Ultra-high-field (9.4 T) ex vivo diffusion MRI tractography reveals microstructural differences in Parkinson’s disease motor subtypes

The structural correlates of Parkinson's disease (PD) with tremor-dominance and those with non-tremor dominance are not fully differentiated. Ultra-high field magnetic resonance imaging (UHF-MRI) allows the human brain to be imaged at a higher resolution compared to traditional scanner strengths but has largely been underutilized in PD research. Scanning post-mortem tissue allows for increased scan times and fewer movement issues leading to improved image quality, especially higher spatial resolution. We performed diffusion MRI on twelve post-mortem hemispheres (eight parkinsonian (four tremor-dominant, four non-tremor-dominant) and four non-demented controls) scanned with a specialized 9.4 Tesla human post-mortem brain coil. Diffusion tensor analysis was performed for local scalar diffusion metrics and constrained spherical deconvolution tractography was performed for global connectivity metrics. Compared to both non-tremor-dominant patients and controls, tremor-dominant patients displayed greater hemispheric fractional anisotropy. While motor subtypes were similar to each other across multiple regional diffusion metrics, each subtype demonstrated subtype-specific differences when compared to controls. Interconnections within basal ganglia circuitry mainly involving the internal capsule showed disparities across both subtypes and controls. Our findings show motor subtype specific circuitopathies in PD and improve the mapping of connectivity fingerprints potentially relevant in the planning of treatment regimes.