{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:18:13Z","timestamp":1773047893210,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuroimaging"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Structural MRI (sMRI) is used in monitoring multiple sclerosis (MS) but lacks sensitivity in detecting clinically relevant damage to normal\u2010appearing white matter (NAWM), that is, pre\u2010lesional tissue, and specificity for identifying the underlying substrate of injury. In this longitudinal study, we identified pre\u2010lesional tissue in MS patients and investigated its microstructure by modeling diffusion\u2010weighted imaging (DWI) data using diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 18 patients with relapsing\u2010remitting MS (10 females, 31.92\u00a0\u00b1\u00a08.09\u00a0years, disease duration 0.91\u00a0\u00b1\u00a01.81\u00a0years) and 18 healthy controls (10 females, 31.89\u00a0\u00b1\u00a08.15\u00a0years). Participants underwent two sMRI and DWI sessions (baseline and follow\u2010up) with the same protocols. Average apparent diffusion coefficient (ADC), fractional anisotropy (FA), orientation dispersion index (ODI), and neurite density index (NDI) were estimated in data\u2010driven regions of interest: nonpersistent lesional tissue (lesional tissue at baseline, resolved at follow\u2010up), lesions that only existed at follow\u2010up (pre\u2010lesional tissue at baseline, lesions at follow\u2010up), persistent lesional tissue (lesions at baseline and follow\u2010up), and NAWM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to NAWM, pre\u2010lesional tissue showed lower ODI, and resolved lesional tissue showed higher FA and ADC and lower ODI and NDI. Over time, persistent lesional tissue showed a decrease in FA and ODI and an increase in NDI. Compared to nonpersistent lesional tissue, persistent lesional tissue showed higher ADC and lower NDI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DWI and, more particularly, NODDI, can reveal the unique microstructure of persistent, resolved, and pre\u2010lesional tissue in MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jon.70022","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T09:34:56Z","timestamp":1739352896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Identification of Pre\u2010Lesional Tissue in Multiple Sclerosis With Advanced Diffusion MRI"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1448-1859","authenticated-orcid":false,"given":"Maria","family":"Caranova","sequence":"first","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra  Coimbra Portugal"}]},{"given":"J\u00falia F.","family":"Soares","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra  Coimbra Portugal"}]},{"given":"Daniela Jardim","family":"Pereira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra  Coimbra Portugal"},{"name":"Neuroradiology Functional Unit, Imaging Service, Coimbra Local Health Unit  Coimbra Portugal"},{"name":"Faculty of Medicine, University of Coimbra  Coimbra Portugal"}]},{"given":"Ana Cl\u00e1udia","family":"Lima","sequence":"additional","affiliation":[{"name":"Neurology Department Coimbra Hospital and University Centre  Coimbra Portugal"}]},{"given":"L\u00edvia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra  Coimbra Portugal"},{"name":"Neurology Department Coimbra Hospital and University Centre  Coimbra Portugal"}]},{"given":"S\u00f3nia","family":"Batista","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra  Coimbra Portugal"},{"name":"Neurology Department Coimbra Hospital and University Centre  Coimbra Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-6373","authenticated-orcid":false,"given":"Miguel","family":"Castelo\u2010Branco","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra  Coimbra Portugal"},{"name":"Faculty of Medicine, University of Coimbra  Coimbra Portugal"}]},{"given":"Jo\u00e3o V.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra  Coimbra Portugal"},{"name":"Champalimaud Research, Champalimaud Foundation  Lisbon Portugal"}]}],"member":"311","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"issue":"3","key":"e_1_2_7_2_1","first-page":"175","article-title":"Multiple Sclerosis Review","volume":"37","author":"Goldenberg M. 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