Multimodal assessment of nigrosomal degeneration in Parkinson's disease

Approximately forty percent of all dopaminergic neurons in SNpc are located in five dense neuronal clusters, named nigrosomes. T₂- or T₂*-weighted images are used to delineate the largest nigrosome, named nigrosome-1. In these images, nigrosome-1 is a hyperintense region in the caudal and dorsal portion of the T₂- or T₂*-weighted substantia nigra. In PD, nigrosome-1 experiences iron accumulation, which leads to a reduction in T₂-weighted hyperintensity. Here, we examine neuromelanin-depletion and iron deposition in regions of interest (ROIs) derived from quantitative-voxel based morphometry (qVBM) on neuromelanin-sensitive images and compare the ROIs with nigrosome-1 identified in T₂*-weighted images.

Neuromelanin-sensitive and multi-echo gradient echo imaging data were obtained. R₂* was calculated from multi-echo gradient echo imaging data. qVBM analysis was performed on neuromelanin-sensitive images and restricted to SNpc. Mean neuromelanin-sensitive contrast and R₂* was measured from the resulting qVBM clusters. Nigrosome-1 was segmented in T₂*-weighted images of control subjects and its location was compared to the spatial location of the qVBM clusters.

Two bilateral clusters emerged from the qVBM analysis. These clusters showed reduced neuromelanin-sensitive contrast and increased mean R₂* in PD as compared to controls. Cluster-1 from the qVBM analysis was in a similar spatial location as nigrosome-1, as seen in T₂*-weighted images.

qVBM cluster-1 shows reduced neuromelanin-sensitive contrast and is in a similar spatial position as nigrosome-1. This region likely corresponds to nigrosome-1 while the second cluster may correspond to nigrosome-2.