This study aimed to discriminate between neuroinflammation and neuronal degeneration in the white matter (WM) and gray matter (GM) of patients with Parkinson's disease (PD) using free-water (FW) imaging. Analysis using tract-based spatial statistics (TBSS) of 20 patients with PD and 20 healthy individuals revealed changes in FW imaging indices (i.e., reduced FW-corrected fractional anisotropy (FAT), increased FW-corrected mean, axial, and radial diffusivities (MDT, ADT, and RDT, respectively) and fractional volume of FW (FW) in somewhat more specific WM areas compared with the changes of DTI indices. The region-of-interest (ROI) analysis further supported these findings, whereby those with PD showed significantly lower FAT and higher MDT, ADT, and RDT (indices of neuronal degeneration) in anterior WM areas as well as higher FW (index of neuroinflammation) in posterior WM areas compared with the controls. Results of GM-based spatial statistics (GBSS) analysis revealed that patients with PD had significantly higher MDT, ADT, and FW than the controls, whereas ROI analysis showed significantly increased MDT and FW and a trend toward increased ADT in GM areas, corresponding to Braak stage IV. These findings support the hypothesis that neuroinflammation precedes neuronal degeneration in PD, whereas WM microstructural alterations precede changes in GM.
Keywords: Parkinson’s disease; diffusion tensor imaging; free-water imaging; gray matter-based spatial statistics; neuroinflammation; neuronal degeneration; tract-based spatial statistics.