Development and application of perfusion MRI methods Innovating the measurement of cerebrovascular physiology

A healthy cerebrovasculature is important in maintaining constant delivery of blood carrying oxygen and nutrients required for normal cerebral function. There is a considerable body of research into the regulation of the cerebrovasculature and cerebral blood flow, which has improved diagnosis, treatment and prevention of cerebrovascular pathology. However, a severe confound in research concerning the cerebrovasculature is the limited amount of in vivo human data available that assesses function and physiology of key cerebral structures: the brainstem and the cerebral arteries themselves. The work presented in this thesis aims to provide non-invasive imaging tools that can be used to further the understanding of cerebrovascular function and physiology. Herein, innovations of arterial spin labelling, an established magnetic resonance imaging technique to measure perfusion, are presented that address the challenges of measuring brainstem cerebrovascular physiology and facilitate a novel measurement of cerebral arterial compliance, a marker of cerebrovascular health. Regulation of the cerebrovasculature by the sympathetic nervous system is used throughout this thesis as an example process that can be investigated with arterial spin labelling based imaging methods, because the brainstem is an important sympathetic control centre and changes in sympathetic outflow directly affect the cerebral arteries. Firstly, arterial spin labelling is adapted to measure cerebral blood flow in the brainstem. The arterial spin labelling method tailored for the brainstem is then applied in the investigation of cerebral blood flow in the presence of poly-cystic ovary syndrome, a pathology recently associated with elevated sympathetic outflow. Secondly, an arterial spin labelling based approach to measure cerebral arterial compliance is introduced. Lastly, this thesis shows that a combination of the optimised brainstem perfusion imaging method and the novel arterial compliance measurement is able to investigate clinically relevant processes, including cerebral autoregulation and Cushing’s mechanism