of an aortic cuff. The patient's clinical condition immediately improved, and after 6 months' follow-up, imaging confirmed the complete exclusion of the celiac trunk.

  14. Blockage of mitochondrial calcium uniporter prevents iron accumulation in a model of experimental subarachnoid hemorrhage

    SciTech Connect (OSTI)

    Yan, Huiying; Hao, Shuangying; Sun, Xiaoyan; Zhang, Dingding; Gao, Xin; Yu, Zhuang; Li, Kuanyu; Hang, Chun-Hua

    2015-01-24

    Highlights: • Iron accumulation was involved in the acute phase following SAH. • Blockage of MCU could attenuate cellular iron accumulation following SAH. • Blockage of MCU could decrease ROS generation and improve cell energy supply following SAH. • Blockage of MCU could alleviate apoptosis and brain injury following SAH. - Abstract: Previous studies have shown that iron accumulation is involved in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH) and chelation of iron reduced mortality and oxidative DNA damage. We previously reported that blockage of mitochondrial calcium uniporter (MCU) provided benefit in the early brain injury after experimental SAH. This study was undertaken to identify whether blockage of MCU could ameliorate iron accumulation-associated brain injury following SAH. Therefore, we used two reagents ruthenium red (RR) and spermine (Sper) to inhibit MCU. Sprague–Dawley (SD) rats were randomly divided into four groups including sham, SAH, SAH + RR, and SAH + Sper. Biochemical analysis and histological assays were performed. The results confirmed the iron accumulation in temporal lobe after SAH. Interestingly, blockage of MCU dramatically reduced the iron accumulation in this area. The mechanism was revealed that inhibition of MCU reversed the down-regulation of iron regulatory protein (IRP) 1/2 and increase of ferritin. Iron–sulfur cluster dependent-aconitase activity was partially conserved when MCU was blocked. In consistence with this and previous report, ROS levels were notably reduced and ATP supply was rescued; levels of cleaved caspase-3 dropped; and integrity of neurons in temporal lobe was protected. Taken together, our results indicated that blockage of MCU could alleviate iron accumulation and the associated injury following SAH. These findings suggest that the alteration of calcium and iron homeostasis be coupled and MCU be considered to be a therapeutic target for patients suffering from SAH.

  15. Hyperspectral microscope for in vivo imaging of microstructures and cells in tissues

    DOE Patents [OSTI]

    Demos; Stavros G.

    2011-05-17

    An optical hyperspectral/multimodal imaging method and apparatus is utilized to provide high signal sensitivity for implementation of various optical imaging approaches. Such a system utilizes long working distance microscope objectives so as to enable off-axis illumination of predetermined tissue thereby allowing for excitation at any optical wavelength, simplifies design, reduces required optical elements, significantly reduces spectral noise from the optical elements and allows for fast image acquisition enabling high quality imaging in-vivo. Such a technology provides a means of detecting disease at the single cell level such as cancer, precancer, ischemic, traumatic or other type of injury, infection, or other diseases or conditions causing alterations in cells and tissue micro structures.

  16. High School Students Gear Up for Battle of the Brains

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Feb. 17, 1999 — What is the maximum distance an electron can travel in a nanosecond? Which planet has a moon almost as big as the planet itself? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) 1999 Denver Regional Science Bowl Feb. 27 at the Colorado School of Mines in Golden. More than 20 student teams from rural communities to metropolitan areas across the state will compete in this rapid-fire

  17. High School Students Gear Up for Battle of the Brains

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Jan. 31, 2000 - Which planet in the solar system has a day that lasts longer than its year? If 64 sugar cubes were glued into one solid cube and spray-painted red, how many of the original cubes would have exactly two red surfaces? High school students from across Colorado will face such questions as they test their mental agility in the U.S. Department of Energy's (DOE) Colorado Science Bowl on Feb. 12 at the Colorado School of Mines in Golden. More than 25 student teams from rural communities

  18. Neural Interface for Deep Brain Stimulation (Conference) | SciTech...

    Office of Scientific and Technical Information (OSTI)

    Number(s): LLNL-CONF-638803 DOE Contract Number: W-7405-ENG-48 Resource Type: Conference Resource Relation: Conference: Presented at: IEEE Neural Engineering, San Diego, CA, United...

  19. Chronic, Multi-Contact, Neural Interface for Deep Brain Stimulation...

    Office of Scientific and Technical Information (OSTI)

    DOE Contract Number: W-7405-ENG-48 Resource Type: Conference Resource Relation: Conference: Presented at: IEEE Conference on Neural Engineering, San Diego, CA, United...

  20. Neural Interface for Deep Brain Stimulation (Conference) | SciTech...

    Office of Scientific and Technical Information (OSTI)

    Report Number(s): LLNL-CONF-638803 DOE Contract Number: W-7405-ENG-48 Resource Type: Conference Resource Relation: Conference: Presented at: IEEE Neural Engineering, San Diego, CA, ...

  1. Chronic, Multi-Contact, Neural Interface for Deep Brain Stimulation...

    Office of Scientific and Technical Information (OSTI)

    Report Number(s): LLNL-CONF-644462 DOE Contract Number: W-7405-ENG-48 Resource Type: Conference Resource Relation: Conference: Presented at: IEEE Conference on Neural Engineering, ...

  2. Inhibition of brain tumor cell proliferation by alternating electric fields

    SciTech Connect (OSTI)

    Jeong, Hyesun; Oh, Seung-ick; Hong, Sunghoi E-mail: radioyoon@korea.ac.kr; Sung, Jiwon; Jeong, Seonghoon; Yoon, Myonggeun E-mail: radioyoon@korea.ac.kr; Koh, Eui Kwan

    2014-11-17

    This study was designed to investigate the mechanism by which electric fields affect cell function, and to determine the optimal conditions for electric field inhibition of cancer cell proliferation. Low-intensity (<2 V/cm) and intermediate-frequency (100–300 kHz) alternating electric fields were applied to glioblastoma cell lines. These electric fields inhibited cell proliferation by inducing cell cycle arrest and abnormal mitosis due to the malformation of microtubules. These effects were significantly dependent on the intensity and frequency of applied electric fields.

  3. Unexpected Type of Failure of Thermal Battery Resulting in a Near Miss to a Serious Injury

    SciTech Connect (OSTI)

    Richter, Daena Kei

    2015-10-01

    On 6/26/2015 at 1445 in 894/136, a thermal battery (approximately the size of a commercial size C cell) experienced an unexpected failure following a routine test where the battery is activated. The failure occurred while a test operator was transferring the battery from the testing primary containment box to another containment box within the same room; initial indications are that the battery package ruptured after it went into thermal runaway which led to the operator receiving bruising to the palm of the hand from the pressure of the expulsion. The operator was wearing the prescribed PPE, which was safety glasses and a high temperature glove on the hand that was holding the battery.

  4. Research Recruiting Endogenous Tissue Stem Cells to Repair Injury and Degeneration

    SciTech Connect (OSTI)

    Peterson, Daniel A.

    2014-10-22

    This report lists bibliographic information about meeting papers and journal articles resulting from this work, and basic information on new grant applications that this work was used to support.

  5. Mitigation and Treatment of Radiation-Induced Thoracic Injury With a Cyclooxygenase-2 Inhibitor, Celecoxib

    SciTech Connect (OSTI)

    Hunter, Nancy R.; Valdecanas, David [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao Zhongxing [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Milas, Luka [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Thames, Howard D. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mason, Kathy A., E-mail: kmason@mdanderson.org [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-02-01

    Purpose: To test whether a cyclooxygenase-2 inhibitor (celecoxib) could reduce mortality resulting from radiation-induced pneumonitis. Methods and Materials: Celecoxib was given to mice twice daily for 40 consecutive days starting on the day of local thoracic irradiation (LTI) or 40 or 80 days later. C3Hf/KamLaw mice were observed for morbidity, and time to death was determined. Results were analyzed using the Cox proportional hazards model. Results: Timing of celecoxib relative to LTI determined efficacy. A significant reduction in time to death was achieved only when celecoxib was started 80 days after LTI, corresponding to the time when pneumonitis is expressed. For these mice the reduction in mortality was quantified as a hazard ratio for mortality of treated vs untreated of 0.36 (95% confidence interval [CI] 0.24-0.53), thus significantly less than 1.0. Correspondingly, the median lethal dose for treated mice (12.9 Gy; 95% CI 12.55-13.25 Gy) was significantly (P=.026) higher than for untreated mice (12.4 Gy; 95% CI 12.2-12.65 Gy). Conclusions: Celecoxib significantly reduced lung toxicity when administered months after LTI when the deleterious effects of radiation were expressed. The schedule-dependent reduction in fatal pneumonitis suggests that celecoxib could be clinically useful by reintroduction of treatment months after completion of radiation therapy. These findings may be important for designing clinical trials using cyclooxygenase-2 inhibitors to treat radiation-induced lung toxicity as a complement to concurrent radiation therapy of lung cancers.

  6. EM Occupational Injury and Illness Rates Continued to Decline in Fiscal Year 2011

    Broader source: Energy.gov [DOE]

    WASHINGTON, D.C. – The EM Office of Safety and Security Program conducts analysis of EM-wide safety performance on a quarterly basis to provide senior management a tool to compare and evaluate performance and identify emergent trends and make performance comparisons between sites and contractors of varying size and risk.

  7. Foreign offshore worker injuries in foreign waters: why a United States forum

    SciTech Connect (OSTI)

    Sutterfield, J.R.

    1981-07-01

    When foreigners are injured or killed in offshore oil operations in foreign jurisdictional waters, US laws do not always apply as they would if the plaintiffs are American or resident aliens. The courts must first consider whether the Jones Act, Death on the High Seas Act, general maritime law, or a combination of laws applies and whether the court should assume jurisdiction or use the doctrine of forum non conveniens. Cases involving foreign offshore workers are used to illustrate the factors involved in each application and to consider the foreign-policy implication when foreign nationals assume that American laws and morality accompany multinational business. Congress has yet to resolve the issues, although a bill was proposed in 1980. 75 references. (DCK)

  8. DIRECT COSTS OF DISABLING WORKPLACE INJURIES GROW 2.5 PERCENT

    Broader source: Energy.gov [DOE]

    April 7, 2003 Annual Liberty Mutual Workplace Safety Index Shows Direct Costs of the Three Leading Causes of Workplace Incidents Grew Significantly Faster...

  9. U.S. Department of Energy Illness and Injury Surveillance Program...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    their absence rates for diseases such as diabetes and hypertension are increasing as well. ......... 34 Diabetes ......

  10. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    SciTech Connect (OSTI)

    Xu, Jiajun; Yang, Ming; Kosterin, Paul; Salzberg, Brian M.; Milovanova, Tatyana N.; Bhopale, Veena M.; Thom, Stephen R.

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in nave mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. MPs are lysed by infusing the surfactant polyethylene glycol telomere B. CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  11. Breaking a Cycle-Free Lifestyle for Earth Day

    Broader source: Energy.gov [DOE]

    One woman works through traumatic bicycle-related experiences while contemplating the purchase of a new bike for Earth Day.

  12. A Spectrum of Nerve Injury after Thermal Ablation: A Report of Four Cases and Review of the Literature

    SciTech Connect (OSTI)

    Philip, Asher; Gupta, Sanjay Ahrar, Kamran Tam, Alda L.

    2013-10-15

    Thermal ablation is an accepted alternative for the palliation of pain from bone metastases. Although rare, neurologic complications after thermal ablation have been reported. We present four cases, including two cases of rapid reversal of postcryoablation neurapraxia after the administration of steroid therapy, and review the literature.

  13. Type B Accident Investigation of the January 28, 2003, Fall and Injury at the Stanford Linear Accelerator Center

    Broader source: Energy.gov [DOE]

    This report is an independent product of the Type B Accident Investigation Board appointed by John S. Muhlestein, Director, Stanford Site Office (DOE/SC), U.S. Department of Energy.

  14. Operation Greenhouse. Scientific Director's report of atomic-weapon tests at Eniwetok, 1951. Annex 2. 7. Thermal radiation injury

    SciTech Connect (OSTI)

    Pearse, H.E.; Kingsley, H.D.; Schilling, J.A.; Hogg; Blakney, R.M.

    1985-09-01

    Information concerning the flash burn resulting from an atomic bomb explosion was necessary to understand the lesion, its systematic effects, and prevention and treatment of these effects. In order to reproduce similar sources in the laboratory, it was essential to know the characteristics of the energy producing the biological effect. In order to obtain this information, anesthetized experimental animals were placed in shielded positions at varying distances from bomb zero to cover a wide range of thermal-radiation intensities. Small areas of each animal's skin were exposed through aperture plates which were designed to analyze burn production as a function of time, intensity, and spectrum. Protection of the animal by fabrics covering the skin was also evaluated. Following exposure, animals were retrieved from the exposure stations and transported to a laboratory for analysis of the burn lesions by description, color photography, and microscopic study of biopsy materials.

  15. A Close Cut: A Technical Report of Endovascular Removal of a Penetrating Intravascular Foreign Body after a Lawn Mowing Injury

    SciTech Connect (OSTI)

    Tapping, C. R.; Gallo, A.; Silva, R. J. De; Uberoi, R.

    2012-12-15

    We present a case of endovascular retrieval of a penetrating foreign body that was originally lodged in the mediastinum and then migrated to the hepatic vein. The steel nail entered the thorax and traversed the left lung causing a pneumothorax. The patient underwent a thoracotomy, but the foreign body had migrated from its original mediastinal position. A postsurgical CT showed that the object was below the right hemidiaphragm. Diagnostic venogram demonstrated that the object was in the main hepatic vein. Using a double-snare technique, the object was safely and successfully removed from the hepatic vein via the right common femoral vein.

  16. La Vida Robot - High School Engineering Program Combats Engineering Brain Drain

    ScienceCinema (OSTI)

    Cameron, Allan; Fredi, Lajvardi

    2009-09-01

    Carl Hayden High School has built an impressive reputation with its robotics club. At a time when interest in science, math and engineering is declining, the Falcon Robotics club has young people fired up about engineering. Their program in underwater robots (MATE) and FIRST robotics is becoming a national model, not for building robots, but for building engineers. Teachers Fredi Lajvardi and Allan Cameron will present their story (How kids 'from the mean streets of Phoenix took on the best from M.I.T. in the national underwater bot championship' - Wired Magazine, April 2005) and how every student needs the opportunity to 'do real engineering.'

  17. Unlocking the brain's mysteries: Meet the bioengineers behind next-generation neural devices

    ScienceCinema (OSTI)

    Pannu, Sat; Shah, Kedar; Tolosa, Vanessa; Tooker, Angela

    2015-02-20

    Bioengineers in the Neural Technologies Group at Lawrence Livermore are creating the next generation of clinical- and research-quality neural interfaces. The goal is to gain a fundamental understanding of neuroscience, treat a variety of debilitating neurological disorders (such as Parkinson's, depression, and epilepsy), and restore lost neural functions such as sight, hearing, and mobility.

  18. A Phase I Study of Short-Course Accelerated Whole Brain Radiation...

    Office of Scientific and Technical Information (OSTI)

    Cattolica del S. Cuore, Campobasso (Italy) Department of Radiation Oncology, The Lacks Cancer Center Saint Mary's Health Care, Grand Rapids, Michigan (United States) Department of...

  19. Brains, Knees, . . . and now Batteries | U.S. DOE Office of Science...

    Office of Science (SC) Website

    As part of the Northeastern Center for Chemical Energy Storage EFRC, a research team from New York University, Stony Brook University, and Cambridge University has developed a ...

  20. Unlocking the brain's mysteries: Meet the bioengineers behind next-generation neural devices

    SciTech Connect (OSTI)

    Pannu, Sat; Shah, Kedar; Tolosa, Vanessa; Tooker, Angela

    2014-10-02

    Bioengineers in the Neural Technologies Group at Lawrence Livermore are creating the next generation of clinical- and research-quality neural interfaces. The goal is to gain a fundamental understanding of neuroscience, treat a variety of debilitating neurological disorders (such as Parkinson's, depression, and epilepsy), and restore lost neural functions such as sight, hearing, and mobility.

  1. In-vivo measurement of lithium in the brain and other organs

    DOE Patents [OSTI]

    Vartsky, D.; Wielopolski, L.; LoMonte, A.F.; Ellis, K.J.; Cohn, S.H.

    1983-08-26

    An in-vivo method of measurement of the amount of lithium present in tissue and organs of breathing animals is described. The basis for the technique is the lithium-1 neutron interaction - /sup 6/Li(n,..cap alpha..)T. The lithium is irradiated with thermal neutrons to produce tritium atoms. The tritium diffuses into the tissues and is exhaled. By measuring the amount of tritium exhaled, the lithium concentration in the irradiated zone is determined.

  2. Security Cases | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    a Local Security Office (LSO) cited a DOE psychiatrist's diagnoses of Post-Traumatic Stress Disorder and Delusional Disorder. The Administrative Judge found that the individual...

  3. Gelatin based on Power-gel.TM. as solders for Cr.sup.4+laser tissue welding and sealing of lung air leak and fistulas in organs

    DOE Patents [OSTI]

    Alfano, Robert R.; Tang, Jing; Evans, Jonathan M.; Ho, Peng Pei

    2006-04-25

    Laser tissue welding can be achieved using tunable Cr.sup.4+ lasers, semiconductor lasers and fiber lasers, where the weld strength follows the absorption spectrum of water. The use of gelatin and esterified gelatin as solders in conjunction with laser inducted tissue welding impart much stronger tensile and torque strengths than albumin solders. Selected NIR wavelength from the above lasers can improve welding and avoid thermal injury to tissue when used alone or with gelatin and esterified gelatin solders. These discoveries can be used to enhance laser tissue welding of tissues such as skin, mucous, bone, blood vessel, nerve, brain, liver, pancreas, spleen, kidney, lung, bronchus, respiratory track, urinary tract, gastrointestinal tract, or gynecologic tract and as a sealant for pulmonary air leaks and fistulas such as intestinal, rectal and urinary fistulas.

  4. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    SciTech Connect (OSTI)

    Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young

    2011-06-17

    Highlights: {yields} Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. {yields} Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  5. Microsoft PowerPoint - 1_Pete_Deessaules_Brain_Horn_NMMSS_2014_screensaver.ppt [Compatibility Mode]

    National Nuclear Security Administration (NNSA)

    Welcome Pete Dessaules, NNSA Brian Horn, NRC

  6. Type B Accident Investigation Board Report on the July 25, 1997, Contract Brush Cutter Injury on the Ashe-Marion #2 500 kV Line

    Broader source: Energy.gov [DOE]

    On July 25, 1997, at 1205 hours, a contract hand brush cutter was seriously injured when he felled a tree close to a Bonneville Power Administration energized transmission power line, located within a BPA transmission-line corridor.

  7. Type B Accident Investigation Board Report on the May 7, 1997, Worker Injury at the Hanford Site Canister Storage Building Construction Site, Richland, Washington

    Broader source: Energy.gov [DOE]

    This report is an independent product of the Type B Accident Investigation Board appointed by Michael S. Cowan, Chief Program Officer, Western Area Power Administration.

  8. Type B Accident Investigation of the Serious Personal Injury while Doble Testing at the Western Area Power Administration Hayden Substation, May 19, 1999

    Broader source: Energy.gov [DOE]

    On May 19, 1999, at 10:31 a.m., four Western Area Power Administration (Western) employees were performing Doble testing on a circuit breaker at Hayden Substation in Routt County, Colorado. Three electricians were injured when the high-voltage lead (HVL) of the Doble test set encroached on the minimum approach distance to an energized part outside clearance boundaries, drawing arcing faults.

  9. Type B Accident Investigation Board Report on the November 1, 1999, Construction Injury at the Monticello Mill Tailings Remedial Action Site, Monticello, Utah

    Broader source: Energy.gov [DOE]

    This report is an independent product of the Type B accident investigation board appointed by R. E. Glass, Manager, Albuquerque Operations Office.

  10. Type B Accident Investigation Of The February 25, 2009 Injury To A Passenger In An Electric Cart At The Waste Isolation Pilot Plant, Carlsbad, New Mexico

    Broader source: Energy.gov [DOE]

    This report is a product of an Accident Investigation Board appointed by David C. Moody, Manager, Carlsbad Field Office, Department of Energy, on March 4, 2009.

  11. Microsoft Word - InjIllRptGuide2011rev8162012.docx

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Injury and Illness Reporting Guide August 2012 Office of Corporate Analysis Office of Health, Safety and Security i TABLE OF CONTENTS Introduction ..................................................................................................................................... 1 Injury and Illness Reporting Using CAIRS .................................................................................... 2 Data Elements: Injury and Illness Reports

  12. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    (6) gravitational lenses (6) uvea (6) brain (5) comparative evaluations (5) fluids (5) ... Regulation of brain copper homeostasis by the brain barrier systems: Effects of ...

  13. News Item

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    kickstart innovative but risky brain research. The partnership hopes to yield discoveries that accelerate President Barack Obama's national BRAIN (Brain Research through ...

  14. R&D100 Winners * Impacts on Global...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... the physics of materials properties into a form more manageable for the human brain. Silicon brain assists comprehension by carbon-based brain, which reciprocates by finding ways ...

  15. SSRL HEADLINES Nov 2006

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Contents of this Issue: Science Highlight - Untangling Brain Disease Science Highlight - ... 1. Science Highlight - Untangling Brain Disease (contacts: X. Wang, ...

  16. Panofsky Agonisters: 1950 Loyalty Oath at Berkeley; Pief navigates the crisis

    SciTech Connect (OSTI)

    Jackson, John David

    2008-08-14

    In 1949-1951 the University of California was traumatized and seriously damaged by a Loyalty Oath controversy. Wolfgang K. H. Panofsky, a young and promising physics professor and researcher at Lawrence's Radiation Laboratory, was caught up in the turmoil.

  17. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    DOE Patents [OSTI]

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  18. SU-E-T-225: It Is Necessary to Contouring the Brainstem On MRI Images in Radiotherapy of Head and Neck Cancer

    SciTech Connect (OSTI)

    Gong, G; Liu, C; Liu, C

    2014-06-01

    Purpose: To analyze the error in contouring the brainstem for patients with head and neck cancer who underwent radiotherapy based on computed tomography (CT) and magnetic resonance (MR) images. Methods: 20 brain tumor and 17 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. For each patient, one observer contoured the brainstem on CT and MR images for 10 times, and 10 observers from five centers delineated the brainstem on CT and MR images only one time. The inter- and intra-observers volume and outline variations were compared. Results: The volumes of brainstem contoured by inter- and intra-observers on CT and MR images were similar (p>0.05). The reproducibility of contouring brainstem on MR images was better than that on CT images (p<0.05) for both inter- and intra-observer variability. The inter- and intra-observer for contouring on CT images reached mean values of 0.810.05 (p>0.05) and of 0.850.05 (p>0.05), respectively, while on MR images these respective values were 0.900.05 (p>0.05) and 0.920.04 (p>0.05). Conclusion: Contouring the brainstem on MR images was more accurate and reproducible than that on CT images. Precise information might be more helpful for protecting the brainstem radiation injury the patients whose lesion were closed to brainstem.

  19. Type A Accident Investigation Board Report on the January 17, 1996, Electrical Accident With Injury in Building 209, Technical Area 21, Tritium Science and Fabrication Facility, Los Alamos National Laboratory

    Office of Energy Efficiency and Renewable Energy (EERE)

    This report is an independent product of the Type A Accident Investigation Board appointed by Tara O’Toole, M.D., M.P.H., Assistant Secretary for Environment, Safety and Health (EH-1).

  20. Type B Accident Investigation Board Report on the March 26, 1999, Worker Injury at the East Tennessee Technology Park Three-Building Decontamination and Decommissioning and Recycle Project Site

    Broader source: Energy.gov [DOE]

    This report is an independent product of the Type B Investigation Board appointed by Steven D. Richardson, Acting Manager, Oak Ridge Operations Office, U.S. Department of Energy (DOE). The Board was appointed to perform a Type B investigation of these incidents and to prepare an investigation report in accordance with DOE Order 225.1A, Accident Investigations.

  1. Type A Accident Investigation Board Report of the July 28, 1998, Fatality and Multiple Injuries Resulting from Release of Carbon Dioxide at Building 648, Test Reactor Area, Idaho National Engineering and Environmental Laboratory

    Broader source: Energy.gov [DOE]

    This report is an independent product of the Type A Accident Investigation Board appointed by Peter N. Brush, Acting Assistant Secretary for Environment, Safety and Health (EH-1).

  2. Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1953-1970: Description of individual studies, data files, codes, and summaries of significant findings

    SciTech Connect (OSTI)

    Grahn, D.; Fox, C.; Wright, B.J.; Carnes, B.A.

    1994-05-01

    Between 1953 and 1970, studies on the long-term effects of external x-ray and {gamma} irradiation on inbred and hybrid mouse stocks were carried out at the Biological and Medical Research Division, Argonne National Laboratory. The results of these studies, plus the mating, litter, and pre-experimental stock records, were routinely coded on IBM cards for statistical analysis and record maintenance. Also retained were the survival data from studies performed in the period 1943-1953 at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The card-image data files have been corrected where necessary and refiled on hard disks for long-term storage and ease of accessibility. In this report, the individual studies and data files are described, and pertinent factors regarding caging, husbandry, radiation procedures, choice of animals, and other logistical details are summarized. Some of the findings are also presented. Descriptions of the different mouse stocks and hybrids are included in an appendix; more than three dozen stocks were involved in these studies. Two other appendices detail the data files in their original card-image format and the numerical codes used to describe the animal`s exit from an experiment and, for some studies, any associated pathologic findings. Tabular summaries of sample sizes, dose levels, and other variables are also given to assist investigators in their selection of data for analysis. The archive is open to any investigator with legitimate interests and a willingness to collaborate and acknowledge the source of the data and to recognize appropriate conditions or caveats.

  3. News | Argonne National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    News No one has yet imaged an entire brain down to the level of individual cells; but ... Full Story Bobby Kasthuri wants to map the human brain. Unlike most brain researchers, ...

  4. Workers at Paducah Site Exceed 1.5 Million Hours Without Lost...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    at Paducah Site Exceed 1.5 Million Hours Without Lost-Time Injury, Illness Workers at Paducah Site Exceed 1.5 Million Hours Without Lost-Time Injury, Illness October 30, 2014 -...

  5. B O N N E V I L L E P O W E R A D M I N I S T R A T I O N Collective

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    or dirty 1-2. INJURY AND DEATH BENEFITS 1-2.01 Benefits will be provided by the United States for the disability or death of an employee resulting from personal injuries...

  6. Type B Accident Investigation of the January 10, 2006, Flash...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    January 10, 2006, Flash Fire and Injury at the Savannah River National Laboratory Type B Accident Investigation of the January 10, 2006, Flash Fire and Injury at the Savannah River...

  7. Freedom of Information Act Response

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    You will have to assume risk of loss, or injury result from. your use of BPA's prop , -for such loss, or injury for which BPA may be responsible under the pmAom of the...

  8. Oak Ridge Associated Universities Procurement Questionnaire Applicatio...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Occupational Medical Surveillance System (OMSS) PIA, Idaho National Laboratory Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System ...

  9. Occupational Medical Surveillance System (OMSS) PIA, Idaho National...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    (OMSS) PIA, Idaho National Laboratory More Documents & Publications Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System ...

  10. Electronic DOE Information Security System (eDISS) PIA, Office...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Integrated Safety Management Workshop Registration, PIA, Idaho National Laboratory Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness ...

  11. Federal Radiological Monitoring and Assessment Center | National...

    National Nuclear Security Administration (NNSA)

    for radiation injuries. In support of field operations the FRMAC provides geographic information systems, communications, mechanical, electrical, logistics and administrative...

  12. Electronic DOE Information Security System (eDISS) PIA, Office...

    Energy Savers [EERE]

    Safety Management Workshop Registration, PIA, Idaho National Laboratory Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  13. Occupational Medical Surveillance System (OMSS) PIA, Idaho National...

    Energy Savers [EERE]

    (OMSS) PIA, Idaho National Laboratory More Documents & Publications Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  14. Oak Ridge Associated Universities Procurement Questionnaire Applicatio...

    Energy Savers [EERE]

    Medical Surveillance System (OMSS) PIA, Idaho National Laboratory Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  15. Employee Job Task Analysis (EJTA) PIA, Richland Operations Office...

    Energy Savers [EERE]

    (EJTA) PIA, Richland Operations Office More Documents & Publications Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  16. Cyborge Reporting Solution, PIA, Bechtel Jacobs Company LLC ...

    Energy Savers [EERE]

    More Documents & Publications Medgate, PIA, Bechtel Jacobs Company, LLC Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  17. Carlsbad Industrial Safety and Health PIA, Carlsbad Field Offce...

    Energy Savers [EERE]

    Safety Management Workshop Registration, PIA, Idaho National Laboratory Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System...

  18. ORISE: How to Work With Us | Worker Health Studies

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    environmental health. Services provided include illness and injury surveillance, worker health research, medical data management, beryllium exposure studies and testing,...

  19. Type B Accident Investigation Board Report of the Savannah River Site Hand

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Injury at the Salt Waste Processing Facility on October 6, 2009 | Department of Energy Savannah River Site Hand Injury at the Salt Waste Processing Facility on October 6, 2009 Type B Accident Investigation Board Report of the Savannah River Site Hand Injury at the Salt Waste Processing Facility on October 6, 2009 November 1, 2009 This report documents the results of the Type B Accident Investigation Board (Board) investigation of the October 6, 2009, hand injury at the Department of Energy

  20. EERE Success Story—New Report States That Hydrokinetic Turbines Have Minimal Environmental Impacts on Fish

    Broader source: Energy.gov [DOE]

    EERE has released a report assessing likelihood of fish injury and mortality from the operation of hydrokinetic turbines.

  1. Dashboards | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Dashboards Dashboards Public Final Occurrence Reports: Searchable information on DOE's Final Occurrence Reports since 2005, available to the public and updated daily. Computerized Accident Incident Reporting System (CAIRS) - Injury and Illness Dashboard: The Injury and Illness Dashboard is a tool that allows users to easily explore DOE occupational safety and health injury and illness information. Its features include: Graphical and tabular depictions of injury and illness information Calendar

  2. Scientists call for unified initiative to advance microbiome...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    will create the infrastructure to come together under a single umbrella," Gilbert said. The initiative is modeled after the BRAIN Initiative (Brain Research through...

  3. ega3322.tmp

    Office of Scientific and Technical Information (OSTI)

    activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists...

  4. Molecular Foundry

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab; Professor of Physics UC Berkeley 66 Auditorium 9:30 am Keynote Address The BRAIN Initiative and Nanoscience abstract Ralph Greenspan Director, Center for Brain...

  5. Neuroligin and Neurexins - Autism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cells in the brain that enable signals to be transmitted. Neurexin and neuroligins are proteins that associate in the extracellular space between synapses in the brain, and they ...

  6. Michael E. Phelps, 1998 | U.S. DOE Office of Science (SC)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of the living, developing or aging brain and heart muscle, as well as the altered ... between neuronal systems in the brain as well as the alteration of neuronal ...

  7. ALSNews Vol. 367

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    A Designed Protein Maps Brain Activity Scientists designed and validated via crystallographic studies a fluorescent protein that allows the permanent marking of active brain cells. ...

  8. ALSNews Vol. 368

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the Brain Scientists working at the ALS recently solved the crystallographic structures of several amine transporters in an effort to better understand why the human brain ...

  9. Portsmouth and Paducah Construction Workers Needs Assessment

    Office of Environmental Management (EM)

    ... however, there was suggestion of an association between mercury exposure and brain cancer. ... Brain cancer has been associated with solvents and metal machining operations and among ...

  10. A New Computational Paradigm in Multiscale Simulations: Application...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    New Computational Paradigm in Multiscale Simulations: Application to Brain Blood Flow ... We study blood flow in a patient-specific cerebrovasculature with a brain aneurysm, and ...

  11. SSRL HEADLINES - September 2011

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Invention Measures Stroke Damage in the Brain Science Feature - Scientists Get First ... Invention Measures Stroke Damage in the Brain (SLAC News Center article by Glennda Chui) ...

  12. News Item

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ralph Greenspan, UCSD Professor of Neurobiology and Director of the Center for Brain Activity Mapping, gave the first of three keynote addresses, discussing the BRAIN initiative ...

  13. SSRL HEADLINES May 2001

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Highlights SSRL Faculty Research on Brain Communications Welch Foundation Visit WHO ... Highlights SSRL Faculty Research on Brain Communications Professor Axel Brunger's ...

  14. SSRL HEADLINES May 2009

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science Highlight - Visualizing Brain Metals in Health and Disease Science ... 2. Science Highlight - Visualizing Brain Metals in Health and Disease (contact: H. ...

  15. Positive Vibes

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    but treat-just about every manner of debilitating brain condition commonly known. ... Then he turned his attention to the human brain. Initially, Sinha showed that he could ...

  16. Structure of Synaptic Connectors Solved

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    called synapses is critical for proper brain function, and errors in the process are ... autism is a developmental disorder of the brain that impairs social interactions and ...

  17. Brainwaves as a Biometric Parameter for Unique Identification...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    The method uses brain wave data uniquely formed from an individual's thought process. The brain waves are sampled using EEG equipment and processed using phase-space distribution ...

  18. Faces of Science: Michelle Espy

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    At Los Alamos, Michelle and her team have developed SQUIDs (Superconducting Quantum Interference Devices) to measure brain function, image brain features, and detect liquid bombs. ...

  19. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the optic nerve and, ultimately, the brain, which perceives patterns of light ... to map the human brain function stimulated by the devices or by normal biological vision. ...

  20. News Releases - 2015

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    magnetic resonance imaging to create images of injured soft tissues, such as the brain. ... of injured soft tissues, such as the brain. - 122015 Los Alamos National Laboratory ...

  1. Positive Vibes

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    brain disorders November 13, 2015 Positive Vibes Los Alamos's Dipen Sinha has developed a specialized technique for using sound waves to stimulate neurons in key brain ...

  2. Roadrunner supercomputer puts research at a new scale

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Code run on the machine mimics brain mechanisms underlying human sight LOS ALAMOS, New ... Neurons are nerve cells that process information in the brain. Neurons communicate with ...

  3. Faces of Science: Michelle Espy

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to develop sensitive magnetic sensors that measure brain function and detect liquid bombs. ... to develop sensitive magnetic sensors that measure brain function and detect liquid bombs. ...

  4. Search Method for Real-time Knowledge Discovery Modeled on the...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Search Method for Real-time Knowledge Discovery Modeled on the Human Brain Oak Ridge ... information processing properties of the human brain to computational knowledge discovery. ...

  5. Cornell dots research collaboration leads to $10M cancer center...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    at MSKCC in New York City - will focus on melanoma (skin) and malignant brain cancers. ... Assessment of particles in brain tumors for cancer therapy. C dots successfully have ...

  6. A Standard for Neuroscience Data

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    GE, Janelia Farm, Allen Institute for Brain Science and the International ... The computational tools could also help facilitate the White House's Brain Research ...

  7. Magnetic Resonance Imaging at Princeton, UofV, and UNH | U.S...

    Office of Science (SC) Website

    imaging of lungs, heart, and possibly the brain, possible imaging of astronauts ... expectations that detailed images of the brain or other organs might also be possible. ...

  8. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    June 12, 2008 Code run on the machine mimics brain mechanisms underlying human sight LOS ... Neurons are nerve cells that process information in the brain. Neurons communicate with ...

  9. SSRL HEADLINES September 2007

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cells in the brain that enable signals to be transmitted. Neurexin and neuroligins are proteins that associate in the extracellular space between synapses in the brain, and they ...

  10. Browse by Discipline -- E-print Network Subject Pathways: Physics...

    Office of Scientific and Technical Information (OSTI)

    ... Jong Chul -Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technolog(e, Jong Chul -Department of Bio and Brain Engineering, Korea Advanced ...

  11. Natural lipid extracts and biomembrane-mimicking lipid compositions...

    Office of Scientific and Technical Information (OSTI)

    found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). ... AND INFORMATION SCIENCE; BINDING ENERGY; BRAIN; CAPACITY; CATTLE; CHARGE DENSITY; ...

  12. TechLab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Find out more about our latest exhibit Climate Prisms: The Arctic. Explore: Temporary Exhibit: Los Alamos Technology on Mars Brain Games: Puzzles to exercise your brain Play area ...

  13. at Los Alamos National Laboratory's Bradbury Science Museum

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Brain teasers traveling exhibit opens at Los Alamos National Laboratory's Bradbury Science Museum December 4, 2008 LOS ALAMOS, New Mexico, December 4, 2008- "Brain Teasers," a ...

  14. Science Magazine Articles | Argonne National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science Magazine Articles "Second Bid for Brain Observatory," by Emily Underwood Science, ... bold proposal: the creation of a National Brain Observatory, a network of neurotechnology ...

  15. Faces of Science

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ironically Ulam developed the Monte Carlo method while recovering from brain inflammation. ... to develop sensitive magnetic sensors that measure brain function and detect liquid bombs. ...

  16. Browse by Discipline -- E-print Network Subject Pathways: Materials...

    Office of Scientific and Technical Information (OSTI)

    J. O'Toole) - School of Behavioral and Brain Sciences, University of Texas at Dallas ... Oliva, Aude (Aude Oliva) - Department of Brain and Cognitive Science, Massachusetts ...

  17. LANL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    but treat-just about every manner of debilitating brain condition commonly known. ... Then he turned his attention to the human brain. 32 1663 October 2015 Initially, Sinha ...

  18. Computational Method for Improved Forewarning of Critical Events...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    human brain waves and chest sounds, motors, and electrical devices. Examples of possible biomedical forewarning include distinguishing between preseizure and nonseizure brain ...

  19. Differences in Brainstem Fiber Tract Response to Radiation: A Longitudinal Diffusion Tensor Imaging Study

    SciTech Connect (OSTI)

    Uh, Jinsoo; Merchant, Thomas E.; Li, Yimei; Feng, Tianshu; Gajjar, Amar; Ogg, Robert J.; Hua, Chiaho

    2013-06-01

    Purpose: To determine whether radiation-induced changes in white matter tracts are uniform across the brainstem. Methods and Materials: We analyzed serial diffusion tensor imaging data, acquired before radiation therapy and over 48 to 72 months of follow-up, from 42 pediatric patients (age 6-20 years) with medulloblastoma. FSL software (FMRIB, Oxford, UK) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivities. For a consistent identification of volumes of interest (VOIs), the parametric maps of each patient were transformed to a standard brain space (MNI152), on which we identified VOIs including corticospinal tract (CST), medial lemniscus (ML), transverse pontine fiber (TPF), and middle cerebellar peduncle (MCP) at the level of pons. Temporal changes of DTI parameters in VOIs were compared using a linear mixed effect model. Results: Radiation-induced white matter injury was marked by a decline in FA after treatment. The decline was often accompanied by decreased axial diffusivity, increased radial diffusivity, or both. This implied axonal damage and demyelination. We observed that the magnitude of the changes was not always uniform across substructures of the brainstem. Specifically, the changes in DTI parameters for TPF were more pronounced than in other regions (P<.001 for FA) despite similarities in the distribution of dose. We did not find a significant difference among CST, ML, and MCP in these patients (P>.093 for all parameters). Conclusions: Changes in the structural integrity of white matter tracts, assessed by DTI, were not uniform across the brainstem after radiation therapy. These results support a role for tract-based assessment in radiation treatment planning and determination of brainstem tolerance.

  20. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    SciTech Connect (OSTI)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (?) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (?), myo-Inositol (mIns) and Asp (?), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (?). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.

  1. Type A Accident Investigation of the June 21, 2001, Drilling Rig Operator

    Energy Savers [EERE]

    Injury at the Fermi National Accelerator Laboratory, August 2001 | Department of Energy June 21, 2001, Drilling Rig Operator Injury at the Fermi National Accelerator Laboratory, August 2001 Type A Accident Investigation of the June 21, 2001, Drilling Rig Operator Injury at the Fermi National Accelerator Laboratory, August 2001 August 8, 2001 On June 21, 2001, at approximately 9:40 A.M., a construction sub-tier contractor employee (the "Operator") at the Fermi National Accelerator

  2. Type B Accident Investigation At Washington Closure Hanford, LLC, Employee

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Fall Injury on July 1, 2009, At The 336 Building, Hanford Site, Washington | Department of Energy At Washington Closure Hanford, LLC, Employee Fall Injury on July 1, 2009, At The 336 Building, Hanford Site, Washington Type B Accident Investigation At Washington Closure Hanford, LLC, Employee Fall Injury on July 1, 2009, At The 336 Building, Hanford Site, Washington July 30, 2009 During D4 project demolition preparation work on the morning of July 1, 2009, in Hanford's 300 Area, a millwright

  3. Type B Accident Investigation Board Report for the January 11, 2006,

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Personal Injury During Table Saw Use at the Heyrend Way Facility, Idaho Falls, Idaho | Department of Energy for the January 11, 2006, Personal Injury During Table Saw Use at the Heyrend Way Facility, Idaho Falls, Idaho Type B Accident Investigation Board Report for the January 11, 2006, Personal Injury During Table Saw Use at the Heyrend Way Facility, Idaho Falls, Idaho February 10, 2006 An accident at the Idaho National Laboratory (INL) was investigated in which a technician sustained a

  4. Type B Accident Investigation Board Report of the Bechtel Jacobs Company,

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    LLC Employee Fall Injury on January 3, 2006, at the K-25 Building, East Tennessee Technology Park, Oak Ridge, Tennessee | Department of Energy Bechtel Jacobs Company, LLC Employee Fall Injury on January 3, 2006, at the K-25 Building, East Tennessee Technology Park, Oak Ridge, Tennessee Type B Accident Investigation Board Report of the Bechtel Jacobs Company, LLC Employee Fall Injury on January 3, 2006, at the K-25 Building, East Tennessee Technology Park, Oak Ridge, Tennessee February 10,

  5. Type B Accident Investigation Board Report of the Brookhaven National

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Laboratory Employee Injury at Building 1005H on October 9, 2009 | Department of Energy of the Brookhaven National Laboratory Employee Injury at Building 1005H on October 9, 2009 Type B Accident Investigation Board Report of the Brookhaven National Laboratory Employee Injury at Building 1005H on October 9, 2009 December 11, 2009 On the afternoon of October 9, 2009, a Lead Rigger for Brookhaven Science Associates (BSA), LLC at the Brookhaven National laboratory (BNL) wasinjured while at the

  6. Type B Accident Investigation Board Report on the October 15, 2001, Grout

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Injection Operator Injury at the Cold Test Pit South, Idaho National Engineering and Environmental Laboratory | Department of Energy 15, 2001, Grout Injection Operator Injury at the Cold Test Pit South, Idaho National Engineering and Environmental Laboratory Type B Accident Investigation Board Report on the October 15, 2001, Grout Injection Operator Injury at the Cold Test Pit South, Idaho National Engineering and Environmental Laboratory November 13, 2001 On October 15, 2001, at

  7. Type B Accident Investigation Board Report on the October 8, 2004, Grounds

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Worker Injury at the Pacific Northwest National Laboratory | Department of Energy 8, 2004, Grounds Worker Injury at the Pacific Northwest National Laboratory Type B Accident Investigation Board Report on the October 8, 2004, Grounds Worker Injury at the Pacific Northwest National Laboratory November 22, 2004 On October 8, 2004, at approximately 11:00 am, a Grounds Worker at the Pacific Northwest National laboratory (PNNL) fell from a Toro Workman 3200 Utility Vehicle and fracturedhis right

  8. Investigation of the March 5, 2011, Building 488, Brookhaven National

    Office of Environmental Management (EM)

    Laboratory, Tree Felling Injury | Department of Energy March 5, 2011, Building 488, Brookhaven National Laboratory, Tree Felling Injury Investigation of the March 5, 2011, Building 488, Brookhaven National Laboratory, Tree Felling Injury April 2011 On Saturday, March 5, 2011 at approximately 10:20 a.m., a Brookhaven National Laboratory Building and Grounds Utility Worker was felling a pine tree while elevated in a 60-foot articulating and telescoping boom lift approximately 20-feet above the

  9. Oak Ridge Office SharePoint( MicrosoftSHarePointServer) PIA,...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory Integrated Safety Management Workshop Registration, PIA, Idaho National Laboratory Occupational Medicine ...

  10. Employee Job Task Analysis (EJTA) PIA, Richland Operations Office...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    More Documents & Publications Occupational Medicine - Assistant PIA, Idaho National Laboratory Occupational Injury & Illness System (01&15) PIA, Idaho National Laboratory PIA - ...

  11. Occupational Medicine | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    state regulations. The Occupational Medicine office enhances the efficiency of existing safety and health programs and assists in the reduction of workplace injuries and illnesses....

  12. ORISE Resources: Radiological and Nuclear Terrorism: Medical...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to mass casualties that may involve radiological injuries. The interactive, two-hour training, titled Radiological and Nuclear Terrorism: Medical Response to Mass Casualties...

  13. Avian and Bat Assessment at the Lewes Wind Turbine

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Fish & Wildlife Service-USFWS), Julie Thompson (USFWS), Holly Niederriter (Delaware ... cause of deathvisible injuries, and estimated time of death (e.g., <1day, <2 days). ...

  14. Type B Accident Investigation of the Savannah River Site Arc...

    Broader source: Energy.gov (indexed) [DOE]

    Type B Accident Investigation Board investigation of the September 23, 2009, employee burn injury at the Department of Energy (DOE) Savannah River Site (SRS) D Area powerhouse....

  15. Type A Accident Investigation of the June 21, 2001, Drilling...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    June 21, 2001, Drilling Rig Operator Injury at the Fermi National Accelerator Laboratory, August 2001 Type A Accident Investigation of the June 21, 2001, Drilling Rig Operator ...

  16. Microsoft Word - Los Alamos National Security, LLC_SUPP DISABILITY...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    injury. This highlight sheet is an overview of your Supplemental Disability Insurance. Once a group policy is issued to your employer, a certificate of Insurance will be available...

  17. Operating Experience Summary- 2012-02 – May 11, 2012

    Broader source: Energy.gov [DOE]

    Inside this issue: Improper Use of Dewar Carts Results in Serious Hand Injuries - Page 1 Strategic Petroleum Reserve Investigation Results - Fatality at the Bryan Mound Site - Page 5

  18. Chapter 4: Advancing Clean Electric Power Technologies | Hydropower...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    more flexible, more fish-friendly, and capable of aeration to improve water quality. ... enhancements to reduce injury to fish and aeration into turbine flow passages to ...

  19. Sandia Energy - EC, DHS's S&T Directorate, Federal Emergency...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that must be dealt with quickly and effectively in order to minimize injury and loss of life. Simulating such events before they occur can help emergency responders...

  20. Microsoft Word - Los Alamos National Security, LLC_Non-Cont STD...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Due to accidental bodily injury, sickness, mental illness, substance abuse or pregnancy you are unable to perform the essential duties of your occupation, and as a result,...