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Title: Using magnetic resonance imaging to investigate early brain injury after aneurysmal subarachnoid haemorrhage
Author: Rowland, Matthew James
ISNI:       0000 0004 6352 7483
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Aneurysmal subarachnoid haemorrhage (SAH) is a devastating disease frequently leading to death or poor functional outcome and the pathophysiological changes that occur acutely post-rupture remain poorly understood. The work presented here describes a series of studies correlating serial magnetic resonance imaging (MRI) scanning and bedside saccadometry with neurocognitive outcomes to investigate early brain injury after SAH. Further experiments investigate the potential of saccadometry as a bedside biomarker of cerebral ischaemia post-rupture and use MRI in a model of cerebral hypoxia to explore the mechanisms underlying the therapeutic effects of nimodipine. Firstly, results demonstrated significantly increased apparent grey matter volume and restricted diffusion in the first 72 hours post-SAH in patients, suggesting the presence of undiagnosed and significant global cerebral oedema. Furthermore, structural images acquired at this stage enabled us to predict with high accuracy and specificity which patients will develop poor neurocognitive outcomes at three months. Next we investigated the impact of early brain injury on functional connectivity after SAH. Patients showed significantly increased functional connectivity compared to healthy controls in a number of functional networks associated with complex cognitive or emotional functions at all timepoints post-SAH. Neurocognitive impairment was associated with increased and decreases in functional connectivity and all differences were independent from any effect of altered grey matter volume. Improving the prediction of which patients are most at risk of developing secondary ischaemia following SAH remains a key area for research focus. We therefore used a portable beside saccadometer to acquire serial measurements of eye movements acutely post-rupture with results demonstrating faster eye movements are correlated with higher cerebral blood flow in the first 72 hours post-SAH. Finally, we used MRI to quantify the changes in cerebral structure, perfusion and function associated with a healthy volunteer model of acute hypoxia, and the effect of calcium channel blockade with nimodipine on these changes. Results suggest a preferential effect of calcium channel blockade in reversing regional MRI changes under conditions of hypoxia. These changes may help explain the outcome benefit seen in aneurysmal subarachnoid haemorrhage. This thesis highlights the potential of MRI imaging to offer biomarkers of early brain injury in the acute period post-SAH, to improve prediction of patients most at risk of neurocognitive impairment and to offer new insight into the mechanisms behind the therapeutic benefit seen with nimodipine.
Supervisor: Pattinson, Kyle ; Jezzard, Peter Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available