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