{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:27:35Z","timestamp":1779895655312,"version":"3.53.1"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuroprotection"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Huntington's disease is a progressive neurodegenerative disorder. Brain atrophy, as measured by volumetric magnetic resonance imaging (MRI), is a downstream consequence of neurodegeneration, but microstructural changes within brain tissue are expected to precede this volumetric decline. The tissue microstructure can be assayed non\u2010invasively using diffusion MRI, which also allows a tractographic analysis of brain connectivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We here used ex vivo diffusion MRI (11.7\u2009T) to measure microstructural changes in different brain regions of end\u2010stage (14 weeks of age) wild type and R6\/2 mice (male and female) modeling Huntington's disease. To probe the microstructure of different brain regions, reduce partial volume effects and measure connectivity between different regions, a 100\u2009\u03bcm isotropic voxel resolution was acquired.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although fractional anisotropy\u00a0did not reveal any difference between wild\u2010type\u00a0controls and R6\/2 mice, mean, axial, and radial diffusivity\u00a0were increased in female R6\/2 mice and decreased in male R6\/2 mice. Whole brain streamlines were only reduced in male R6\/2 mice, but streamline density was increased. Region\u2010to\u2010region tractography indicated reductions in connectivity between the cortex, hippocampus, and thalamus with the striatum, as well as within the basal ganglia (striatum\u2014globus pallidus\u2014subthalamic nucleus\u2014substantia nigra\u2014thalamus).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Biological sex and left\/right hemisphere affected tractographic results, potentially reflecting different stages of disease progression. This proof\u2010of\u2010principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions. In a translation setting, these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models, as well as patients with Huntington's disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nep3.14","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T08:21:30Z","timestamp":1671524490000},"page":"5-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ex vivo 100 \u03bcm isotropic diffusion MRI\u2010based tractography of connectivity changes in the end\u2010stage R6\/2 mouse model of Huntington's disease"],"prefix":"10.1002","volume":"1","author":[{"given":"Ashwinee","family":"Manivannan","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley M.","family":"Foley","sequence":"additional","affiliation":[{"name":"Animal Imaging Center University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Kevin","family":"Hitchens","sequence":"additional","affiliation":[{"name":"Animal Imaging Center University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Department of Neurobiology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rattray","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, Huntington's Disease Centre and UK Dementia Research Institute at UCL University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian P.","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, Huntington's Disease Centre and UK Dementia Research Institute at UCL University College London London 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