title: Radiation-induced cognitive impairment and altered diffusion tensor imaging in a juvenile rat model of cranial radiotherapy.
abstract: OBJECTIVE
  To assess the long-term effects of fractionated whole brain irradiation (fWBI) using diffusion tensor imaging (DTI) and behavior in a pediatric rodent model for the clinical presentation of adult pediatric cancer survivors.
  
  
  METHODS
  Five-week-old, male F344xBN rats were randomized to receive 0, 5, or 6.5 Gy fractions biweekly for 3 weeks, resulting in Sham, Irradiated-30 (IR-30) and IR-39 Gy total dose groups. Magnetic Resonance Imaging occurred at 1, 3, 6 and 9 months with behavioral assessment at 10-11 months post-fWBI.
  
  
  RESULTS
  Irradiation reduced brain size (p < 0.001) and body weight (p < 0.001) proportionate to dose. At 1 month post-fWBI and throughout follow-up, diffusion was reduced in IR-30 and IR-39 relative to shams (p < 0.001). IR-30 but not IR-39 rats were impaired relative to Shams on the reversal trial of the Morris Water Maze (p < 0.05), and IR-30 rats preferred a striatum- mediated strategy (p < 0.06).
  
  
  CONCLUSIONS
  Hippocampal performance was impaired in IR-30 but not IR-39 animals. While gross size differences exist, white matter integrity is preserved in rats after fWBI at 5 weeks. This significant departure from childhood cancer survivors and single fraction rodent studies where white matter degradation is a prominent feature are discussed.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine , Winston-Salem, NC.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Peiffer
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Creer
authors.forename: Constance
authors.initials: C
authors.lastname: Linville
authors.forename: John
authors.initials: J
authors.lastname: Olson
authors.forename: Praveen
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Jacquelyn Ann
authors.initials: JA
authors.lastname: Brown
authors.forename: David R
authors.initials: DR
authors.lastname: Riddle
authors.forename: Mike E
authors.initials: ME
authors.lastname: Robbins
authors.forename: Judy E
authors.initials: JE
authors.lastname: Brunso-Bechtold
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D001921:Brain / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000532:radiotherapy; D003071:Cognition / Q000528:radiation effects*; D056324:Diffusion Tensor Imaging; D019583:Dose Fractionation, Radiation; D006624:Hippocampus / Q000528:radiation effects; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D023421:Models, Animal; D011878:Radiotherapy / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
keywords: MRI; Rat; brain; fractionated whole-brain irradiation; pediatric