Carotid-artery imaging in the diagnosis and management of patients at risk of stroke

Summary

Carotid atherosclerotic disease is one of the major preventable causes of ischaemic strokes. In clinical practice, decision making with regard to carotid endarterectomy or stenting is still primarily based on the extent of luminal stenosis. In most centres worldwide, luminal stenosis is now mainly assessed with non-invasive techniques, such as Doppler ultrasound, magnetic resonance angiography, and CT angiography, either alone or in combination. Although intra-arterial digital subtraction angiography remains the historical gold standard, it has now mostly been replaced by these non-invasive techniques. Moreover, in addition to luminal stenosis, certain morphological features of carotid plaques, such as large lipid cores, intraplaque haemorrhage, or thin or ruptured fibrous caps, are increasingly believed to be associated with heightened risk of stroke. In this Review, we discuss current state-of-the-art non-invasive diagnostic imaging strategies for luminal stenosis and describe the most promising novel imaging techniques, such as high-resolution MRI and CT combined with PET imaging, which can be used to characterise vulnerable carotid-plaque features in vivo.

Introduction

Stroke is the second most common cause of death in developed countries, causing 4·5 million deaths every year.¹ Stroke is also a major source of morbidity and long-term disability, resulting in substantial economic burden on health and social services worldwide. Despite advances in medical therapies and thrombolysis, effective stroke treatment remains elusive, in general terms, for various practical reasons. Therefore, prevention of stroke is still a paramount issue.

Up to 15% of cerebral infarctions are estimated to be associated with embolic debris and thrombi originating from atherosclerotic plaques at the carotid bifurcation.² The risk of stroke in patients with carotid atherosclerosis is closely associated with the severity of luminal stenosis. For asymptomatic patients with less than 75% stenosis, the yearly risk of stroke is less than 1%, but this risk increases to 2–5% for patients with stenosis greater than 75%.3, 4, 5 The risk is much higher in symptomatic patients (ie, those who have had previous transient ischaemic attacks or strokes) at 10% in the first year for those with severe lesions, with risk rising to 30–35% over the next 5 years.⁶ There is much clinical interest in carotid atherosclerotic disease because it is one of the major potentially preventable causes of stroke. Three pivotal studies (NASCET [the North American Symptomatic Carotid Endarterectomy Trial], ECST [the European Carotid Surgery Trial], and the Veteran Affairs Cooperative Studies Program Trial) have clearly shown the benefits of carotid endarterectomy compared with medical treatment in recently symptomatic patients with severe carotid stenosis.7, 8, 9 The pooled analysis of these three trials showed significant benefits of surgery in the group with severe stenosis (70–99% stenosis in NASCET; absolute risk reduction of 16%, p<0·001) after 5 years of follow-up.¹⁰ This finding equates to a net prevention of about one stroke after operating on six patients with severe carotid stenosis.¹⁰ In patients with mild stenosis (50% or less in NASCET), the risks incurred during carotid endarterectomy outweighed the benefits of surgery.¹⁰ Patients with moderate stenosis (50–69% in NASCET) still benefited from surgery, although the overall gains were more modest than in patients with severe stenosis, with an absolute risk reduction of 4·6% after 5 years.¹⁰ With improvements in technology such as distal protection devices and low-profile self-expanding stents, carotid angioplasty and stenting has emerged as a viable alternative to carotid endarterectomy. However, the role of stenting outside clinical trials remains uncertain and is, at present, recommended only in patients at high risk for surgical complications.¹¹

In asymptomatic carotid-artery disease, the efficacy of carotid endarterectomy is also poorly defined. Although several groups have reported no benefits from surgery,12, 13, 14 results from ACAS (Asymptomatic Carotid Atherosclerosis Study) showed that surgery for patients with stenosis greater than 60% resulted in a 5-year ipsilateral stroke rate of 11%, whereas optimum medical treatment (daily aspirin and medical risk factor management) resulted in a stroke rate of 5·1%.15, 16 The UK Medical Research Council ACST (Asymptomatic Carotid Surgery Trial) Collaborative Group confirmed a modest benefit of carotid endarterectomy in asymptomatic patients who were younger than 75 years and who had at least 70% carotid stenosis on ultrasound: immediate carotid endarterectomy halved the net 5-year stroke risk from about 12% to about 6%.¹⁷ Despite the modest benefit, there is an increasing trend to operate on asymptomatic patients, both in North America and Europe.¹⁸

There is a growing body of evidence from observational and epidemiological studies that the risk of subsequent stroke in patients with carotid stenosis is highest in the first few weeks after onset of transient ischaemic attacks or minor strokes, and this risk declines rapidly thereafter.19, 20, 21 This finding implies a short time window for effective stroke prevention, necessitating the rapid identification of patients with substantial carotid stenosis and the swift initiation of medical treatment or revascularisation procedures. The mainstay of carotid imaging is, therefore, not only to enable accurate grading of the severity of stenosis, but also to facilitate delivery of treatment within this short time window.

In this Review, we discuss current state-of-the-art non-invasive diagnostic imaging strategies for luminal stenosis. We also briefly describe novel and promising plaque imaging techniques that can be used to characterise vulnerable carotid-plaque features in vivo and can provide additional information to that obtained with luminal stenosis alone.