Abstract
Brain areas exhibiting impaired cerebrovascular reserve are believed to be at higher risk of ischemic tissue injury under circumstances in which cerebral blood flow is insufficient to meet metabolic demand. Other than for acute ischemia, which results in apparent (irreversible) loss of brain tissue and function, the consequences of chronic
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intermittent hemodynamic failure are not well understood. In these instances, perfusion of brain tissue may be just sufficient to prevent gross ischemia but may fail to respond adequately to increases in demand such as those normally seen during neuronal activation. To date, there are no studies published on the anatomical and clinical consequences of non-ischemic chronic intermittent hypoperfusion in humans. However, experimental animal models simulating a state of non-ischemic chronic hypoperfusion show a decline in neuronal structure and viability. To investigate whether chronic hypoperfusion is present, the integrity of the cerebrovascular flow response system can be assessed by measures of cerebrovascular reactivity (CVR), a measure of the change in cerebral blood flow in response to a vasodilatory stimulus. Reductions in CVR can range from a blunted increase in blood flow in response to a stimulus in mild cases, to “paradoxical” reduction in regional blood flow indicating steal physiology, in severe cases. Existing imaging methods for spatially measuring cerebrovascular reserve, such as 133Xe-CT and Single Photon Emission Computed Tomography (SPECT), have drawbacks, including cost and limited clinical availability. In this thesis, I extensively use a non-invasive quantitative MR-based method to infer the anatomical and clinical consequences of impaired cerebrovascular reserve. This method employs functional acquisitions of blood oxygen-level dependent (BOLD) MR contrast with standardized iso-oxic changes in end-tidal PCO2 as the vasoactive stimulus. Specifically, I will investigate the adverse effects of chronically compromised blood flow control on the health of brain tissue to associate this with the onset of clinical symptoms in patients with severe chronic steno-occlusive cerebrovascular disease and brain arteriovenous malformations. Where MRI-CVR measurements require precise changes in end-tidal pCO2, I will also study the translation of the standardized PCO2 stimuli for patients that require mechanical ventilation (i.e. positive inspiratory pressure), using an animal model. This method may open up future research avenues for critically ill patients who may benefit from MRI-CVR studies, such as patients who suffer from traumatic brain injuries or a subarachnoid hemorrhage due to aneurysmal rupture
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