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

Abstract:

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.