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.
J. Kevin DeMarco and John Huston III
Stephen P. Lownie and David M. Pelz
Waleed Brinjikji, John Huston III, Alejandro A. Rabinstein, Gyeong-Moon Kim, Amir Lerman and Giuseppe Lanzino
Carotid artery stenosis is a well-established risk factor of ischemic stroke, contributing to up to 10%-20% of strokes or transient ischemic attacks. Many clinical trials over the last 20 years have used measurements of carotid artery stenosis as a means to risk stratify patients. However, with improvements in vascular imaging techniques such as CT angiography and MR angiography, ultrasonography, and PET/CT, it is now possible to risk stratify patients, not just on the degree of carotid artery stenosis but also on how vulnerable the plaque is to rupture, resulting in ischemic stroke. These imaging techniques are ushering in an emerging paradigm shift that allows for risk stratifications based on the presence of imaging features such as intraplaque hemorrhage (IPH), plaque ulceration, plaque neovascularity, fibrous cap thickness, and presence of a lipid-rich necrotic core (LRNC). It is important for the neurosurgeon to be aware of these new imaging techniques that allow for improved patient risk stratification and outcomes. For example, a patient with a low-grade stenosis but an ulcerated plaque may benefit more from a revascularization procedure than a patient with a stable 70% asymptomatic stenosis with a thick fibrous cap.
This review summarizes the current state-of-the-art advances in carotid plaque imaging. Currently, MRI is the gold standard in carotid plaque imaging, with its high resolution and high sensitivity for identifying IPH, ulceration, LRNC, and inflammation. However, MRI is limited due to time constraints. CT also allows for high-resolution imaging and can accurately detect ulceration and calcification, but cannot reliably differentiate LRNC from IPH. PET/CT is an effective technique to identify active inflammation within the plaque, but it does not allow for assessment of anatomy, ulceration, IPH, or LRNC. Ultrasonography, with the aid of contrast enhancement, is a cost-effective technique to assess plaque morphology and characteristics, but it is limited in sensitivity and specificity for detecting LRNC, plaque hemorrhage, and ulceration compared with MRI.
Also summarized is how these advanced imaging techniques are being used in clinical practice to risk stratify patients with low- and high-grade carotid artery stenosis. For example, identification of IPH on MRI in patients with low-grade carotid artery stenosis is a risk factor for failure of medical therapy, and studies have shown that such patients may fair better with carotid endarterectomy (CEA). MR plaque imaging has also been found to be useful in identifying revascularization candidates who would be better candidates for CEA than carotid artery stenting (CAS), as high intraplaque signal on time of flight imaging is associated with vulnerable plaque and increased rates of adverse events in patients undergoing CAS but not CEA.
Kelly B. Mahaney, Robert D. Brown Jr., Irene Meissner, David G. Piepgras, John Huston III, Jie Zhang and James C. Torner
The aim of this study was to determine age-related differences in short-term (1-year) outcomes in patients with unruptured intracranial aneurysms (UIAs).
Four thousand fifty-nine patients prospectively enrolled in the International Study of Unruptured Intracranial Aneurysms were categorized into 3 groups by age at enrollment: < 50, 50–65, and > 65 years old. Outcomes assessed at 1 year included aneurysm rupture rates, combined morbidity and mortality from aneurysm procedure or hemorrhage, and all-cause mortality. Periprocedural morbidity, in-hospital morbidity, and poor neurological outcome on discharge (Rankin scale score of 3 or greater) were assessed in surgically and endovascularly treated groups. Univariate and multivariate associations of each outcome with age were tested.
The risk of aneurysmal hemorrhage did not increase significantly with age. Procedural and in-hospital morbidity and mortality increased with age in patients treated with surgery, but remained relatively constant with increasing age with endovascular treatment. Poor neurological outcome from aneurysm- or procedure-related morbidity and mortality did not differ between management groups for patients 65 years old and younger, but was significantly higher in the surgical group for patients older than 65 years: 19.0% (95% confidence interval [CI] 13.9%–24.4%), compared with 8.0% (95% CI 2.3%–13.6%) in the endovascular group and 4.2% (95% CI 2.3%–6.2%) in the observation group. All-cause mortality increased steadily with increasing age, but differed between treatment groups only in patients < 50 years of age, with the surgical group showing a survival advantage at 1 year.
Surgical treatment of UIAs appears to be safe, prevents 1-year hemorrhage, and may confer a survival benefit in patients < 50 years of age. However, surgery poses a significant risk of morbidity and death in patients > 65 years of age. Risk of endovascular treatment does not appear to increase with age. Risks and benefits of treatment in older patients should be carefully considered, and if treatment is deemed necessary for patients older than 65 years, endovascular treatment may be the best option.