Substantia nigra ferric overload and neuromelanin loss in Parkinson’s disease measured with 7T MRI


Background Vulnerability of the substantia nigra dopaminergic neurons in Parkinson’s disease is associated with ferric overload, leading to neurodegeneration with cognitive and motor decline. Here, we quantify iron and neuromelanin-related markers in vivo using ultra-high field 7-Tesla MRI, and examine the clinical correlates of these imaging assessments. Methods Twenty-five people with mild-to-moderate Parkinson’s disease and twenty-six healthy controls underwent high-resolution imaging at 7-Tesla with a T 2 *-weighted sequence (measuring susceptibility-χ and R 2 *, sensitive to iron) and a magnetization transfer-weighted sequence (MT-w, sensitive to neuromelanin). From an independent control group (N=29), we created study-specific regions-of-interest for five neuromelanin- and/or iron-rich subregions within the substantia nigra. Mean R 2 *, susceptibility-χ and their ratio, as well as the MT-w contrast-to-noise ratio (MT-CNR) were extracted from these regions and compared between groups. We then tested the relationships between these imaging metrics and clinical severity. Results People with Parkinson’s disease showed a significant ~50% reduction in MT-CNR compared to healthy controls. They also showed a 1.2-fold increase in ferric iron loading (elevation of the ratio from 0.19±0.058ms/ppm to 0.22±0.059ms/ppm) in an area of the substantia nigra identified as having both high neuromelanin and susceptibility MRI signal in healthy controls. In this region, the ferric-to-ferrous iron loading was associated with disease duration (β=0.0072, p FDR =0.048) and cognitive impairment (β=−0.0115, p FDR =0.048). Conclusions T 2 *-weighted and MT-weighted high-resolution 7T imaging markers identified neurochemical consequences of Parkinson’s disease, in overlapping but not-identical regions. These changes correlated with non-motor symptoms.