{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:34:50Z","timestamp":1791462890530,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate which baseline clinical and imaging characteristics best predict TSPO\u2010PET\u2010measurable reduction in glial activation following treatment of multiple sclerosis (MS), to utilize this information for designing more efficient biomarker\u2010based clinical trials targeting glial activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study pooled data from 47 pwMS treated with various approved disease\u2010modifying therapies and 18 untreated pwMS with TSPO\u2010PET imaging before and after. Therapeutic response was quantified using [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195 distribution volume ratio and percentage of active voxels in seven brain regions. Variables predicting therapeutic response were identified using linear mixed\u2010effect models. Power calculation was used to estimate the required sample size for predictor\u2010enriched cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High baseline TSPO binding in the white matter (HOT\u2010PET) was identified as the best predictor for reduction in glial activation following treatment in 6 of 14 (43%) PET variables. Internal validation confirmed that treated HOT\u2010PET patients showed enhanced therapeutic response compared with non\u2010HOT\u2010PET patients in 9 of 14 (64%) PET variables. The percentage of active voxels in the white matter was the best PET variable at capturing a significant therapeutic effect, with a Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      effect size of \u22120.779 (95% confidence interval \u22121.332; \u22120.207). In this cohort, enrichment for HOT\u2010PET patients markedly reduced the sample size required to show a positive treatment effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>HOT\u2010PET patients are more likely to benefit from neuroinflammation\u2010targeting treatments compared to non\u2010HOT\u2010PET patients. Accordingly, enriching trial cohorts for individuals with greater neuroinflammatory burden could improve statistical power and reduce the required number of participants in trials targeting harmful glial activation in MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70472","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:09:57Z","timestamp":1782965397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Baseline Neuroinflammation Stratifies\n                    <scp>TSPO<\/scp>\n                    \u2010\n                    <scp>PET<\/scp>\n                    Response to Disease\u2010Modifying Therapy in Multiple Sclerosis"],"prefix":"10.1002","author":[{"given":"Marlene T.","family":"Morch","sequence":"first","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Matilainen","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia N.","family":"Baldrighi","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-5684","authenticated-orcid":false,"given":"Marjo","family":"Nylund","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-5976","authenticated-orcid":false,"given":"Maija","family":"Saraste","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Airas","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University of Turku  Turku Finland"},{"name":"InFLAMES Research Flagship University of Turku  Turku Finland"},{"name":"Neurocenter Turku University Hospital  Turku Finland"},{"name":"Turku PET Centre University of Turku, Turku University Hospital, and \u00c5bo Akademi University  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich D. 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