Title: Neurovascular imaging in patients with carotid artery disease to define high and low risk of stroke
Funder: Department of Health (England)

Abstract: Background Stroke is the third most common cause of death in England and has the largest disability impact of any chronic disease with an associated huge economic burden. Carotid endarterectomy substantially reduces the risk of stroke in patients with severe symptomatic carotid stenosis. However for lesser degrees of stenosis, the benefit of recanalisation is marginal and may be nulled by higher surgical or relatively low baseline risk. Knowledge of an individual’s risk of stroke is therefore needed to target treatment to those most likely to benefit. Non invasive imaging markers are available that predict the thromboembolic risk of carotid plaques and probe the haemodynamic reserve capacity. There is preliminnary and indirect evidence that these markers predict stroke. Aims In previous studies we and other groups have shown that intraplaque haemorrhage (IPH) predicts cerebrovascular events in patients with carotid disease. Specifically, IPH predicts (i) short-term recurrent ischaemic events in patients with symptomatic severe carotid stenosis, (ii) recurrent events over two years in patients with symptomatic mild and moderate carotid stenosis, and (iii) future cerebrovascular events in patients with asymptomatic carotid stenosis. The main aim of this study is to assess whether IPH detected by MRI can predict recurrent cerebral infarction in patients with symptomatic moderate degree stenosis. The secondary aim is to assess whether the cerebrovascular reserve capacity assessed by fMRI improves this prediction. Plan of Investigation Patients with symptomatic moderate degree carotid stenosis (50%+ according to NASCET assimilated ultrasound criteria) not undergoing CEA and on best medical treatment will be recruited after informed consent. All patients will undergo one baseline MR session (high resolution MR angiography, plaque imaging and cerebrovascular mapping), and then followed up with regular clinical visits until stroke or for up to 3 years. Interim diffusion MRI will be done when symptoms occur to identify infarction. Previously established methods will be used to assess the presence of IPH and to quantify vasoreactivity. Multivariate COX regression analysis will be performed to assess the effect of IPH, VMR and degree of stenosis on confirmed cerebrovascular events. Potential Impact Over 130,000 strokes a year cause a considerable burden for the UK, with the cost of ischaemic stroke estimated at £50,000. Carotid endarterectomy reduces the risk of stroke, but the benefit for those with moderate degree of stenosis is felt to be marginal with 22 CEA required to prevent 1 stroke. There is a need to consider patient related factors that are likely to increase or decrease the risk of stroke to effectively guide treatment. Identification of low and high risk subgroups could improve management by preventing natural strokes in a high risk groups and surgical risk in low risk groups. The study will test whether predefined MRI criteria allow identification of low and high risk groups. If confirmed, this work can be used to support clinical decision making.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE;CARDIOVASCULAR