title: Radiation-induced alterations in mouse brain development characterized by magnetic resonance imaging.
abstract: OBJECTIVE
  The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI).
  
  
  METHODS
  Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation.
  
  
  RESULTS
  Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone.
  
  
  CONCLUSIONS
  MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Gazdzinski
authors.forename: Kyle
authors.initials: K
authors.lastname: Cormier
authors.forename: Fred G
authors.initials: FG
authors.lastname: Lu
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.forename: C Shun
authors.initials: CS
authors.lastname: Wong
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nieman
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D001931:Brain Mapping / Q000379:methods*; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000502:physiology / Q000528:radiation effects; D058953:Neural Stem Cells / Q000502:physiology / Q000528:radiation effects; D009929:Organ Size / Q000528:radiation effects