Background: Motor symptoms in Parkinson disease (PD) have exhibited lateral asymmetry, suggesting asymmetric neuronal loss in the substantia nigra (SN). Difl-Usion MRI may be able to help confirm tissue microstructural alterations in the substantia nigra to probe for the presentee of asymmetry. Purpose: To investigate lateral asymmetry in the SN of patients with PD by using diffusion MRI with both Gaussian and non-Gaussian models. Materials and Method: In this cross-sectional study conducted from March 2015 to March 2017,27 participants with PD and 27 age-matched healthy control (HC) participants, all right handed, underwent MRI at 3.0 T. High-spatial-resolution diffusion images were acquired with a reduced field of view by using seven b values up to 3000 sec/mm(2). A continuous-time random-walk(CTRW) non-Gaussian diffusion model was used to produce anomalous diffusion coefficient (D-m) and temporal (alpha) and spatial (beta) diffusion heterogeneity indexes followed by a Gaussian diffusion model to yield an apparent diffusion coefficient (ADC). Individual or linear combinations of diffusion parameters in the SN were unilaterally compared between the PD and HC groups Results: In the bilateral comparison between the PD and HC groups, differences were observed in beta (0.7 +/- 0.06 [standard deviation] vs 0.64 +/- 0.04, respectively; P=.016), ADC(0.48 mu m(2)/msec +/- 0.08 vs 0.53 mu m(2)/msec 0.06, respectively; P= .03), and the combination of CTRW parameters (P= .02). In the unilateral comparison, differences were observed in all diffusion parameters on the left SN (P < .03), but not on the right (P > .20). In a receiver operating characteristic (ROC) analysis to delineate left SN abnormality in PD, the combination of D-m, and alpha and beta produced the best sensitivity (sensitivity, 0.78): the combination of D-m and beta produced the best specificity (specificity,0.85); and thecombination of alpha and beta produced the largest area under the ROC curve (area under the ROC curve, 0.73). Conclusion: These results suggest that quantitative diffusion MRI is sensitive to brain tissue changes in participants with Parkinson disease and provide evidence of substantia nigra lateral asymmetry in this disease. (C) RSNA, 2019