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High-resolution diffusion tensor imaging of fixed brain in a mouse model of Pelizaeus–Merzbacher disease: comparison with quantitative measures of white matter pathology

Authors

  • Torsten Ruest,

    1. Institute of Neuroscience and Psychology and Glasgow Experimental Magnetic Resonance Imaging Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • William M. Holmes,

    1. Institute of Neuroscience and Psychology and Glasgow Experimental Magnetic Resonance Imaging Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • Jennifer A. Barrie,

    1. Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • Ian R. Griffiths,

    1. Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • Thomas J. Anderson,

    1. Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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  • Deborah Dewar,

    Corresponding author
    1. Institute of Neuroscience and Psychology and Glasgow Experimental Magnetic Resonance Imaging Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
    • Wellcome Surgical Institute, Garscube Estate, University of Glasgow, Glasgow, G61 1QH, UK.

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  • Julia M. Edgar

    1. Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
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Abstract

Diffusion tensor imaging (DTI) is a powerful technique for the noninvasive assessment of the central nervous system. To facilitate the application of this technique to in vivo studies, we characterised a mouse model of the leukodystrophy, Pelizaeus–Merzbacher disease (PMD), comparing high-resolution ex vivo DTI findings with quantitative histological analysis of selected areas of the brain. The mice used in this study (Plp1-transgenic) carry transgenic copies of the Plp1 gene and are models for PMD as a result of gene duplication. Plp1 transgenic mice display a mild ataxia and experience frequent seizures around the time at which they were imaged. Axial (λ1) and radial (RD) diffusivities and fractional anisotropy (FA) data were analysed using an exploratory whole-brain voxel-based method, a voxel-based approach using tract-based spatial statistics (TBSS), and by application of conventional region of interest (ROI) analyses to selected white matter tracts. Raw t value maps and TBSS analyses indicated widespread changes throughout the brain of Plp1-transgenic mice compared with the wild-type. ROI analyses of the corpus callosum, anterior commissure and hippocampal fimbria showed that FA was reduced significantly, whereas λ1 and RD were increased significantly, in Plp1-transgenic mice compared with the wild-type. The DTI data derived from ROI analyses were subsequently compared with histological measures taken in the same regions. These revealed an almost complete absence of myelin, preservation of axons, marked astrocytosis and increased or unchanged cell densities. These data contribute to our growing understanding of the basis of anisotropic water diffusion in the normal and diseased nervous system. Copyright © 2011 John Wiley & Sons, Ltd.

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