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Cerebral Cortex Advance Access published online on January 27, 2007

Cerebral Cortex, doi:10.1093/cercor/bhl168
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Developmental Changes and Injury Induced Disruption of the Radial Organization of the Cortex in the Immature Rat Brain Revealed by In Vivo Diffusion Tensor MRI

Stéphane V. Sizonenko1, Emily J. Camm1, Joel R. Garbow2, Stephane Maier3, Terrie E. Inder2, Chris E. Williams4, Jeffrey J. Neil2 and Petra S. Huppi1

1 Child Development Unit, Department of Paediatrics, School of Medicine, University of Geneva, Switzerland, 2 Mallinckrodt Institute of Radiology, Washington University Medical Centre, St Louis, USA, 3 Department of Radiology, Brigham's and Women's Hospital, Harvard Medical School, Boston, USA, 4 Liggins Institute, University of Auckland, Auckland, New Zealand

Address correspondence to Dr Stéphane V. Sizonenko, Unité de Développement, Hôpital des Enfants, 6 rue Willy Donzé, 1211 Geneva 14, Switzerland. Email: stephane.sizonenko{at}medecine.unige.ch.

During brain development, morphological changes modify the cortex from its immature radial organization to its mature laminar appearance. Applying in vivo diffusion tensor imaging (DTI), the microstructural organization of the cortex in the immature rat was analyzed and correlated to neurohistopathology. Significant differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were detected between the external (I–III) and deep (IV–VI) cortical layers in postnatal day 3 (P3) and P6 pups. With cortical maturation, ADC was reduced in both cortical regions, whereas a decrease in FA was only seen in the deep layers. A distinct radial organization of the external cortical layers with the eigenvectors perpendicular to the pial surface was observed at both ages. Histology revealed maturational differences in the cortical architecture with increased neurodendritic density and reduction in the radial glia scaffolding. Early DTI after hypoxia–ischemia at P3 shows reduced ADC and FA in the ipsilateral cortex that persisted at P6. Cortical DTI eigenvector maps reveal microstructural disruption of the radial organization corresponding to regions of neuronal death, radial glial disruption, and astrocytosis. Thus, the combined use of in vivo DTI and histopathology can assist in delineating normal developmental changes and postinjury modifications in the immature rodent brain.

Key Words: brain development • cortex • diffusion tensor imaging • hypoxia–ischemia • rat


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