Integrated functional characterisation in acute vascular syndromes: multimodal MRI / PET-CT imaging combined with leukocyte expression profiling

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Circulatory disease, such as heart attacks and strokes, remain the most common cause of death in the UK, contributing to almost one-third of all deaths registered in 2010. Each year, over 180,000 people die from circulatory disease in the UK alone, with 82,000 deaths from coronary heart disease and a further 49,000 from stroke. This costs the UK in excess of £30 billion each year due to healthcare associated costs and loss of workforce productivity. Despite this very substantial burden of disease, tools for identifying patients at high risk of acute vascular events remain extremely limited. As a consequence, a large proportion of events are unheralded. Even in patients with established disease, inability to distinguish patients at high and low risk means that optimal treatments cannot be targeted rationally and cost-effectively.It is well recognised that the final common events of arterial blockage in heart attack and strokes are often the results of arterial thrombosis (blood clots forming within arteries). Arterial thrombosis is commonly triggered by ruptured fatty deposits within the arterial wall known as atherosclerotic plaques. Despite considerable efforts in the past decade, no single imaging modality has succeeded in accurately identifying these high-risk, "vulnerable" plaques. The need for better plaque and patient characterisation has now become even more urgent and pressing, with a new generation of cardiovascular drugs near the clinical horizon, which directly target plaque behaviour and biology with no anticipated effect on plaque size and are therefore not detectable by conventional imaging techniques. The purpose of our proposed research is to use sophisticated, high-end laboratory techniques to first define the characteristics of plaque constituent cells from explanted human tissue following acute stroke. We can then relate this molecular "signature" to plaque imaging characteristic using state-of-the-art techniques with MRI, as well as PET nuclear imaging, which can detect plaques' biological activity. By combining imaging data and cellular analysis, we aim to evaluate the cellular events that drive plaque activity, and to generate a unique characterisation of patients at risk.We will develop a multimodal vascular imaging protocol with MRI/PET-CT in Oxford that can be validated at a cellular or molecular level within the plaque constituent cells. With our new research-dedicated Oxford Acute Vascular Imaging Centre (AVIC), and the strong tie between the University and the NHS, Oxford is strategically poised to lead research into the early phase of acute vascular syndromes. Through this innovative project, we hope to generate tools that will aid (1) diagnosis and risk stratification, (2) monitoring response to treatment (3) evaluation of new drugs and interventions - all of which reflect pressing current clinical unmet need.