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Title: SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams

Abstract

Purpose: To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research. Methods: The peak-to-valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac-induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X-ray microbeams this effect is evaded due to the quasi-instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulation being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center-to-center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm. Results: The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR wasmore » reduced by 16% at a depth of 10mm. Conclusion: For the pMRT beam the magnitude of cardiac-induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.« less

Authors:
;  [1]; ;  [2]
  1. University of Canterbury, Christchurch, Canterbury (New Zealand)
  2. University of Washington, Seattle, WA (United States)
Publication Date:
OSTI Identifier:
22649228
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; BEAMS; BRAIN; COMPUTERIZED SIMULATION; DOSE RATES; LINEAR ACCELERATORS; MONTE CARLO METHOD; PEAKS; RATS; X RADIATION

Citation Formats

Eagle, J, Marsh, S, Lee, E, and Meyer, J. SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams. United States: N. p., 2016. Web. doi:10.1118/1.4956859.
Eagle, J, Marsh, S, Lee, E, & Meyer, J. SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams. United States. doi:10.1118/1.4956859.
Eagle, J, Marsh, S, Lee, E, and Meyer, J. 2016. "SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams". United States. doi:10.1118/1.4956859.
@article{osti_22649228,
title = {SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams},
author = {Eagle, J and Marsh, S and Lee, E and Meyer, J},
abstractNote = {Purpose: To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research. Methods: The peak-to-valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac-induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X-ray microbeams this effect is evaded due to the quasi-instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulation being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center-to-center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm. Results: The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR was reduced by 16% at a depth of 10mm. Conclusion: For the pMRT beam the magnitude of cardiac-induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.},
doi = {10.1118/1.4956859},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: To investigate the dosimetric effects of collimator material on spatially modulated proton minibeams (pMBRT). Methods: pMBRT holds promise to exhibit shallow depth normal-tissue sparing effects similar to synchrotron based microbeams while also retaining potential for uniform dose distributions for tumor targets. TOPAS Monte Carlo simulations were performed for a 5cm thick multislit collimator with 0.3mm slits and 1mm center-to-center spacing for a 50.5MeV proton minibeam while varying collimator material between brass, tungsten, and iron. The collimator was placed both “flush” at the water phantom surface and at 5cm distance to investigate the effects on surface dose, peak-to-valley-dose-ratio (PVDR) andmore » neutron contribution. Results: For flush placement, the neutron dose at the phantom surface for the tungsten collimator was approximately 20% higher than for brass and iron. This was not reflected in the overall surface dose, which was comparable for all materials due to the relatively low neutron contribution of <0.1%. When the collimator was retracted, the overall neutron contribution was essentially identical for all three collimators. Surface dose dropped by ∼40% for all collimator materials with air gap compared to being flush with the phantom surface. This surface dose reduction was at the cost of increase in valley dose for all collimator materials due to increased angular divergence of the mini-beams at the surface and their consequent geometric penumbra at depth. When the collimator was placed at distance from the phantom surface the PVDR decreased. The peak-to-entrance-dose ratio was highest for the iron collimator with 5cm air gap. Conclusion: The dosimetric difference between the collimator materials is minimal despite the relatively higher neutron contribution at the phantom surface for the tungsten collimator when placed flush. The air gap between the collimator and phantom surface strongly influences all dosimetry parameters due to the influence of scatter on the narrow spatial modulation.« less
  • We present an analytic theory of well-developed pulsations in semiconductor lasers with a proton bombarded segment. A rate equation model is used with the proton bombarded region modeled as a fast saturable absorber. We obtain a closed form solution for the pulse shape, width, and energy, as well as the pulsation rate. The pulses can be as short as the diode roundtrip time ( about10 ps). A simple pulsation condition is derived; it agrees with the previously determined small signal instability criterion. Pulsation does not require absorber cross section larger than gain cross section.
  • Particle Induced X-ray Emission and proton microprobe analyses have been applied for the investigation of regional elemental distributions in connection with various pathological states in the brain. Malignant brain tumors and adjacent histologically intact tissue removed during surgery were analysed with PIXE. Systematic elemental variations, e.g., for calcium and selenium, were observed in the tumor front. The proton microprobe was applied to study the Ca and K concentrations in various cell strata in hippocampus following transient ischaemia in rat brain. Significant increases in the Ca level occurred in selectively vulnerable cells within 48 h after the ischaemia.
  • Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel{sup +} apoptosis but didmore » not dramatically affect PCNA{sup +} cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. - Highlights: • Typical neurodevelopmental defects could be observed in STZ-treated mouse fetuses. • Nrf2 played a crucial role in hyperglycaemia-induced brain malformations. • The effects of hyperglycaemia on neurons and glia cells were not same.« less
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