title: Free-water imaging in Parkinson's disease and atypical parkinsonism.
abstract: Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease group comparisons, the support vector machine 10-fold cross-validation area under the curve was between 0.93-1.00 and there was high sensitivity and specificity. The regions and diffusion measures selected by the model varied across comparisons and are consistent with pathological studies. In conclusion, the current study used a novel bi-tensor diffusion analysis model to indicate that all forms of parkinsonism had elevated free-water in the substantia nigra. Beyond the substantia nigra, both multiple system atrophy and progressive supranuclear palsy, but not Parkinson's disease, showed a broad network of elevated free-water and altered free-water corrected fractional anisotropy that included the basal ganglia, thalamus, and cerebellum. These findings may be helpful in the differential diagnosis of parkinsonian disorders, and thereby facilitate the development and assessment of targeted therapies.
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Planetta
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Ofori
authors.affiliation: 2 Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Roxana G
authors.initials: RG
authors.lastname: Burciu
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Priyank
authors.initials: P
authors.lastname: Shukla
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: DeSimone
authors.affiliation: 3 Center for Movement Disorders and Neurorestoration, University of Florida, USA 4 Department of Neurology, University of Florida, USA 5 Department of Neurosurgery, University of Florida, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: 3 Center for Movement Disorders and Neurorestoration, University of Florida, USA 4 Department of Neurology, University of Florida, USA.
authors.forename: Nikolaus R
authors.initials: NR
authors.lastname: McFarland
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA 4 Department of Neurology, University of Florida, USA 6 Department of Biomedical Engineering, University of Florida, USA vcourt@ufl.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Vaillancourt
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000378:metabolism; D014867:Water / Q000378:metabolism*
chemical_list: D014867:Water
keywords: Parkinson’s disease; diffusion MRI; extracellular space; multiple system atrophy; progressive supranuclear palsy