Abstract and Introduction
Abstract
In this paper, the authors review the definition of high-risk plaque as developed by experienced researchers in atherosclerosis, including pathologists, clinicians, molecular biologists, and imaging scientists. Current concepts of vulnerable plaque are based on histological studies of coronary and carotid artery plaque as well as natural history studies and include the presence of a lipid-rich necrotic core with an overlying thin fibrous cap, plaque inflammation, fissured plaque, and intraplaque hemorrhage. The extension of these histologically identified high-risk carotid plaque features to human in vivo MRI is reviewed as well. The authors also assess the ability of in vivo MRI to depict these vulnerable carotid plaque features. Next, the ability of these MRI-demonstrated high-risk carotid plaque features to predict the risk of ipsilateral carotid thromboembolic events is reviewed and compared with the risk assessment provided by simple carotid artery stenosis measurements. Lastly, future directions of high-risk carotid plaque MRI are discussed, including the potential for increased clinical availability and more automated analysis of carotid plaque MRI. The ultimate goal of high-risk plaque imaging is to design and run future multicenter trials using carotid plaque MRI to guide individual patient selection and decisions about optimal atherosclerotic treatment strategies.
Introduction
Stroke remains a leading cause of morbidity and mortality. Treatment decisions are still based predominantly on studies correlating the risk reduction achieved from carotid endarterectomy (CEA) or carotid artery stenting (CAS) with the percentage of stenosis. While the benefit of CEA in recently symptomatic carotid artery stenosis > 70% has been demonstrated in multiple large randomized clinical trials, the role of surgical versus medical treatment in symptomatic patients with less significant carotid stenosis remains unclear. The benefit of CEA or CAS is even more controversial in patients with asymptomatic carotid stenosis. The Asymptomatic Carotid Atherosclerosis Study (ACAS) has reported a risk reduction following CEA in asymptomatic patients with stenosis greater than 50%–60%. Since completion of the ACAS trial, there have been significant advances in medical therapy for carotid atherosclerotic disease. The average annual rate of ipsilateral stroke in patients with asymptomatic carotid stenosis receiving medical therapy since 2001 has fallen below the rates in patients who underwent CEA in the ACAS. In a systematic review and analysis of medical intervention, Abbott concluded that current medical intervention alone is now best for stroke prevention in part because high-risk patients who may benefit from additional CEA cannot be identified. The lack of a clear benefit from surgical versus medical therapy in symptomatic patients with < 70% stenosis or in patients with asymptomatic carotid stenosis suggests that better characterization of future stroke risk is necessary to identify which patients will benefit the most from CEA or CAS. Unfortunately, current risk stratification based on the percentage of stenosis provides minimal patient-specific information on the actual risk of stroke for most individuals with carotid artery disease. A growing body of literature suggests that carotid plaque characteristics may provide a superior means of predicting future ipsilateral cerebrovascular events as compared with the percentage of carotid artery stenosis.