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Title: MRI measures of neurovascular changes in idiopathic Parkinson's disease
Author: Al-Bachari, Sarah
ISNI:       0000 0004 6060 1502
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2017
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Idiopathic Parkinson’s disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved in IPD is not well defined. Indeed within the umbrella term of IPD great heterogeneity of motor (and non-motor) features exists, suggesting that different phenotypes may have differing underlying pathophysiologies. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques can reveal changes in structural or physiological neurovascular measures, herein also referred to as ‘altered neurovascular status (NVS)’, in IPD.Based on preliminary data from our initial exploratory study in a small IPD cohort, phenotypic differences in structural and physiological MRI measures of NVS were investigated in a larger study. The 3 Tesla (3T) MRI protocol included T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging to assess white matter lesion (WML) burden, arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT) and dynamic contrast enhanced (DCE) measures of blood-brain barrier (BBB) integrity. Analysis was undertaken of IPD clinical phenotypes, by comparison with two control groups. In total, fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant [TD], 24 postural instability and gait disorder [PIGD] and 6 intermediates) were compared with 2 control groups, the first comprising 18 control positive (CP) subjects with a history of clinical cerebrovascular disease (CVD) (mean age 70.1 ± 8.0 years) and the second comprising 34 control negative (CN) subjects without a history of clinical CVD (mean age 67.4 ± 7.6 years). IPD patients showed diffuse regions of significantly prolonged AAT and lower CBF by comparison with CN subjects, and a few regions of prolonged AAT by comparison with CP subjects, despite significantly fewer vascular risk factors. TD patients showed regions of significantly prolonged AAT and lower WML volume by comparison with PIGD patients. IPD patients also showed increased leakiness of the BBB in basal ganglia regions compared to the CN group, with a similar pattern in both IPD phenotypes. These data provide evidence of altered NVS in IPD, with IPD phenotype specific differences.
Supervisor: Emsley, Hedley ; Parkes, Laura Sponsor: University of Manchester Biomedical Imaging Institute ; MRC ; Sydney Driscoll Neurosicence Charity
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Neurovascular Status ; MRI ; Idiopathic Parkinson's disease ; Phenotypes