Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease

Parkinson's disease (PD) is histopa- thologically characterized by the loss of dopamine neu- rons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregu- lation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography pro- tocol for reliably tracking the nigrostriatal fibers on mul- ticenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integri- ties of the nigrostriatal fibers in PD patients are associ- ated with the severity of motor disability and putaminal dopamine binding ratios. Diffusion tensor tractography was performed on 50 drug-na€ ove PD patients and 27 healthy control subjects from the international multicen- ter Parkinson's Progression Marker Initiative. Tractogra- phy consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisot- ropy, along with radial and axial diffusivity of the nigro- striatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were asso- ciated with the degree of motor deficits in PD patients. Taken together, the findings imply that the diffusion ten- sor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. V C 2015 International Parkinson and Movement Dis- order Society Key W ords: Parkinson's disease; MRI; diffusion ten- sor imaging; diffusion tensor tractography; nigrostriatal pathway