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Widespread white matter damage affects the brain of patients with HD at very early stages of the disease. Fixel-based analysis (FBA) is a novel method to investigate the contribution of individual crossing fibers to the white matter damage and to detect possible alterations in both fiber density and fiber-bundle morphology. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS), on the other hand, quantifies the motion of brain metabolites in vivo, thus enabling the investigation of microstructural alteration of specific cell populations. The aim of this study was to identify novel specific microstructural imaging markers of white matter degeneration in HD, by combining FBA and DW-MRS. Twenty patients at an early stage of HD and 20 healthy controls were recruited in a monocentric study. Using diffusion imaging we observed alterations to the brain microstructure and their morphology in patients with HD. Furthermore, FBA revealed specific fiber populations that were affected by the disease. Moreover, the mean diffusivity of the intra-axonal metabolite <jats:italic>N<\/jats:italic>-acetylaspartate, co-measured with <jats:italic>N<\/jats:italic>-acetylaspartylglutamate (tNAA), was significantly reduced in the corpus callosum of patients compared to controls. FBA and DW-MRS of tNAA provided more specific information about the biological mechanisms underlying HD and showed promise for early investigation of white matter degeneration in HD.<\/jats:p>","DOI":"10.1038\/s41598-021-92532-1","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T10:06:11Z","timestamp":1624442771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Multiparametric characterization of white matter alterations in early stage Huntington disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Isaac M.","family":"Adanyeguh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Branzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Delorme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"M\u00e9neret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Lorraine","family":"Monin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Luton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Durr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanoel","family":"Sabidussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Mochel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"92532_CR1","doi-asserted-by":"publisher","unstructured":"Kremer, B. et al. 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Dr Branzoli acknowledges support from the programs 'Institut des neurosciences translationnelle' ANR-10-IAIHU-06 and 'Infrastructure d\u2019avenir en Biologie Sant\u00e9' ANR-11-INBS-0006. Dr M\u00e9neret received travel grant from Abbvie. Prof Durr received research support from the French Agency for Research, Adverum, Pfizer Inc and Minoryx therapeutics. Dr Mochel received research support by grants from INSERM, the French Agency for Research, Carnot Institutes, ASL Foundation, Ultragenyx Pharmaceutical and Minoryx therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13101"}}