Investigating the impact of early brain injury on outcomes after subarachnoid haemorrhage using MRI

Subarachnoid haemorrhage (SAH) is the commonest cause of stroke in young adults and is often fatal or results in serious disability. It occurs when small defects in the blood vessels of the brain rupture and despite successful treatment, patients who survive are still at risk of complications, of which the most serious is the development of secondary strokes. Currently, it is not known exactly why these secondary strokes occur and it is difficult to predict which patients are most at risk. Changes in the brain in the initial days after the bleed may predispose patients to developing these secondary strokes but currently, it is difficult to assess how much damage the bleed has done to brain tissue.
We plan to use specialised magnetic resonance imaging (MRI) techniques that do not require injections or radiation in healthy volunteers and patients. This will improve our knowledge of the causes of these secondary strokes, and assess whether MRI can be used to help predict which patients are most at risk. Results we obtain will also allow us to better evaluate existing treatments and hopefully lead to new treatment strategies in SAH, as well as other types of stroke.

Background: Delayed cerebral ischaemia (DCI) is the most important cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (SAH). Despite extensive research, the exact pathophysiology is still unclear and predicting, diagnosing and treating the condition remains difficult. Recent studies have highlighted the importance of the ischaemic damage caused by the initial bleed - so called early brain injury (EBI). This may result in a number of processes including cortical spreading depression, that damage resting state connectivity in the brain and result in neurocognitive deficits after SAH. The majority of current data following SAH has been obtained from animal studies with little in-vivo research and there is no current clinical method for assessing, treating or preventing either EBI or cortical spreading depression. Many patients may remain clinically asymptomatic despite significant cerebral injury and the impact of this on functional outcome is unknown.

Aims and Objectives:
1. To use magnetic resonance imaging (MRI) scanning techniques to assess and quantify the changes in cerebral perfusion, structure and function that occur due to EBI
2. To assess whether EBI causes damage to resting state cortical connectivity
3. To assess whether long term clinical and neuro-cognitive outcomes are linked to EBI
4. To assess the potential of MRI evidence of EBI to act as a tissue biomarker in predicting the risk of DCI after SAH

Study Design: The proposed project will have 3 component studies: 1) A healthy volunteer study into the effects of nimodipine on cerebral perfusion. 2) A prospective comparison study of MRI and clinical data from patients taken post-SAH with healthy controls. 3) A follow-up study of patients at 2 months post-SAH to correlate ischaemic damage at the time of the bleed with functional and neurocognitive outcomes.

Methodology: The MRI brain imaging protocol planned includes arterial spin labeling (ASL), vascular space occupancy (VASO) and blood oxygenation level dependent (BOLD) sequences, as well as structural imaging (T1,T2). Analysis of MRI data will include standard general linear modelling, perfusion analysis and independent component analysis. This will link multi-modal MRI data obtained acutely following SAH with long-term clinical and neurocognitive outcomes.

Opportunities: This research will investigate the role of functional MRI in the assessment of EBI after SAH and inform on the pathological processes in-vivo that remain unclear. It will also assess the impact of EBI on functional and neurocognitive outcomes following SAH and whether MRI can identify tissue biomarkers that predict risk of DCI.