Summary Diffusion tensor imaging could be useful in characterizing movement disorders because it non-invasively examines multiple brain regions simultaneously. We report a multi-target imaging approach focused on the basal ganglia and cerebellum in Parkinson’s disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, essential tremor, and healthy controls. Seventy-two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristics analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control vs. movement disorder (92% sensitivity, 88% specificity), control vs. parkinsonism (93% sensitivity, 91% specificity), Parkinson’s disease vs. atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson’s disease vs. multiple system atrophy (94% sensitivity, 100% specificity), Parkinson’s disease vs. progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy vs. progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson’s disease vs. essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson’s disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects.

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