Edward Ofori1, Florian Krismer2, Roxana G Burciu1, Ofer Pasternak3, Johanna L McCracken1, Mechelle M Lewis4,5, Guangwei Du4, Nikolaus R McFarland6,7, Michael S Okun6,7,8, Werner Poewe2,9, Christoph Mueller2, Elke R Gizewski9,2, Michael Schocke9,2, Christian Kremser9,2, Hong Li10, Xuemei Huang4,5,11, Klaus Seppi2, David E Vaillancourt1,6,12. 1. Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA. 2. Department of Neuroradiology, Medical University Innsbruck, Innsbruck, Austria. 3. Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 4. Department of Neurology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 5. Department of Pharmacology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 6. Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida, USA. 7. Department of Neurology, University of Florida, Gainesville, Florida, USA. 8. Department of Neurosurgery, University of Florida, Gainesville, Florida, USA. 9. Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. 10. Department of Public Health Sciences, Medical College of South Carolina, Charleston, South Carolina, USA. 11. Departments of Neurosurgery, Radiology, and Kinesiology, Penn State - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 12. Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.
Abstract
BACKGROUND: Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was 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 and 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 the 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 and PD patients and controls. PD and MSA both had greater free water than controls. Free-water-corrected fractional anisotropy values were greater for PSP patents than for controls and PD patients. PSP and MSA patient single-tensor mean diffusivity values were greater than controls, and single-tensor 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-tensor mean diffusivity. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores was similar at each site. CONCLUSIONS: Free-water 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.
BACKGROUND: Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was 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 and 184 PD, 63 MSA, and 71 PSPpatients 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 the 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 and PDpatients and controls. PD and MSA both had greater free water than controls. Free-water-corrected fractional anisotropy values were greater for PSP patents than for controls and PDpatients. PSP and MSA patient single-tensor mean diffusivity values were greater than controls, and single-tensor fractional anisotropy values were lower for PSPpatients than for healthy controls. The parkinsonism effect size for free water was 0.145 in the posterior substantia nigra and 0.072 for single-tensor mean diffusivity. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores was similar at each site. CONCLUSIONS:Free-water 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.
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