Objective: To compare the within-subject longitudinal sensitivity of PD biomarkers derived from DaTscan and Diffusion MRI.

Background: Parkinson’s Disease (PD) is associated with impaired striatal dopamine as measured by DaTscan, and with altered brain structure as measured by volumetric MRI and diffusion tensor imaging (DTI). Free water estimation using a bi-tensor diffusion model is gaining traction as a proxy measure for neuroinflammation, which could serve as an additional imaging biomarker to characterize stage and progression of degenerative pathologies. We assessed longitudinal changes in the fraction of bound versus free water in PD patients and compared against DaTscan SPECT uptake within the putamen.

Method: In the Parkinson’s Progression Markers Initiative (PPMI), we identified 37 de-novo PD patients with three DTI exams (30 directions) and three DaTScan SPECT exams at baseline, one-year and two-year follow up. DTI directional volumes were realigned independently using a 6-parameter rigid body approach., The realigned diffusion weighted volumes in addition to the 3DT1 were co-registered to the b=0 scan.  Whole-brain free water (FW) maps and FW-corrected maps of fractional anisotropy (FA) and mean diffusivity (MD) were derived by fitting a bi-tensor model of signal attenuations from bound and free water [1], normalized to template space, and smoothed using a Gaussian kernal. Atlas-space (AAL2) regions of interest were applied to derive regional free water and free water corrected metrics at each visit. Minimum putamen SBR was used to index DaTscan uptake for each timepoint. Regional metrics were entered into regression analysis to derive the rate of change for each subject.

Results: PD patients demonstrated significant reduction in DaTscan SBR at one- and two-year follow up. A significant increase in free water fraction was also observed in many brain regions, both within the striatum (bilateral caudate, putamen, accumbens) and beyond (temporal, frontal, insular cortices). Following Bonferroni correction for multiple comparisons, FW in the medial pre-frontal cortex and accumbens showed significantly stronger group-level effects than DaTscan SBR.

Conclusion: PD involves marked disruption to tissue volumes, tract integrity and free water accumulation throughout the brain. Advanced MRI-based biomarkers can serve as robust indicators of disease progression in clinical trials.

References: [1] Pasternak et al., Free Water Elimination and Mapping from Diffusion MRI, MRM, 2009

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-direct-longitudinal-comparison-of-free-water-diffusion-mri-and-datscan-spect-in-parkinsons-disease/