This study used multishell diffusion MRI (dMRI) to model extra-axon (EAD), intra-axon (IAD), and free-water (FW) diffusion properties to delineate patterns of Parkinson’s disease (PD)-related changes in the substantia nigra (SN), a key pathological location in PD.  

Recent studies have shown increased FW in the SN of PD patients using bi-tensor dMRI with a single shell acquisition. Multishell dMRI allows for a more accurate estimation of FW in addition to the modeling of EAD and IAD diffusion components, and may provide richer information about SN changes in PD.

Multishell dMRI (3T with 3 b values: 400, 1200, and 2500) and clinical data were obtained from 45 PD patients and 41 controls. FW, EAD axial diffusivity (AD), EAD radial diffusivity (RD), IAD-AD, and IAD-RD images were estimated for each subject. Diffusion indices from ventral (vSN) and dorsal (dSN) SN were obtained for each subject from normalized diffusion maps. ANCOVA with adjustments for age and sex was used for group comparisons. Receiver operating characteristic (ROC) curve analyses were utilized for discriminability, whereas multiple regressions were used to correlate diffusion and clinical measures. The Bonferroni method corrected for multiple comparisons.

Compared to controls, FW in PD patients was increased in the dSN (p=0.005) but not in the vSN, whereas EAD-RD was increased in the vSN (p=0.003) but not in the dSN. ROC analyses showed FW alone provided a weak discrimination (AUC=0.65) between PDs and controls, whereas the discriminability was improved significantly when all diffusion measures were combined (AUC=0.80). None of MRI-clinical correlations reached significance after Bonferroni correction.

Multishell dMRI measures display rich, anatomically-dependent contextual information of the SN in PD. Future investigations are warranted and may lead to an improved understanding of PD-related pathology, and novel markers for diagnosing and/or monitoring PD progression in vivo.