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We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5\u00a0years, n\u2009=\u200967); MS2 (5\u201315\u00a0years, n\u2009=\u2009107); and MS3 (more than15 years, n\u2009=\u200973). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.<\/jats:p>","DOI":"10.1038\/s41598-021-96132-x","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T06:30:05Z","timestamp":1629354605000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients"],"prefix":"10.1038","volume":"11","author":[{"given":"Elisabeth","family":"Solana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloy","family":"Martinez-Heras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Montal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Vilaplana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Lopez-Soley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Radua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Sola-Valls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Montejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Pulido-Valdeolivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sep\u00falveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magi","family":"Andorra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Berenguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Villoslada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. H.","family":"Martinez-Lapiscina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Saiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Llufriu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"96132_CR1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/S1474-4422(14)70250-9","volume":"14","author":"MA Rocca","year":"2015","unstructured":"Rocca, M. A. et al. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol. 14, 302\u2013317 (2015).","journal-title":"Lancet Neurol."},{"key":"96132_CR2","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1002\/hbm.23993","volume":"39","author":"G Mangeat","year":"2018","unstructured":"Mangeat, G. et al. Changes in structural network are associated with cortical demyelination in early multiple sclerosis. Hum. Brain Mapp. 39, 2133\u20132146 (2018).","journal-title":"Hum. Brain Mapp."},{"key":"96132_CR3","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nrn3900","volume":"16","author":"M Calabrese","year":"2015","unstructured":"Calabrese, M. et al. Exploring the origins of grey matter damage in multiple sclerosis. Nat. Rev. Neurosci. 16, 147\u2013158 (2015).","journal-title":"Nat. Rev. Neurosci."},{"key":"96132_CR4","doi-asserted-by":"publisher","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","volume":"8","author":"H Lassmann","year":"2018","unstructured":"Lassmann, H. Multiple sclerosis pathology. 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E.S and E.L.-S received travel reimbursement from Sanofi; N.S.-V. received compensation for consulting services and speaker honoraria from Genzyme-Sanofi, Novartis, Roche and Almirall; Y.B. received speaking honoraria from Biogen, Novartis and Genzyme; I.P.-V. received travel reimbursement from Roche and Genzyme, and she holds stock options in Aura Innovative Robotics. Currently, she is an employee at UCB Pharma, her contribution to this work is associated with her previous work at IDIBAPS; M.S. received speaker honoraria from Genzyme, Novartis and Biogen; M.A. holds equity shares of Bionure, S.L. and Goodgut S.L. and stock options of Attune Neurosciences Inc. He is currently an employee of Roche, although his contribution to this work is associated with his previous work at IDIBAPS; E.H.M.-L. received travel support for international and national meetings from Roche and Sanofi-Genzyme, and honoraria for consultancies from Novartis, Roche and Sanofi. She is currently employed by the European Medicines Agency (Human Medicines) since 16 April 2019. This article is related with her activity under Hospital Clinic of Barcelona\/IDIBAPS affiliation and consequently, as external activity, it does not represent the views of the Agency or its Committees. She is a member of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium; A.S. received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA, Novartis and Roche; J.F. has received compensation for consultancies to Novartis, L\u00fcndbeck and AC Immune; S.L. received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, TEVA, Genzyme, Sanofi and Merck.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16805"}}