MRI mapping of nigrostriatal pathway degeneration in early-stage Parkinson's disease

Neuronal degeneration in Parkinson's disease begins mainly in the ventrolateral region of the substantia nigra pars compacta and progressively spreads out to other mesencephalic areas. Concurrently, striatal dopaminergic denervation follows a distinct gradient, beginning in the posterior putamen and extending to the anterior putamen and the caudate nucleus as the disease progresses. However, changes along the nigrostriatal projections remain poorly characterized. In this study, we reconstructed the nigrostriatal pathway using a healthy control dataset and we explored the topographic distribution of changes associated with the onset of Parkinson's disease. Two independent cohorts of patients with recently diagnosed early-stage Parkinson's disease underwent magnetic resonance imaging sessions to assess different aspects putatively linked to neurodegeneration, including markers for microstructural integrity (fractional anisotropy and mean diffusivity) and iron content (R2* and R2). We also included the T1w/T2w ratio, a metric that has been scarcely explored in Parkinson's disease and may reflect microstructural and myelin-related changes, among other neurodegenerative-related features. We found widespread changes in microstructure, iron load, and T1w/T2w along the entire projection, with greater prominence near the substantia nigra pars compacta. These changes affected both hemispheres but had greater severity in the side contralateral to the more clinically affected hemibody. The spatial distribution and magnitude of these alterations in Parkinson's disease patients closely aligned with the iron load in controls. Interestingly, the T1w/T2w ratio demonstrated the strongest effects across cohorts, highlighting its potential as a biomarker for neurodegeneration. These findings provide a promising framework for tracking nigrostriatal degeneration in vivo.