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We first examined WM microstructure using diffusion\u2010weighted imaging and then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light, a biofluid marker of axonal degeneration\u2014in parallel with the mutant huntingtin protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined WM change in HD gene carriers from the HD\u2013CSFcohort, baseline visit. We used standard\u2010diffusion magnetic resonance imaging to measure metrics including fractional anisotropy, a marker of WM integrity, and diffusivity; a novel diffusion model (neurite orientation dispersion and density imaging) to measure axonal density and organization; T1\u2010weighted and T2\u2010weighted structural magnetic resonance imaging images to derive proxy iron content and myelin\u2010contrast measures; and biofluid concentrations of neurofilament light (in cerebrospinal fluid (CSF) and plasma) and mutant huntingtin protein (in CSF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HD gene carriers displayed reduced fractional anisotropy and increased diffusivity when compared with controls, both of which were also associated with disease progression, CSF, and mutant huntingtin protein levels. HD gene carriers also displayed proxy measures of reduced myelin contrast and iron in the striatum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, these findings present a more complete characterization of HD\u2010related microstructural brain changes. The correlation between reduced fractional anisotropy, increased axonal orientation, and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, whereas higher quantitative T2 signal and lower myelin\u2010contrast may indicate a process of demyelination limited to the striatum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.12866","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T13:53:27Z","timestamp":1573480407000},"page":"52-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Characterizing White Matter in Huntington's Disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Sarah","family":"Gregory","sequence":"first","affiliation":[{"name":"University College London Huntington's Disease Centre, Department of Neurodegenerative Disease University College London Queen Square Institute of Neurology, University College London  London 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