Imaging nigral pathology and clinical progression in Parkinson's disease

Abstract

The pattern of dopamine cell loss in Parkinson's disease (PD) is known to be prominent in the ventrolateral and caudal substantia nigra (SN), but less severe in the dorsal and rostral region. Both diffusion tensor imaging (DTI) and R2* relaxometry of the SN have been reported as potential markers for PD, but their relative ability to mark disease progression and differences in pathophysiological bases remains unclear. High-resolution T2-weighted, R2*, and DTI were obtained from 28 controls and 40 PD subjects [15 early stage [disease duration ≤1 year], 14 mid stage [duration 2-5 years], and 11 late stage [duration >5 years]). Fractional anisotropy and R2* values in both rostral and caudal SN were obtained for all subjects, and clinical measures (e.g., disease duration, levodopa-equivalent daily dosage, and "off"-drug UPDRS motor score) were obtained for Parkinson's subjects. There was no correlation between fractional anisotropy and clinical measures, whereas R2* was strongly associated with disease progression. Compared to controls, fractional anisotropy in caudal SN was significantly decreased in PD patients of all stages, whereas in rostral SN, it was decreased significantly only in the late-stage group. R2* in both SN regions was significantly increased in the mid- and late-stage, but not early-stage, of PD subjects. These findings suggest that fractional anisotropy changes may mark early pathological changes in caudal SN, whereas the changes in R2* may more closely track PD's clinical progression after symptom onset.

Figure 1

Procedure used to segment the rostral and caudal regions of the SN. A: Illustration of the position of slices used for the definitin of ROIs. B and C: Illustration of the three dimesional relationship of the ROIs and the separation of the rostral and caudal regions of the SN. D(1-6): Illustration of the exact locations of the SN ROI.

Figure 2

Correlations between clinical measurements and MRI measurements. The scatterplots depict the age-adjusted residuals. The shaded areas represent the 95% confidence interval for each regression line.

Figure 3

Comparison of R2* and FA values in different segments of the SN in PDs and Controls. Error bars represent the SEM. PD_ES - “early-stage,” are newly diagnosed PD subjects within the first year of diagnosis; PD_MS - “mid-stage,” are those that are in the rapidly progressing stage, 2-5 years following diagnosis; and PD_L – “late-stage,” are PD subjects who are >5 years since initial diagnosis.. Signficant differences between PD and control subjects are represented as: *: p<0.05; ***: p<0.001.