@article{d23907ba29794662a7e3a154506c9a8c,
title = "Increased free water in the substantia nigra of Parkinson's disease: A single-site and multi-site study",
abstract = "Measures from diffusion magnetic resonance imaging reflect changes in the substantia nigra of Parkinson's disease. It is the case, however, that partial volume effects from free water can bias diffusion measurements. The bi-tensor diffusion model was introduced to quantify the contribution of free water and eliminates its bias on estimations of tissue microstructure. Here, we test the hypothesis that free water is elevated in the substantia nigra for Parkinson's disease compared with control subjects. This hypothesis was tested between large cohorts of Parkinson's disease and control participants in a single-site study and validated against a multisite study using multiple scanners. The fractional volume of free water was increased in the posterior region of the substantia nigra in Parkinson's disease compared with control subjects in both the single-site and multi-site studies. We did not observe changes in either cohort for free-water-corrected fractional anisotropy or free-water-corrected mean diffusivity. Our findings provide new evidence that the free-water index reflects alteration of the substantia nigra in Parkinson's disease, and this was evidenced across both single-site and multi-site cohorts.",
keywords = "Diffusion MRI, Free-water mapping, Parkinson's disease, Substantia nigra",
author = "Edward Ofori and Ofer Pasternak and Planetta, {Peggy J.} and Roxana Burciu and Amy Snyder and Marcelo Febo and Golde, {Todd E.} and Okun, {Michael S.} and Vaillancourt, {David E.}",
note = "Funding Information: Dr Pasternak receives grant support from National Institutes of Health (R01 MH074794, P41 EB015902, R01 AG042512, U01 NS083223, R01 MH102377) , Department of Defense (W81XWH-08-2-0159) , and the Brain and Behavior Research Foundation , and consults for projects at Florida University and the Laureate Institute for Brain Research. Dr Golde receives grant support from National Institutes of Health (R01 AG018454, U01 AG046139, P01 CA1660009) , Michael J. Fox Foundation for Parkinson's Research , Ellison Medical Foundation , and Thome Foundation . Dr Okun serves as a consultant for the National Parkinson Foundation and has received research grants from National Institutes of Health (R01 NS052318, R01 NS075012) , National Parkinson Foundation , the Michael J. Fox Foundation for Parkinson's Research , the Parkinson Alliance , Smallwood Foundation , the Bachmann-Strauss Dystonia and Parkinson Foundation , the Tourette Syndrome Association , and the UF Foundation . He has previously received honoraria but in the past >48 months has received no support from industry. He has received royalties for publications with Demos, Manson, Amazon, Smashwords, and Cambridge (movement disorders books). He is an associate editor for New England Journal of Medicine Journal Watch Neurology. He participated in Continuing Medical Education activities on movement disorders (in the last 36) months sponsored by PeerView, Prime, and Vanderbilt University. The institution and not Dr Okun receives grants from Medtronic and ANS / St. Jude , and the principal investigator has no financial interest in these grants. He has participated as a site principal investigator and/or co-investigator for several National Institutes of Health, foundation, and industry sponsored trials over the years but has not received honoraria. Dr Vaillancourt receives grant support from National Institutes of Health (R01 NS052318, R01 NS075012) , Michael J. Fox Foundation for Parkinson's Research , Bachmann-Strauss Dystonia and Parkinson Foundation , Tyler{\textquoteright}s Hope Foundation , and consults for projects at UT Southwestern Medical Center, University of Illinois at Chicago, and Great Lakes NeuroTechnologies. He is co-founder of Neuroimaging Solutions, LLC. The remaining authors report no disclosures. Funding Information: Data used in the preparation of this article were obtained from the PPMI database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . This work was supported by the National Institutes of Health ( R01 NS052318 , R01 NS075012 ) and the Bachmann-Strauss Dystonia and Parkinson Foundation . Funding for PPMI was provided by the Michael J. Fox Foundation for Parkinson's Research . Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = feb,
day = "1",
doi = "10.1016/j.neurobiolaging.2014.10.029",
language = "English (US)",
volume = "36",
pages = "1097--1104",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "2",
}