title: Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation.
abstract: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development.
  
  
  
  Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing.
  
  
  
  Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI.
  
  
  
  The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Advanced Imaging Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California; Rudi Schulte Research Institute, Santa Barbara, California.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brown
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Advanced Imaging Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California; Rudi Schulte Research Institute, Santa Barbara, California.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Jun
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, California.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Cushman
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Christine
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Adam H
authors.initials: AH
authors.lastname: Beighley
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Johnny
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Kei
authors.initials: K
authors.lastname: Iwamoto
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Schaue
authors.affiliation: UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA Center for the Health Sciences, Los Angeles, California.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Harris
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, California.
authors.forename: James D
authors.initials: JD
authors.lastname: Jentsch
authors.affiliation: Advanced Imaging Laboratory, Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California; Rudi Schulte Research Institute, Santa Barbara, California.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bluml
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: wmcbride@mednet.ucla.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D003337:Corpus Callosum / Q000473:pathology* / Q000503:physiopathology* / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D008297:Male; D011829:Radiation Dosage; D051381:Rats; D011916:Rats, Inbred F344