{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:42:17Z","timestamp":1788838937947,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","award":["22\/R-Multi\/028"],"award-info":[{"award-number":["22\/R-Multi\/028"]}],"id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["NMSS 4281-RG-A1"],"award-info":[{"award-number":["NMSS 4281-RG-A1"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["NMSS RG 4729A2\/1"],"award-info":[{"award-number":["NMSS RG 4729A2\/1"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["NMSS RG 1802-30468"],"award-info":[{"award-number":["NMSS RG 1802-30468"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS078322-01-A1"],"award-info":[{"award-number":["R01NS078322-01-A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006751","name":"United States Army","doi-asserted-by":"publisher","award":["W81XWH-13-1-0122"],"award-info":[{"award-number":["W81XWH-13-1-0122"]}],"id":[{"id":"10.13039\/100006751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In multiple sclerosis, different types of lesions and their localization can have varying effects on clinical disability and disease progression. Ultra-high field 7-Tesla MRI improves the visualization of cortical, especially subpial, lesions and of white matter lesions with a paramagnetic rim that are associated with smoldering inflammation. Spinal cord atrophy is also a critical determinant of clinical disability in multiple sclerosis, but its importance relative to paramagnetic rim and cortical lesions in predicting neurological disability and its progression remains unclear. In this longitudinal study, we aimed to identify the most relevant predictors of both the baseline Expanded Disability Status Scale status and 4-year progression independent of relapse activity in a heterogeneous multiple sclerosis cohort. One-hundred-twelve patients (83 relapsing-remitting and 29 secondary progressive; mean age 42.3 years, mean disease duration 9.8 years) underwent 7-Tesla T2* susceptibility-weighted images to segment paramagnetic rim lesions, non-rim white matter lesions and cortical lesions; 3-Tesla T1-weighted brain MRI images extended to the C2-C3 spinal cord were employed to obtain brain volumes and the spinal cord C2-C3 cross-sectional area using FreeSurfer and Spinal Cord Toolbox. Clinical disability was assessed through the Expanded Disability Status Scale at baseline and, in 97\/112 patients (86.6%), after a mean follow-up of 4.0 years. The association between imaging metrics and clinical outcome was evaluated using correlations and regression models, corrected for age, sex, treatment class and clinical follow-up time. The main predictors of baseline Expanded Disability Status Scale were cortical lesion (\u03b2 = 2.9 \u00d7 10\u22124, P = 0.001), non-rim white matter lesion (\u03b2 = 1.2 \u00d7 10\u22124, P &amp;lt; 0.001) volumes, brain white matter volume (\u03b2 = \u221215.68, P = 0.017) and C2-C3 cross-sectional area (\u03b2 = \u22120.68, P = 0.003). At follow-up, 23\/97 patients (24%) experienced progression independent of relapse activity. Progression independent of relapse activity was associated with paramagnetic rim lesion volume (odds ratio = 1.0006 per mm\u00b3 increase, P = 0.030), cortical lesion volume (odds ratio = 1.0005 per mm\u00b3 increase, P = 0.011) and brain white matter volume (odds ratio = 0.97 \u00d7 10\u221220, P &amp;lt; 0.001). However, a stepwise logistic regression model assessing clinical, lesion and atrophy variables identified cortical lesion volume as the strongest independent predictor of progression independent of relapse activity (odds ratio = 1.0006 per mm\u00b3 increase, P = 0.005). In multiple sclerosis, different imaging biomarkers contribute differently to current disability and progression independent of relapse activity. Spinal cord atrophy mainly explains the current Expanded Disability Status Scale, while brain white matter atrophy and paramagnetic rim lesions provide additional insights into future disability trajectory. Among all markers, cortical lesions emerged as the main driver for progression independent of relapse activity.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag059","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:35:49Z","timestamp":1771936549000},"source":"Crossref","is-referenced-by-count":1,"title":["Spinal cord versus brain imaging biomarkers of multiple sclerosis trajectory combining 7T and 3T MRI"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-6246","authenticated-orcid":false,"given":"Alessandro","family":"Miscioscia","sequence":"first","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata , Rome 00133 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-207X","authenticated-orcid":false,"given":"Constantina A","family":"Treaba","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Barbuti","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Department of Human Neuroscience, Sapienza University , Rome 00185 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-9406","authenticated-orcid":false,"given":"Valeria T","family":"Barletta","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A","family":"Sloane","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-2633","authenticated-orcid":false,"given":"Eric C","family":"Klawiter","sequence":"additional","affiliation":[{"name":"A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Department of Neurology, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Cohen-Adad","sequence":"additional","affiliation":[{"name":"NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal , Montreal, QC H3T 1N8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Padua , Padua 35128 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pantano","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, Sapienza University , Rome 00185 ,","place":["Italy"]},{"name":"IRCCS Neuromed , Pozzilli (IS) 86077 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Mainero","sequence":"additional","affiliation":[{"name":"A. 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Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"issue":"2","key":"2026041703573821100_fcag059-B1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N Engl J Med"},{"issue":"9","key":"2026041703573821100_fcag059-B2","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire 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