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Milbourn, Colette Clare (2025) Robust Quantification of Cerebrovascular Reactivity using Magnetic Resonance Imaging and Hypercapnic Challenges. PhD thesis, University of Nottingham.

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Abstract

Pseudocontinuous Arterial Spin Labelling (pCASL) magnetic resonance imaging (MRI) can quantify tissue cerebral blood flow (CBF) in the brain, providing a potential clinical biomarker of brain health. A cerebrovascular reactivity (CVR) response can be induced by increasing blood flow via a vasoactive stimulus, e.g. inhaling carbon dioxide during hypercapnic challenges. The overall aim of this thesis was to validate robust measures of CVR using MRI. Multiple investigations examined blood flow changes, magnetic field effects, pharmacological interventions, and advanced CVR analysis methods.

Findings demonstrated that pCASL blood flow measurements showed significant parameter dependent variations during hypercapnic challenges, with notable regional CBF variation. Magnetic field investigations revealed modest B_0 changes during hyperventilation and optimal B_1 field characteristics at the V3 vertebral artery segment.

A pharmacological intervention study examined the effects of anti-hypertensive medication during hypercapnic challenges. This was to alter the blood pressure and see what affect it had on CVR. While these interventions induced expected heart rate changes, they did not significantly alter blood pressure or carotid artery blood flow, suggesting robust compensatory mechanisms in healthy individuals.

Advanced CVR measurement techniques were explored using multiple post labelling delay "enhanced" ASL (eASL) and blood oxygen level dependent (BOLD) MRI, with a novel semi-automated gas delivery box. The eASL data showed a substantial CVR response (~60\% increase in CBF, ~22 s decrease in arterial transit time) during hypercapnia, which was a larger change than recent studies. The dynamically modelled BOLD (dCVR) analysis of the haemodynamic response function showed a 3.2\% increase in magnitude. However, the processing was computationally intensive.

A study into the comparison of eASL, sinusoidal modelled BOLD CVR (sinCVR), and dCVR analyses showed no correlation between eASL and BOLD-based magnitude measures. There was a weak correlation between eASL and sinCVR timing metrics. sinCVR and dCVR magnitude were strongly positively correlated, whilst their timing metrics were weakly negatively correlated. This suggested the relationship between the different methods and physiology would require further investigation.

In conclusion, recent developments in acquisition and analysis of functional MRI were combined to resolve issues regarding CVR quantification. The intended impact was to improve the robustness of CVR results for diagnosis and prognosis of patients with cerebrovascular diseases.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Blockley, Nicholas P. Greenhaff, Paul L.
Keywords:	MRI, CVR, BOLD, pCASL, hypercapnic challenge, ASL
Subjects:	Q Science > QP Physiology > QP351 Neurophysiology and neuropsychology
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID:	81382
Depositing User:	Milbourn, Colette
Date Deposited:	24 Jul 2025 04:40
Last Modified:	24 Jul 2025 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/81382

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