Magnetic resonance imaging of cerebral perfusion and spatial coefficient of variation in cognitively impaired Parkinson’s disease

Parkinson’s disease (PD) affects 1% of the population over 60. Although classed as a movement disorder, cognitive impairment is a significant non-motor symptom of PD. While dysfunction of multiple brain systems most likely contributes to the development of dementia in Parkinson’s, recent evidence suggests that cerebrovascular health, particularly cerebral perfusion or cerebral blood flow (CBF), may play an important role in this process. Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging technique used clinically to image structures in the body. It is able to distinguish between different types of tissues in the brain. A perfusion MRI technique known as Arterial Spin Labeling (ASL) allows for non-invasive, quantified measurements of CBF. ASL works by labeling blood water as it enters the brain and waiting a delay time for the blood to reach the tissue before acquiring an image. The difference between this labeled image and a control image is proportional to the CBF. The time that the labeled blood arrives at the tissue is known as the Arterial Transit Time (ATT). The spatial coefficient of variance (sCoV) is a new metric derived from perfusion MRI, which reflects arterial arrival time of blood to tissue in the brain. In this thesis I have investigated the relationship between PD, cognitive decline and the cerebrovascular metrics: CBF, ATT and sCoV. I used perfusion MRI to investigate how CBF and sCoV vary across PD patients with different levels of cognitive function. Two different cohorts, containing both PD patients and controls, were recruited (cohort 1: PD = 185, HC = 49; cohort 2: PD=78, HC=27). All participants completed comprehensive cognitive testing to assess global cognitive ability and brain MRI to quantify cerebral perfusion and sCoV. Different MR machines were used for each cohort. For the second cohort, the MRI used allowed for direct measurement of ATT. Within the first cohort, CBF decreased and sCoV increased with cognitive decline in gray matter. In PD patients there was a significant reduction in CBF and increase in sCoV in the parietal and occipital lobes relative to controls. In the second cohort, there was a consistent decrease of CBF in the occipital lobes and increased sCoV across all lobes for the PD group. However, there was no significant relationship between the direct measurement of ATT and group or cognitive ability. We were able to establish an association between sCoV and ATT, however its magnitude was smaller than previously reported. The acquisition for cohort 2 was not optimized for measurement of CBF; this may have affected the results. Although a significant difference between groups and an association with cognitive ability was identified, CBF, sCoV and ATT provided little additional predictive value, on the individual level, of cognitive ability in PD compared to age and sex alone. While these findings suggest that there is no strong evidence for the clinical use for ASL in PD, they do provide information about disease progression. They indicate that perfusion in parietal and occipital regions is associated with cognitive function in PD, supporting further study examining vascular changes in PD. Interestingly, sCoV was found to be a more useful perfusion measure than CBF, which supports further investigation in other diseases with prolonged ATT. The recent development of new ASL techniques and design of optimal MR protocols will be of interest to explore in future MRI PD studies