Abstract Details

Title Understanding the Effects of Free-Water Corrected diffusion MRI in Parkinson’s disease with Freezing of Gait

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 3-005

Objective To compare free-water (f_iso)-corrected and non f_iso-corrected diffusion MRI (dMRI) metrics in the white matter (WM) between Parkinson’s disease (PD) patients with freezing of gait (FOG) and without FOG (PD-nFOG).

Background f_iso fraction estimated from bi-tensor dMRI model has been shown to predict disease progression in PD and may help differentiate multiple system atrophy, progressive supranuclear palsy, and PD. However, f_iso-corrected dMRI metrics have not been investigated in PD-FOG, which is a debilitating symptom in PD with ineffective treatments. Neuroanatomical correlates of f_iso-corrected dMRI metrics, and disease duration and severity in PD-FOG is currently unknown.

Design/Methods dMRI data were acquired from 17 PD-FOG (13 males (M), 69.53±7.01 years) and 21 PD-nFOG (14M, 69.05±6.68 years) patients using a 3T Skyra MRI scanner. The presence of FOG was determined through clinical evaluation by a movement disorders specialist. dMRI was acquired at two shells using the following parameters: 71 diffusion-encoding-directions each at 2 b-values (b-values: 500s/mm² and 1000s/mm²), spatial resolution=1.5mm³, TE=100ms, multiband factor=3. Both f_iso-corrected and non f_iso-corrected dMRI metrics were compared to investigate WM organization difference between the two groups using nonparametric statistics. Furthermore, a multiple linear regression model was employed to understand the neuroanatomical correlates of f_iso-corrected dMRI metrics with disease duration and severity.

Results Non f_iso-corrected dMRI metrics were not different between the groups. However, f_iso-corrected dMRI metrics showed increased WM organization difference in in the left hemispheric frontal cortex and cingulate bundle of PD-FOG (compared to PD-nFOG). Similarly f_iso-corrected mean diffusivity (MD) was significantly greater in the left-hemisphere of PD-FOG. Significant correlation of free-water with disease severity was also observed in PD-FOG and not in PD-nFOG.

Conclusions Our findings suggest f_iso-corrected dMRI metrics are better diagnostic biomarkers for PD-FOG as compared to non f_iso-corrected dMRI metrics. Evaluating beyond single-tensor dMRI measures such as diffusion kurtosis measures with higher b-values (2500s/mm²) are currently underway.

Authors/Disclosures
Virendra R. Mishra, PhD (The University of Alabama at Birmingham) PRESENTER	The institution of Prof. Mishra has received research support from Keep Memory Alive Young Scholar Award. The institution of Prof. Mishra has received research support from NINDS/NIA: R01NS117547-01. The institution of Prof. Mishra has received research support from NIGMS: P20GM109025.
	No disclosure on file
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Jeffrey L. Cummings, MD, FAAN	Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol-Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia, Biogen, Genentech, Grifols, Janssen, Karuna, Otsuka, reMYND, Roche, Signant Health. Dr. Cummings has stock in Artery, Vaxxinity, Behrens, Alzheon, MedAvante-Prophase, and Acumen. Dr. Cummings has received research support from NIH. Dr. Cummings has received research support from NIGMS. Dr. Cummings has received intellectual property interests from a discovery or technology relating to health care.
Zoltan Mari, MD, FAAN (Cleveland Clinic Lou Ruro Center for Brain Health)	Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Mari has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ACADIA. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parkinson Study Group. Dr. Mari has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie. Dr. Mari has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for ACADIA. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for US World Meds. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Moore and Moore PLLC. Dr. Mari has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Francis Law Firm PLLC. Dr. Mari has stock in NeuroReserve. Dr. Mari has stock in Sensory Cloud. The institution of Dr. Mari has received research support from Cerevel. The institution of Dr. Mari has received research support from AbbVie. The institution of Dr. Mari has received research support from NIH. The institution of Dr. Mari has received research support from Parkinson's Foundation. The institution of Dr. Mari has received research support from Michael J Fox Foundation. The institution of Dr. Mari has received research support from LBDA. The institution of Dr. Mari has received research support from Eli Lilly.
Aaron Ritter, MD (Cleveland Clinic)	The institution of Dr. Ritter has received research support from NIH.
	No disclosure on file
Irene Litvan, MD, FAAN (UC San Diego Parkinson and Other Movement Disorder Center)	Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprinoia. Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Litvan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. Dr. Litvan has received personal compensation in the range of $50,000-$99,999 for serving as a Chief Editor with Frontiers in Neurology.
Brent R. Bluett, DO (Central California Movement Disorders)	No disclosure on file

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