Diffusion-weighted imaging and its relationship to microglial activation in parkinsonian syndromes

Microglial activation has been implicated in the pathogenesis of Parkinson's disease (PD) and atypical parkinsonian syndromes, and regional microstructural changes have been identified using diffusion-weighted MR imaging. It is not known how these two phenomena might be connected. We hypothesized that changes in regional apparent diffusion coefficient (rADC) in atypical parkinsonian syndromes would correlate with microglial activation. In our study we have evaluated changes in rADC in 11 healthy controls, 9 patients with PD and 11 with either multiple system atrophy or progressive supranuclear palsy. The patients also underwent [(11)C]-(R)-PK11195 positron emission tomography, a marker of microglial activation. Increased rADC was found compared to controls in the thalamus and midbrain of all parkinsonian patients, and in the putamen, frontal and deep white matter of patients with atypical parkinsonian syndromes. Putaminal rADC alone did not reliably differentiate PD from atypical parkinsonism. There was no correlation between [(11)C]-(R)-PK11195 binding potential and rADC in the basal ganglia in atypical parkinsonian syndromes. However, pontine PK11195 binding and rADC were positively correlated in atypical parkinsonism (r = 0.794, p = 0.0007), but not PD patients. In conclusion, microglial activation does not appear to contribute to the changes in putaminal water diffusivity associated with atypical parkinsonian syndromes, but may correlate with tissue damage in brainstem regions.