Development and application of functional MRI methods to investigate brainstem haemodynamics in the context of systemic hypertension

Woodward, Owen ORCID: https://orcid.org/0000-0001-7981-2201 2023. Development and application of functional MRI methods to investigate brainstem haemodynamics in the context of systemic hypertension. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

The selfish brain mechanism proposes that in some cases hypertension could develop as a compensatory mechanism that aims to maintain cerebral blood flow (CBF) by increasing systemic blood pressure through an increase in cardiovascular sympathetic tone. The mechanism that might trigger this hypothesised initial reduction in CBF is uncertain, but the brainstem is an important component of the central autonomic nervous system and may therefore play an important role in the development of hypertension via the selfish brain mechanism. Various techniques have been used to investigate the selfish brain mechanism in humans, including magnetic resonance imaging (MRI) methods to measure CBF and cerebrovascular reactivity (CVR). CVR quantifies the change in CBF in response to a vascular stimulus, and is related to the responsiveness, tone and functional reserve of the cerebrovascular system. This thesis aims to validate, optimise and apply a variety of MRI-based methods of quantifying human cerebrovascular function, which may then be used in future studies to further investigate the selfish brain mechanism. Firstly, methods of measuring CBF and CVR using MRI are tailored towards their application in the brainstem and the feasibility of measuring regional brainstem CBF and CVR is demonstrated. Next, existing data is explored to study the association between vertebral artery hypoplasia (VAH) and brainstem CBF in hypertensives but no statistically significant association between regional CBF, VAH and hypertension is found. Brainstem co-registration is then optimised using machine learning. The UK biobank dataset is explored to study the amplitude of low-frequency fluctuations (ALFF) in the BOLD signal, a potential surrogate index of CVR, in hypertensives. There is no statistically significant difference in the regional variation in ALFF between hypertensives and normotensives. Following this, the relationship between ALFF and CVR is investigated to validate ALFF as a surrogate marker of CVR, but no evidence to support the use of ALFF as a specific metric of CVR is demonstrated. Finally, a pilot study of functional MRI in the locus coeruleus, an important noradrenergic brainstem nucleus that is integral to the central autonomic network, is undertaken. The feasibility of mapping functional connectivity of the LC using an anatomical localiser tailored to each participant is demonstrated.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Psychology
Date of First Compliant Deposit:	13 May 2024
Last Modified:	13 May 2024 09:47
URI:	https://orca.cardiff.ac.uk/id/eprint/168860

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