{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:09:10Z","timestamp":1790780950868,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Two recent, randomized, placebo\u2010controlled phase II\/III trials (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>: NCT01110720, NCT01049399) of davunetide and tideglusib in progressive supranuclear palsy (PSP) generated prospective, 1\u2010year longitudinal datasets of high\u2010resolution T1\u2010weighted three\u2010dimensional MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to develop a quantitative MRI disease progression measurement for clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors performed a fully automated quantitative MRI analysis employing atlas\u2010based volumetry and provide sample size calculations based on data collected in 99 PSP patients assigned to placebo in these trials. Based on individual volumes of 44 brain compartments and structures at baseline and 52 weeks of follow\u2010up, means and standard deviations of annualized percentage volume changes were used to estimate standardized effect sizes and the required sample sizes per group for future 2\u2010armed, placebo\u2010controlled therapeutic trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The highest standardized effect sizes were found for midbrain, frontal lobes, and the third ventricle. Using the annualized percentage volume change of these structures to detect a 50% change in the 1\u2010year progression (80% power, significance level 5%) required lower numbers of patients per group (third ventricle, n = 32; midbrain, n = 37; frontal lobe, n = 43) than the best clinical scale (PSP rating scale total score, n = 58). A combination of volume changes in these 3 structures reduced the number of required patients to only 20 and correlated best with the progression in the clinical scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We propose the 1\u2010year change in the volumes of third ventricle, midbrain, and frontal lobe as combined imaging read\u2010out for clinical trials in PSP that require the least number of patients for detecting efficacy to reduce brain atrophy. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26973","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T06:08:56Z","timestamp":1493014136000},"page":"842-852","source":"Crossref","is-referenced-by-count":84,"title":["Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"first","affiliation":[{"name":"Department of Neurology Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"German Center for Neurodegenerative Diseases Munich Germany"},{"name":"Department of Neurology University Hospital Gie\u00dfen and Marburg Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Sch\u00f6pe","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry Epidemiology and Medical Informatics, Saarland University Campus Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1668-9925","authenticated-orcid":false,"given":"Maria","family":"Stamelou","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Gie\u00dfen and Marburg Marburg Germany"},{"name":"Second Department of Neurology Attikon University Hospital, University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kassubek","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodoro","family":"del Ser","sequence":"additional","affiliation":[{"name":"Medical Department Noscira SA Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Boxer","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Department of Neurology, University of California San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wagenpfeil","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry Epidemiology and Medical Informatics, Saarland University Campus Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010J\u00fcrgen","family":"Huppertz","sequence":"additional","affiliation":[{"name":"Swiss Epilepsy Centre Klinik Lengg Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the AL\u2010108\u2010231 Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Tauros MRI Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Movement Disorder Society\u2010Endorsed PSP Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0347-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70088-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25824"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25815"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26580"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.04.006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm032"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003305"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.10.066"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2015.12.031"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26715"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.1"},{"key":"e_1_2_9_14_1","first-page":"A326","article-title":"The Medical Advisory Board of the Society for Progressive Supranuclear Palsy. 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