Doctor of Philosophy
MacDonald, Penny A.
Khan, Ali R.
Owen, Adrian M.
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.
Summary for Lay Audience
Parkinson’s disease (PD) may present in its earliest form as a sleep illness called rapid eye movement sleep behaviour disorder (RBD). Patients with RBD have shown changes in brain images, which resemble the earliest indications of PD. Thus, our work aims to measure changes seen in magnetic resonance imaging (MRI) to determine if the regions impacted by PD are also affected in RBD and if MRI can detect these changes.
In Chapter 2, we looked at an indirect measure of brain iron in RBD and PD patients. We found increased iron in RBD and PD in the main site of degeneration called the substantia nigra pars compacta (SNc). Changes to other brain areas were only seen in PD.
In Chapter 3, we looked at the connections of the SNc and striatum given the importance of these brain regions in PD. We assessed MRIs of RBD patients from local and open access data. One subregion of the SNc, the caudal motor, was similarly impacted in both datasets for RBD patients. This subregion overlaps with the site of greatest degeneration in PD.
In Chapter 4, we looked at an approximation of brain iron in the striatum with and without our subregional approach from Chapter 3 in RBD and PD patients. The caudal motor subregion of the striatum also showed changes in PD, but not RBD. No differences were found without our approach. Our subregional approach identified the most affected region and suggested changes in iron may be present only in the SNc of RBD patients. This finding makes sense because the SNc is affected before the striatum in PD.
Overall, these chapters quantify changes to the SNc and striatum of RBD and PD patients. Furthermore, they highlight the sensitivity of MRI to disease, improvements to techniques using our subregional approach, and MRI features which relate RBD to PD on a continuum. Following confirmation with larger datasets, these features could benefit diagnosis, patient care, quality of life, and therapy development to alter and potentially cure PD.
Alushaj, Erind, "Structural magnetic resonance imaging in Parkinson’s disease and rapid eye movement sleep behaviour disorder" (2023). Electronic Thesis and Dissertation Repository. 9477.
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Available for download on Friday, August 22, 2025