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Diffusion Basis Spectrum Imaging decomposes the diffusion signal into fiber, cell, and hindered ratios indexing axonal integrity, cellularity, and extracellular space, respectively. We asked how these ratios differ between early relapsing and established non\u2010relapsing disease, change with early treatment, and relate to disability, and secondarily, whether lesions form reproducible microstructural subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty\u2010seven participants underwent multi\u2010shell diffusion MRI: 11 healthy controls, 15 treatment\u2010na\u00efve relapsing, and 11 non\u2010relapsing patients. Thirteen were rescanned ~3\u2009months after starting high\u2010efficacy disease\u2010modifying therapy. Metrics were extracted from normal\u2010appearing gray and white matter and lesions (core, rim, and perilesional white matter); Gaussian mixture model clustering of per\u2010lesion fiber, cell, and hindered ratios identified lesion subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment\u2010na\u00efve relapsing patients showed reduced normal\u2010appearing white matter fiber (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and elevated hindered ratios (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02) versus controls. Lesions had lower fiber and cell ratios and higher hindered ratio than within\u2010subject normal\u2010appearing white matter (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). After treatment, lesional fiber ratio increased (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) while lesional and gray matter cell ratios declined (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02). Lesional cell ratio was higher in relapsing than non\u2010relapsing patients at the core (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) and rim (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) but not perilesionally; treatment\u2010related improvement was similar across compartments. Clustering yielded four reproducible subtypes (edematous\u2010hypocellular, moderately cellular, actively inflamed, structurally preserved); the inflamed subtype predominated in relapsing and the edematous\u2010hypocellular in non\u2010relapsing disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Diffusion basis spectrum imaging distinguishes relapsing from non\u2010relapsing disease by lesion\u2010body cellularity and detects treatment\u2010related changes in fiber and cell compartments. Reproducible, hypothesis\u2010generating lesion subtypes support its use for in\u00a0vivo lesion phenotyping.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70546","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:33:24Z","timestamp":1791876804000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diffusion Basis Spectrum Imaging of Tissue Microstructure and Early Treatment in Multiple Sclerosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-338X","authenticated-orcid":false,"given":"Apisit","family":"Kaewsanit","sequence":"first","affiliation":[{"name":"Roy and Diana Vagelos Division of Biology &amp; Biomedical Sciences, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"},{"name":"Department of Neurology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aime","family":"Luna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, McKelvey School of Engineering Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3052-5912","authenticated-orcid":false,"given":"Bradley","family":"Judge","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9607-9840","authenticated-orcid":false,"given":"Nicole","family":"Shelley","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Friedrichsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Rajamanickam","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhude","family":"Tu","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"},{"name":"Department of Obstetrics and Gynecology, School of Medicine Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie L. 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