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Neuroimaging Biomarkers in Parkinsonism: Differentiating Subtypes and Tracking Disease Progression (U01)

David Vaillancourt
PI:
David Vaillancourt, PhD
University of Florida, (Gainesville, Florida)
Daniel Corcos
PI:
Daniel Corcos, PhD
Northwestern University, (Chicago, Illinois)

Summary

There is an urgent need for biomarkers of diagnosis and progression of Parkinson’s disease (PD) and related disorders to improve clinical-trial ready biomarkers for PD, MSA, and PSP.  Overlap of symptoms in early stages makes diagnosing these diseases challenging, yet accurate diagnosis is critical for effective targeting of disease-modifying therapies. Further, clinical-trials for a medication in PD may not apply to MSA and PSP. Thus, developing biomarkers to differentiate disease is a critical step to making sure that a clinical-trial is testing the medication on patients with the correct diagnosis. To develop disease differentiation and progression biomarkers for PD and related disorders, we will use two imaging modalities, free-water imaging and task-fMRI in two brain regions, the basal ganglia and cerebellum. Free-water imaging applies a two-compartment model of diffusion to estimate the fractional volume of unconstrained diffusion (free-water), and fractional anisotropy of the tissue corrected for the free-water compartment. Task-fMRI assesses the blood oxygenation level dependent (BOLD) activity in key regions of the brain involved in the production of grip force.  The ability to use these imaging techniques for monitoring disease progression will be determined over a 12 month period and the utility of these imaging modalities for patient stratification will be studied in PD, PSP and MSA patient cohorts.

Study Information

Title: Neuroimaging Biomarkers in Parkinsonism: Differentiating Subtypes and Tracking Disease Progression
PI Name: David Vaillancourt
Repository: Parkinson's Disease Biomarker Program
Status: Controlled Access
Funding Source: NIH-NINDS
Abstract: The goal of this application is two-fold. First, we will test and validate across two imaging sites a set of diagnostic and progression biomarkers we have recently published that differentiate and track disease progression in Parkinson's disease (PD), parkinsonian variant of multiple system atrophy (MSAp) and progressive supranuclear palsy (PSP). Second, we will use a set of novel imaging biomarkers to further understand the neurobiology of how each of these three diseases differ and progress over time. With respect to goal 1, over the past 5 years our group has led the efforts in magnetic resonance imaging (MRI) for the Parkinson's Disease Biomarker Program (PDBP) and has developed 2 innovative biomarkers for differentiating PD, MSAp, and PSP. Both free-water diffusion imaging and task-fMRI have uncovered clear patterns of degeneration and abnormal functional activation in the basal ganglia and cerebellum that can reliably differentiate PD, MSAp, and PSP. In longitudinal studies we found that free-water diffusion imaging and task- fMRI track progression of PD, MSAp, and PSP over one year with no changes in age and sex matched controls. Reproducible, reliable, objective and validated MRI-based progression markers are of great significance and would transform clinical trials in PD, MSAp, and PSP. With respect to goal 2, in addition to evaluating free-water and task-based fMRI using our standardized protocol across two imaging sites, we will also test new biomarkers that leverage advanced imaging pulse sequences using simultaneous multi-slice imaging for acquiring data faster and at a higher spatial resolution. Such technical advances provide a richer examination of the nigrostriatal, cortico-striatal, and cerebellar-thalamo-cortical anatomical tracts for disease differentiation, and for understanding how the disease spreads along disease-specific tracts over time. Leveraging simultaneous multi-slice imaging will facilitate multi-shell diffusion imaging models for examining free-water, neurite density and orientation dispersion, as well as task-fMRI connectivity for examining the functional connections across a network. We will provide timely data sharing with the PDBP community. We have a very experienced team of experts in neurology and neuroimaging, and a long history of publishing together in high impact journals.
Study ID: PDBP-STUDY0000235
Data Type: Clinical Assessment, Imaging
Study Type: Natural History
Grant ID: U01 NS102038
Study Started On: 2017-10-01
Study Completed On: 2021-06-30
Estimated number of Subjects: 350

Abstract

The goal of this application is to test and validate across two imaging sites a set of diagnostic and progression biomarkers we have recently published that differentiate and track disease progression in Parkinson's disease (PD), parkinsonian variant of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Over the past 5 years our group has led the efforts in magnetic resonance imaging (MRI) for the Parkinson's Disease Biomarker Program (PDBP) and has developed 2 innovative biomarkers for differentiating PD, MSA, and PSP. Both free-water diffusion imaging and task-fMRI have uncovered clear patterns of degeneration and abnormal functional activation in the basal ganglia and cerebellum that can reliably differentiate PD, MSA, and PSP. In longitudinal studies we found that free-water diffusion imaging and task- fMRI track progression of PD, MSA, and PSP over one year with no changes in age and sex matched controls. Reproducible, reliable, objective and validated MRI-based progression markers are of great significance and would transform clinical trials in PD, MSA, and PSP. At our two imaging sites, we will acquire data on 100 PD, 50 MSA, 50 PSP, and 50 healthy age and sex matched controls. We will provide timely data sharing with the PDBP community.

Goals

1. Cohort Development: 100 PD, 50 PSP and 50 MSA patients and follow up after 12 months.  Participants will be assessed using stand PDBP core clinical measures, biosamples (DNA, RNA and plasma) will be collected at the baseline and 12 month visit and deposited with the NINDS BioSEND Repository.


2. Imaging: Free water and task-fMRI imaging will be completed at the baseline and 12 month visit.  Clinical and imaging data will be deposited with the PDBP data management resource 
 

Participate

This study is no longer recruiting participants

Please contact:

Nieci Black
Clinical Coordinator
University of Florida (Primary)
Email
nblack@ufl.edu

Available Data Types