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    Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study

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    Author
    Cardenas, A.M.
    Sarlls, J.E.
    Kwan, J.Y.
    Date
    2017
    Journal
    NeuroImage: Clinical
    Publisher
    Elsevier Inc.
    Type
    Article
    
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    See at
    https://www.doi.org/10.1016/j.nicl.2017.04.024
    Abstract
    Objectives The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. Methods Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters. Results The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with C9orf72 mutations, and increased reactive astrocytes throughout the callosum. Conclusion Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role. Copyright 2017
    Sponsors
    This study was supported by the intramural program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (ZO1 NS002976).
    Keyword
    7 T MRI
    Amyotrophic lateral sclerosis
    Microglia
    Motor neuron disease
    Pathology
    Steady-state free precession
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019030136&doi=10.1016%2fj.nicl.2017.04.024&partnerID=40&md5=afe6a5781d729b655215dbc2439cc38c; http://hdl.handle.net/10713/9879
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.nicl.2017.04.024
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