In Vivo Detection of Lateral-Ventral Tier Nigral Degeneration in Parkinson's Disease

The objective of this study was to measure neuromelanin-sensitive MRI contrast changes in the lateral-ventral tier of substantia nigra pars compacta in Parkinson's disease (PD). Histopathological studies of PD have demonstrated both massive loss of melanized dopamine neurons and iron accumulation in the substantia nigra pars compacta. Neurodegeneration is most profound in the lateral-ventral tier of this structure. We have previously shown in both healthy controls and individuals with PD that neuromelanin-sensitive MRI and iron-sensitive MRI contrast regions in substantia nigra overlap. This overlap region is located in the lateral-ventral tier. Exploiting this area of contrast overlap for region of interest selection, we developed a semi-automated image processing approach to characterize the lateral-ventral tier in MRI data. Here we apply this approach to measure magnetization transfer contrast, which corresponds to local neuromelanin density, in both the lateral-ventral tier and the entire pars compacta in 22 PD patients and 19 controls. Significant contrast reductions were seen in PD in both the entire pars compacta (P = 0.009) and in its lateral-ventral tier (P = 0.0002); in PD contrast was significantly lower in the lateral-ventral tier than in the entire pars compacta (P = 0.0008). These findings are the first in vivo evidence of the selective vulnerability of this nigral subregion in PD, and this approach may be developed for high impact biomarker applications. (C) 2017 Wiley Periodicals, Inc.