title: White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice.
abstract: OBJECTIVE
  Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species.
  
  
  METHODS
  Patients were imaged with T1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7-) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups.
  
  
  RESULTS
  WM volume was significantly decreased following treatment in 7- and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7- group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb.
  
  
  CONCLUSIONS
  Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.
authors.affiliation: Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada. Electronic address: brian.nieman@utoronto.ca.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nieman
authors.affiliation: Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A Elizabeth
authors.initials: AE
authors.lastname: de Guzman
authors.affiliation: Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Gazdzinski
authors.affiliation: Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada; Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Kimel Family Translational Imaging Genetics Research Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Jon
authors.initials: J
authors.lastname: Pipitone
authors.affiliation: Alberta Children's Hospital, Calgary, Alberta, Canada; Departments of Oncology and Pediatrics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Douglas
authors.initials: D
authors.lastname: Strother
authors.affiliation: Division of Oncology/Hematology/BMT British Columbia Children's Hospital and British Columbia Women's Hospital and Health Centre, Vancouver, British Columbia, Canada; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Fryer
authors.affiliation: Department of Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.affiliation: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Laughlin
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Normand
authors.initials: N
authors.lastname: Laperriere
authors.affiliation: Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lily
authors.initials: L
authors.lastname: Riggs
authors.affiliation: Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Jovanka
authors.initials: J
authors.lastname: Skocic
authors.affiliation: Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Mabbott
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology / Q000528:radiation effects; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects*; D066128:Gray Matter / Q000473:pathology / Q000528:radiation effects*; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D012189:Retrospective Studies; D013997:Time Factors; D066127:White Matter / Q000473:pathology / Q000528:radiation effects*