Mapping track density changes in nigrostriatal and extranigral pathways in Parkinson's disease

In Parkinson's disease (PD) the demonstration of neuropathological disturbances in nigrostriatal and extranigral brain pathways using magnetic resonance imaging remains a challenge. Here, we applied a novel diffusion-weighted imaging approach—track density imaging (TDI). Twenty-seven non-demented Parkinson's patients (mean disease duration: 5 years, mean score on the Hoehn & Yahr scale = 1.5) were compared with 26 elderly controls matched for age, sex, and education level. Track density images were created by sampling each subject's spatially normalized fiber tracks in 1 mm isotropic intervals and counting the fibers that passed through each voxel. Whole-brain voxel-based analysis was performed and significance was assessed with permutation testing. Statistically significant increases in track density were found in the Parkinson's patients, relative to controls. Clusters were distributed in disease-relevant areas including motor, cognitive, and limbic networks. From the lower medulla to the diencephalon and striatum, clusters encompassed the known location of the locus coeruleus and pedunculopontine nucleus in the pons, and from the substantia nigra up to medial aspects of the posterior putamen, bilaterally. The results identified in brainstem and nigrostriatal pathways show a large overlap with the known distribution of neuropathological changes in non-demented PD patients. Our results also support an early involvement of limbic and cognitive networks in Parkinson's disease.