Imaging Parkinsonian Pathology in Substantia Nigra with MRI

Abstract

The substantia nigra pars compacta (SNc) and its projection to the striatum undergo profound degeneration in Parkinson’s disease (PD). Literature on imaging PD-related changes in the nigrostriatal system using iron-sensitive and diffusion-sensitive MRI contrasts has been contentious, with both negative and positive results reported in each contrast. These incompatible findings may be due to the inaccurate placement of regions of interest for the SNc. Histologically, SNc is characterized by the presence of melanized dopamine neurons, whereas the substantia nigra pars reticulata is characterized by high iron content. Despite this histology, previous studies have frequently relied upon iron-sensitive MRI contrast when segmenting the SNc. This is also problematic since recent work found iron-sensitive and neuromelanin-sensitive contrasts are largely non-overlapping in substantia nigra. Since neuromelanin-sensitive MRI contrast colocalizes with the melanized dopamine neurons of the SNc upon radiologic–histologic correlation, the use of neuromelanin-sensitive MRI will allow for accurate localization of SNc and better capture parkinsonian pathobiology than iron-sensitive MRI. This article outlines iron-sensitive and diffusion-sensitive MRI contrasts, and provides an overview of neuromelanin-sensitive MRI techniques. The application of these techniques to image parkinsonian pathobiology in substantia nigra is then reviewed, with a focus on neuromelanin-sensitive imaging methods for the accurate and reproducible study of PD-related changes in SNc. These advances may help resolve current controversies surrounding MRI investigations of substantia nigra in PD and related disorders.