{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:28:31Z","timestamp":1791941311860,"version":"4.3.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["SI-2301-40767"],"award-info":[{"award-number":["SI-2301-40767"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis Journal \u2013 Experimental, Translational and Clinical"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>SPRINT-MS was a placebo-controlled phase 2 trial of ibudilast in secondary and primary progressive multiple sclerosis. The trial included multimodal imaging to assess brain tissue integrity. This contribution focuses on improved analysis methods of diffusion tensor imaging to refine its application in clinical trials.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>Reassess diffusion tensor imaging from the SPRINT-MS trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Postprocessing incorporated corrections for bulk motion, eddy current distortion, outlier replacement, and intra-volume movement. The ICBM-DTI-81 white matter parcellation map was coregistered into native space. Six unilateral and 21 bilateral regions of interest were identified. Median radial diffusivity was the primary outcome measure for this analysis. A linear mixed-effects model was used to assess the interaction between time and treatment for the outcome measure with Holm correction for multiple comparisons.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              Radial diffusivity in the cingulum and cerebellar peduncles showed a significant difference in rate of change between treatment and placebo groups (2.7\u20137.4 \u00d7 10\n              <jats:sup>\u22123<\/jats:sup>\n              mm\n              <jats:sup>2<\/jats:sup>\n              \/s per 24-week time period,\n              <jats:italic>p<\/jats:italic>\n              \u2009&lt;\u20090.04). Radial diffusivity was unchanged (declined) in the treatment (placebo) groups, consistent with preservation (deterioration) of tissue integrity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our results suggest that the diffusion tensor imaging of the cingulum and cerebellar peduncles may be useful target outcome metrics in neuroprotective trials in progressive multiple sclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1177\/20552173251361225","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T12:15:11Z","timestamp":1756210511000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Diffusion tensor imaging in the SPRINT-MS clinical trial: Advancing trial methodology"],"prefix":"10.1177","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-4494","authenticated-orcid":false,"given":"Ken","family":"Sakaie","sequence":"first","affiliation":[{"name":"Diagnostics Institute Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6283-1990","authenticated-orcid":false,"given":"Mengke","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1891-7477","authenticated-orcid":false,"given":"Nancy","family":"Obuchowski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-8436","authenticated-orcid":false,"given":"Mark J","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-6035","authenticated-orcid":false,"given":"Jian","family":"Lin","sequence":"additional","affiliation":[{"name":"Diagnostics Institute Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-3717","authenticated-orcid":false,"given":"Robert J","family":"Fox","sequence":"additional","affiliation":[{"name":"Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803583"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011314"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585231224702"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207551"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910360612"},{"key":"e_1_3_5_7_2","volume-title":"TORTOISE: an integrated software package for processing of diffusion MRI dataISMRM 18th Annual Meeting","author":"Pierpaoli C","unstructured":"Pierpaoli C, Walker L, Irfanoglu M, et al. 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