title: Dose-dependent white matter damage after brain radiotherapy.
abstract: Brain radiotherapy is limited in part by damage to white matter, contributing to neurocognitive decline. We utilized diffusion tensor imaging (DTI) with multiple b-values (diffusion weightings) to model the dose-dependency and time course of radiation effects on white matter.
  
  
  
  Fifteen patients with high-grade gliomas treated with radiotherapy and chemotherapy underwent MRI with DTI prior to radiotherapy, and after months 1, 4-6, and 9-11. Diffusion tensors were calculated using three weightings (high, standard, and low b-values) and maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ∥), and radial diffusivity (λ⊥) were generated. The region of interest was all white matter.
  
  
  
  MD, λ∥, and λ⊥increased significantly with time and dose, with corresponding decrease in FA. Greater changes were seen at lower b-values, except for FA. Time-dose interactions were highly significant at 4-6months and beyond (p<.001), and the difference in dose response between high and low b-values reached statistical significance at 9-11months for MD, λ∥, and λ⊥(p<.001, p<.001, p=.005 respectively) as well as at 4-6months for λ∥(p=.04).
  
  
  
  We detected dose-dependent changes across all doses, even <10Gy. Greater changes were observed at low b-values, suggesting prominent extracellular changes possibly due to vascular permeability and neuroinflammation.
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Michael
authors: M
authors: Connor
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Roshan
authors: R
authors: Karunamuni
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States; Department of Psychiatry, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Carrie
authors: C
authors: McDonald
authors: Department of Radiology, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Nathan
authors: N
authors: White
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Niclas
authors: N
authors: Pettersson
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Vitali
authors: V
authors: Moiseenko
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Tyler
authors: T
authors: Seibert
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Deborah
authors: D
authors: Marshall
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Laura
authors: L
authors: Cervino
authors: Department of Radiology, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Hauke
authors: H
authors: Bartsch
authors: Department of Radiology, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Joshua
authors: J
authors: Kuperman
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States.
authors: Vyacheslav
authors: V
authors: Murzin
authors: Department of Radiology, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Anitha
authors: A
authors: Krishnan
authors: Department of Radiology, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Nikdokht
authors: N
authors: Farid
authors: Department of Radiology, University of California San Diego, United States; Department of Psychiatry, University of California San Diego, United States; Department of Neurosciences, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States.
authors: Anders
authors: A
authors: Dale
authors: Department of Radiation Medicine and Applied Sciences, University of California San Diego, United States; Multimodal Imaging Laboratory, University of California San Diego, United States. Electronic address: jhattangadi@ucsd.edu.
authors: Jona
authors: J
authors: Hattangadi-Gluth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D016371:Cranial Irradiation / Q000009:adverse effects*; D056324:Diffusion Tensor Imaging; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000528:radiation effects*
keywords: Diffusion tensor imaging; MRI; Radiation; Radiotherapy; White matter; b-Value