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The objective of this study was to evaluate changes in the substantia nigra using single\u2010 and bi\u2010tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study cohort (n = 425) included 107 healthy controls and 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers. Bi\u2010tensor free water, free\u2010water\u2010corrected fractional anisotropy, free\u2010water\u2010corrected mean diffusivity, single\u2010tensor fractional anisotropy, and single\u2010tensor mean diffusivity were computed for the anterior and posterior substantia nigra. Correlations were computed between diffusion MRI measures and clinical measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the posterior substantia nigra, free water was greater for PSP than MSA and PD patients and controls. PD and MSA both had greater free water than controls. Free\u2010water\u2010corrected fractional anisotropy values were greater for PSP patents than for controls and PD patients. PSP and MSA patient single\u2010tensor mean diffusivity values were greater than controls, and single\u2010tensor fractional anisotropy values were lower for PSP patients than for healthy controls. The parkinsonism effect size for free water was 0.145 in the posterior substantia nigra and 0.072 for single\u2010tensor mean diffusivity. The direction of correlations between single\u2010tensor mean diffusivity and free\u2010water values and clinical scores was similar at each site.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Free\u2010water values in the posterior substantia nigra provide a consistent pattern of findings across patients with PD, MSA, and PSP in a large cohort across 3 sites. Free water in the posterior substantia nigra relates to clinical measures of motor and cognitive symptoms in a large cohort of parkinsonism. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27100","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T06:26:41Z","timestamp":1500272801000},"page":"1457-1464","source":"Crossref","is-referenced-by-count":97,"title":["Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study"],"prefix":"10.1002","volume":"32","author":[{"given":"Edward","family":"Ofori","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-5073","authenticated-orcid":false,"given":"Florian","family":"Krismer","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Medical University Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana G.","family":"Burciu","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Radiology Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna L.","family":"McCracken","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mechelle M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology Penn State \u2013 Milton S. 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