{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:18:51Z","timestamp":1786976331882,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K24AG064114"],"award-info":[{"award-number":["K24AG064114"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS097783"],"award-info":[{"award-number":["R01NS097783"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS122419"],"award-info":[{"award-number":["U01NS122419"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Reliable biomarkers are essential for tracking disease progression and advancing treatments for multiple system atrophy (MSA). In this study, we propose the MSA Atrophy Index (MSA\u2010AI), a novel composite volumetric measure to distinguish MSA from related disorders and monitor disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen participants with an initial diagnosis of probable MSA were enrolled in the longitudinal bioMUSE study and underwent 3T MRI, biofluid analysis, and clinical assessments at baseline, 6, and 12\u2009months. Final diagnoses were determined after 12\u2009months using clinical progression, imaging, and fluid biomarkers. Ten participants retained an MSA diagnosis, while five were reclassified as either Parkinson disease (PD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) or dementia with Lewy bodies (DLB,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091). Cross\u2010sectional comparisons included additional MSA cases (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926), healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923), pure autonomic failure (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923), PD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200956), and DLB (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098). Lentiform nucleus, cerebellum, and brainstem volumes were extracted using deep learning\u2010based segmentation. Z\u2010scores were computed using a normative dataset (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009469) and integrated into the MSA\u2010AI. Group differences were tested with linear regression; longitudinal changes and clinical correlations were assessed using mixed\u2010effects models and Spearman correlations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MSA patients exhibited significantly lower MSA\u2010AI scores compared to all other diagnostic groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The MSA\u2010AI effectively distinguished MSA from related synucleinopathies, correlated with baseline clinical severity (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u22120.57,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and predicted disease progression (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u22120.55,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). Longitudinal reductions in MSA\u2010AI were associated with worsening clinical scores over 12\u2009months (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u22120.61,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The MSA\u2010AI is a promising imaging biomarker for diagnosis and monitoring disease progression in MSA. These findings require validation in larger, independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70106","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T05:09:22Z","timestamp":1752556162000},"page":"1823-1833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The\n                    <scp>MSA<\/scp>\n                    Atrophy Index (\n                    <scp>MSA<\/scp>\n                    \u2010\n                    <scp>AI<\/scp>\n                    ): An Imaging Marker for Diagnosis and Clinical Progression in Multiple System Atrophy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-7071","authenticated-orcid":false,"given":"Paula","family":"Trujillo","sequence":"first","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-4247","authenticated-orcid":false,"given":"Kilian","family":"Hett","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Iregui","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manus J.","family":"Donahue","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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