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Title: Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

Abstract

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, andmore » baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.« less

Authors:
;  [1];  [2];  [1];  [2]; ; ; ;  [1]; ;  [2];  [2];  [3];  [2];  [4];  [1]
  1. Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)
  2. Department of Radiology, University of California, San Diego, La Jolla, California (United States)
  3. (United States)
  4. Department of Psychiatry, University of California, San Diego, La Jolla, California (United States)
Publication Date:
OSTI Identifier:
22645762
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ATROPHY; BIOLOGICAL MARKERS; BIOMEDICAL RADIOGRAPHY; CLINICAL TRIALS; COMPUTER CODES; GY RANGE 01-10; GY RANGE 10-100; HIPPOCAMPUS; IMAGES; IN VIVO; MULTIVARIATE ANALYSIS; NEOPLASMS; NMR IMAGING; PATIENTS; RADIATION DOSES; RADIATION EFFECTS; RADIOTHERAPY

Citation Formats

Seibert, Tyler M., Karunamuni, Roshan, Bartsch, Hauke, Kaifi, Samar, Krishnan, Anitha Priya, Dalia, Yoseph, Burkeen, Jeffrey, Murzin, Vyacheslav, Moiseenko, Vitali, Kuperman, Joshua, White, Nathan S., Brewer, James B., Department of Neurosciences, University of California, San Diego, La Jolla, California, Farid, Nikdokht, McDonald, Carrie R., and Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.035.
Seibert, Tyler M., Karunamuni, Roshan, Bartsch, Hauke, Kaifi, Samar, Krishnan, Anitha Priya, Dalia, Yoseph, Burkeen, Jeffrey, Murzin, Vyacheslav, Moiseenko, Vitali, Kuperman, Joshua, White, Nathan S., Brewer, James B., Department of Neurosciences, University of California, San Diego, La Jolla, California, Farid, Nikdokht, McDonald, Carrie R., & Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging. United States. doi:10.1016/J.IJROBP.2016.10.035.
Seibert, Tyler M., Karunamuni, Roshan, Bartsch, Hauke, Kaifi, Samar, Krishnan, Anitha Priya, Dalia, Yoseph, Burkeen, Jeffrey, Murzin, Vyacheslav, Moiseenko, Vitali, Kuperman, Joshua, White, Nathan S., Brewer, James B., Department of Neurosciences, University of California, San Diego, La Jolla, California, Farid, Nikdokht, McDonald, Carrie R., and Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu. Wed . "Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging". United States. doi:10.1016/J.IJROBP.2016.10.035.
@article{osti_22645762,
title = {Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging},
author = {Seibert, Tyler M. and Karunamuni, Roshan and Bartsch, Hauke and Kaifi, Samar and Krishnan, Anitha Priya and Dalia, Yoseph and Burkeen, Jeffrey and Murzin, Vyacheslav and Moiseenko, Vitali and Kuperman, Joshua and White, Nathan S. and Brewer, James B. and Department of Neurosciences, University of California, San Diego, La Jolla, California and Farid, Nikdokht and McDonald, Carrie R. and Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu},
abstractNote = {Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.},
doi = {10.1016/J.IJROBP.2016.10.035},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}
  • A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computedmore » tomography.« less
  • Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodesmore » by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.« less
  • Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex formore » each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.« less
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