{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:15:36Z","timestamp":1787724936940,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Studies have demonstrated the potential of muscle MRIs to measure disease progression in ALS. However, the responsiveness and utility of quantitative muscle MRIs in an ALS clinical trial remain unknown. This study aimed to determine the responsiveness of quantitative muscle MRIs to measure disease progression in ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Longitudinal quantitative muscle MRIs were obtained in an ALS study that delivered human neural progenitor cells to the spinal cord (NCT02943850). Participants underwent MRIs at baseline, 1, 3, 6, 9, and 12\u2009months. MRI measures included fat fraction (ff), water <jats:italic>T<\/jats:italic>2 (<jats:italic>T<\/jats:italic>\n<jats:sub>2m<\/jats:sub>), cross\u2010sectional area (CSA), and remaining muscle area (RMA). Non\u2010MRI measures included strength via Accurate Test of Limb Isometric Strength (ATLIS) and the ALSFRS\u2010R. Standardized response means (SRM) were calculated at 1, 3, 6, and 12\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant increases in muscle FF and decreases in CSA and RMA were seen as early as 1\u2009month from baseline. At 6\u2009months, the most responsive measures were muscle FF (SRM<jats:sub>thigh<\/jats:sub>\u2009=\u20091.85, SRM<jats:sub>calf<\/jats:sub>\u2009=\u20091.39), <jats:italic>T<\/jats:italic>\n<jats:sub>2m<\/jats:sub> (SRM<jats:sub>thigh<\/jats:sub>\u2009=\u20091.2, SRM<jats:sub>calf<\/jats:sub>\u2009=\u20091.71), CSA (SRM<jats:sub>thigh<\/jats:sub>\u2009=\u2009\u22121.58, SRM<jats:sub>calf<\/jats:sub>\u2009=\u2009\u22121.14), RMA (SRM<jats:sub>thigh<\/jats:sub>\u2009=\u2009\u22121.77, SRM<jats:sub>calf<\/jats:sub>\u2009=\u2009\u22121.28), and strength tested via ATLIS (SRM<jats:sub>knee extension<\/jats:sub>\u2009=\u2009\u22121.79, SRM<jats:sub>knee flexion<\/jats:sub>\u2009=\u2009\u22121.3). The ALSFRS\u2010R was the least responsive at 6\u2009months (SRM\u2009=\u2009\u22120.85). Muscle FF and <jats:italic>T<\/jats:italic>\n<jats:sub>2m<\/jats:sub> correlated with ALSFRS\u2010R leg subscores and MRI measures demonstrated varying degrees of correlation with strength.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>High responsiveness and low variability make quantitative muscle MRI a novel and complementary outcome measure for ALS clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28306","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T10:39:06Z","timestamp":1732876746000},"page":"171-182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Longitudinal Quantitative <scp>MRI<\/scp> Provides Responsive Outcome Measures for Early and Late Muscle Changes in <scp>ALS<\/scp>"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-1852","authenticated-orcid":false,"given":"Frank","family":"Diaz","sequence":"first","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute Cedars\u2010Siniai Medical Center  Los Angeles California USA"},{"name":"Department of Neurology Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Thornton","sequence":"additional","affiliation":[{"name":"Neuroradiological Academic Unit UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.","family":"Wastling","sequence":"additional","affiliation":[{"name":"Neuroradiological Academic Unit UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer","family":"Asaab","sequence":"additional","affiliation":[{"name":"Neuroradiological Academic Unit UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper M.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Queen Square Centre for Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Zafeiropoulos","sequence":"additional","affiliation":[{"name":"Neuroradiological Academic Unit UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bresee","sequence":"additional","affiliation":[{"name":"Biostatistics Shared Resources Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Allred","sequence":"additional","affiliation":[{"name":"Department of Neurology Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Novartis Institutes for Biomedical Research  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Avalos","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute Cedars\u2010Siniai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-4575","authenticated-orcid":false,"given":"Richard A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Baloh","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute Cedars\u2010Siniai Medical Center  Los Angeles California USA"},{"name":"Department of Neurology Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Novartis Institutes for Biomedical Research  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive N.","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Board of Governors Regenerative Medicine Institute Cedars\u2010Siniai Medical Center  Los Angeles California 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