title: Radiation Dose-Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Seibert
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Roshan
authors.initials: R
authors.lastname: Karunamuni
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Hauke
authors.initials: H
authors.lastname: Bartsch
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Samar
authors.initials: S
authors.lastname: Kaifi
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Anitha Priya
authors.initials: AP
authors.lastname: Krishnan
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Dalia
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Burkeen
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Murzin
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Vitali
authors.initials: V
authors.lastname: Moiseenko
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kuperman
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: White
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.
authors.forename: James B
authors.initials: JB
authors.lastname: Brewer
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Nikdokht
authors.initials: N
authors.lastname: Farid
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California. Electronic address: jhattangadi@ucsd.edu.
authors.forename: Jona A
authors.initials: JA
authors.lastname: Hattangadi-Gluth
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001284:Atrophy / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008875:Middle Aged; D015999:Multivariate Analysis; D009929:Organ Size / Q000528:radiation effects; D012189:Retrospective Studies; D013997:Time Factors