Multimodal dopaminergic and free-water imaging in Parkinson's disease

Abstract Introduction When using free-water diffusion imaging or positron emission tomography (PET), it is established that substania nigra microstructure and presynaptic dopamine activity are impaired in early PD. It is not well understood if these two forms of degeneration are redundant, or if they each provide a unique contribution to the clinical motor and cognitive symptoms. Methods A total of 129 PD and 75 control individuals underwent motor and cognitive evaluations, and in vivo [11C] dihydrotetrabenazine(DTBZ) monoaminergicbrain PET imaging and diffusion imaging. Correlations between free-water in the substantia nigraand striatal PET measures were analyzed. Unbiased multiple regression using a backward elimination method was performed between clinical severity and all imaging measures. Results Inverse correlations were found between free-water in posterior substantia nigraand DTBZ binding in putamenand caudate. Multiple regression revealed that increased free-water in the posterior substantia nigra, decreased DTBZ binding in putamen, and age were predictors of higher Hoehn and Yahr stage, MDS-UPDRS III scores, and posture and gait sub-scores. Increased posterior substantia nigrafree-water alone was associated tremor scores. Free-water in caudate and putamendid not predict measures of motor performance. Decreased DTBZ binding in caudate, increased free-water in caudate and posterior substantia nigrawere associated with higher dementia ratings. Conclusions These findings suggest that free-water in the posterior substantia nigraand presynaptic dopamine imaging in striatum are uniquely associated with the clinical symptoms of PD, indicating that each imaging modality may be measuring a unique mechanism relevant to nigrostriatal degeneration.