A test-retest study on Parkinson's PPMI dataset yields statistically significant white matter fascicles

In this work, we propose a diffusion MRI protocol for mining Parkinson's disease diffusion MRI datasets and recover robust disease-specific biomarkers. Using advanced high angular resolution diffusion imaging (HARDI) crossing fiber modeling and tractography robust to partial volume effects, we automatically dissected 50 white matter (WM) fascicles. These fascicles connect deep nuclei (thalamus, putamen, pallidum) to different cortical functional areas (associative, motor, sensorimotor, limbic), basal forebrain and substantia nigra. Then, among these 50 candidate WM fascicles, only the ones that passed a test-retest reproducibility procedure qualified for further tractometry analysis. Leveraging the unique 2-timepoints test-retest Parkinson's Progression Markers Initiative (PPMI) dataset of over 600 subjects, we found statistically significant differences in tract profiles along the subcortico-cortical pathways between Parkinson's disease patients and healthy controls. In particular, significant increases in FA, apparent fiber density, tract-density and generalized FA were detected in some locations of the nigro-subthalamo-putaminal-thalamo-cortical pathway. This connection is one of the major motor circuits balancing the coordination of motor output. Detailed and quantifiable knowledge on WM fascicles in these areas is thus essential to improve the quality and outcome of Deep Brain Stimulation, and to target new WM locations for investigation.
Highlights • A diffusion MRI protocol to recover robust disease-specific biomarkers is proposed. • A test-retest reproducibility assessment is applied to 50 dissected WM fascicles. • Statistical analysis of tractometry results is performed on these robust fascicles. • Differences are found along the nigro-subthalamo-putaminal-thalamo-cortical pathway. • These results are crucial to improve existing treatments like Deep Brain Stimulation.