Structural magnetic resonance imaging in Parkinson’s disease and rapid eye movement sleep behaviour disorder
Abstract
Rapid eye movement sleep behaviour disorder (RBD) is a prodromal manifestation of Parkinson’s disease (PD). RBD patients show changes to the substantia nigra pars compacta (SNc) and striatum, which are impacted areas in PD. Thus, this dissertation will quantify changes to these structures using structural magnetic resonance imaging (MRI), which will determine if MRI is sensitive to pathophysiological changes, if parcellation can isolate affected subregions, and if these features support these disorders lying on a continuum.
In Chapter 2, we assessed mean susceptibility, a proxy for iron, using quantitative susceptibility mapping (QSM) in RBD and PD patients. We identified SNc iron elevation in both RBD and PD. Changes to structures which are affected later, such as the ventral tegmental area (VTA), were present only in PD. Clearly, the SNc, the main site of degeneration in PD, is impacted in RBD.
In Chapter 3, we assessed striatum and VTA/SNc subregion diffusion MRI metrics using probabilistic tractography in RBD patients from local and Parkinson’s Progression Markers Initiative (PPMI) data. The caudal motor SNc subregion was the only area impacted in both datasets, based on the increased surface mean diffusivity feature in RBD patients. Thus, altered microstructural integrity is present in RBD patients in a region that overlaps with the ventrolateral SNc, the site with greatest neurodegeneration in PD.
In Chapter 4, we assessed iron in the standard striatum along with our parcellated striatum subregions in RBD and PD patients. The caudal motor striatum demonstrated lower susceptibility in PD patients, with no changes in RBD, or the other regions. Our parcellation isolated the most affected region and suggests pathophysiological changes to iron may be restricted to the SNc in RBD patients.
Overall, these projects quantify changes to the SNc and striatum of RBD and PD patients. Furthermore, they highlight the sensitivity of structural MRI to disease, improvements to diagnostic methodology when using our parcellation, and neuroimaging features which suggest that these disorders lie on a continuum. Once validated, these candidate biomarkers could provide benefits to diagnostic methods, patient care, quality of life, and assist development of disease-modifying therapy where none currently exist.