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      Free-Water Improves Detection of Changes in the Substantia Nigra in Parkinsonism: A Multi-Site Study

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          Abstract

          Background

          Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials.

          Objective

          To evaluate changes in the substantia nigra using single- and bi-tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP.

          Methods

          The study cohort (N=425) included 107 healthy controls, 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers. Bi-tensor free-water, free-water corrected fractional anisotropy, free-water corrected mean diffusivity, single-tensor fractional anisotropy and single-tensor mean diffusivity were computed for anterior and posterior substantia nigra. Correlations were computed between diffusion MRI measures and clinical measures.

          Results

          In the posterior substantia nigra, free-water was greater for PSP than MSA, PD, and controls. PD and MSA both had greater free-water than controls. Free-water corrected fractional anisotropy values were greater for PSP when compared to controls and PD. PSP and MSA single-tensor mean diffusivity values were greater than controls and single-tensor fractional anisotropy values were lower for PSP than healthy controls. The parkinsonism effect size for free-water in the posterior substantia nigra was 0.145 and for single-tensor mean diffusivity was 0.072. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores were similar at each site.

          Conclusions

          Free-water values in the posterior substantia nigra provide consistent pattern of findings across PD, MSA and PSP in a large cohort across three sites. Free-water in the posterior substantia nigra relates to clinical measures of motor and cognitive symptoms in a large cohort of parkinsonism.

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          Author and article information

          Journal
          8610688
          5937
          Mov Disord
          Mov. Disord.
          Movement disorders : official journal of the Movement Disorder Society
          0885-3185
          1531-8257
          30 November 2017
          17 July 2017
          October 2017
          06 December 2017
          : 32
          : 10
          : 1457-1464
          Affiliations
          [1 ]Department of Applied Physiology and Kinesiology, University of Florida, USA
          [2 ]Departments of Psychiatry and Radiology, Brigham and Women’s Hospital, Harvard Medical School, USA
          [3 ]Department of Neurology, Penn State-Milton S. Hershey Medical Center, Hershey, PA
          [4 ]Department of Pharmacology, Penn State-Milton S. Hershey Medical Center, Hershey, PA
          [5 ]Departments of Neurosurgery, Radiology, and Kinesiology, Penn State-Milton S. Hershey Medical Center, Hershey, PA
          [6 ]Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
          [7 ]Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria
          [8 ]Center for Movement Disorders and Neurorestoration, University of Florida, USA
          [9 ]Department of Neurology, University of Florida, USA
          [10 ]Department of Neurosurgery, University of Florida, USA
          [11 ]Department of Biomedical Engineering, University of Florida, USA
          [12 ]Department of Neuroradiology, Medical University Innsbruck
          [13 ]Department of Public Health Sciences, Medical College of South Carolina
          Author notes
          Corresponding Author: David E. Vaillancourt, PhD, Department of Applied Physiology and Kinesiology, University of Florida, PO Box 118205, Gainesville, FL 32611-8205, vcourt@ 123456ufl.edu , Phone: 352-294-1770, Fax: 352-392-5262
          Article
          PMC5718046 PMC5718046 5718046 nihpa923584
          10.1002/mds.27100
          5718046
          28714593
          8e658cb4-28b4-41e6-8ff6-803798eb382a
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