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Imaging of High-Risk Carotid Artery Plaques: Current Status and Future Directions

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Imaging of High-Risk Carotid Artery Plaques: Current Status and Future Directions Neurosurg Focus 36 (1):E1, 2014 ©AANS, 2014 Imaging of high-risk carotid artery plaques: current status and future directions J. KEVIN DEMARCO, M.D.,1 AND JOHN HUSTON III, M.D.2 1Department of Radiology, Michigan State University, East Lansing, Michigan; and 2Department of Radiology, Mayo Clinic, Rochester, Minnesota 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 pro- vided 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. (http://thejns.org/doi/abs/10.3171/2013.10.FOCUS13384) KEY WORDS • carotid stenosis • stroke • carotid plaque • MRI TROKE remains a leading cause of morbidity and current medical intervention alone is now best for stroke mortality. Treatment decisions are still based pre- prevention in part because high-risk patients who may dominantly on studies correlating the risk reduction benefit from additional CEA cannot be identified.1 The Sachieved from carotid endarterectomy (CEA) or carotid lack of a clear benefit from surgical versus medical ther- artery stenting (CAS) with the percentage of stenosis. apy in symptomatic patients with < 70% stenosis or in While the benefit of CEA in recently symptomatic carotid patients with asymptomatic carotid stenosis suggests that artery stenosis > 70% has been demonstrated in multiple better characterization of future stroke risk is necessary large randomized clinical trials, the role of surgical ver- to identify which patients will benefit the most from CEA sus medical treatment in symptomatic patients with less or CAS. Unfortunately, current risk stratification based significant carotid stenosis remains unclear.3 The benefit on the percentage of stenosis provides minimal patient- of CEA or CAS is even more controversial in patients specific information on the actual risk of stroke for most with asymptomatic carotid stenosis. The Asymptomatic individuals with carotid artery disease. A growing body Carotid Atherosclerosis Study (ACAS) has reported a of literature suggests that carotid plaque characteristics risk reduction following CEA in asymptomatic patients may provide a superior means of predicting future ipsi- with stenosis greater than 50%–60%.34 Since completion lateral cerebrovascular events as compared with the per- of the ACAS trial, there have been significant advances in centage of carotid artery stenosis. medical therapy for carotid atherosclerotic disease. The average annual rate of ipsilateral stroke in patients with asymptomatic carotid stenosis receiving medical therapy Correlating the American Heart Association since 2001 has fallen below the rates in patients who un- Carotid Plaque Classification With Plaque MRI derwent CEA in the ACAS.1 In a systematic review and analysis of medical intervention, Abbott concluded that Definition of Vulnerable Plaque Histological studies have demonstrated that coro- Abbreviations used in this paper: ACAS = Asymptomatic Carotid nary artery plaques with a large lipid-rich necrotic core Atherosclerosis Study; AHA = American Heart Association; CAS (LRNC) and an overlying thin fibrous cap (FC) are as- = carotid artery stenting; CE = contrast-enhanced; CEA = carotid 31 endarterectomy; FC = fibrous cap; IPH = intraplaque hemorrhage; sociated with sudden cardiac death. This finding has led LRNC = lipid-rich necrotic core; MRA = MR angiography; SNR to the concept of “vulnerable plaque.” Key features of the = signal-to-noise ratio; T1W = T1-weighted; T2W = T2-weighted; vulnerable plaque, including a large LRNC with a thin FC, TIA = transient ischemic attack; TOF = time-of-flight. active inflammation with activated macrophages, fissured Neurosurg Focus / Volume 36 / January 2014 1 Unauthenticated | Downloaded 10/02/21 04:47 AM UTC J. K. DeMarco and J. Huston III plaque, superficial calcified nodules, and intraplaque Plaque Inflammation hemorrhage (IPH), were defined in two consensus review Observational studies on LRNC demonstrate that articles published by a group of experienced researchers neo-angiogenesis is closely associated with plaque pro- in atherosclerosis, including pathologists, clinicians, mo- 33 15,16 gression. Intimal neovascularization is predominantly lecular biologists, and imaging scientists. The discus- thought to arise from the adventitia, where there are a sion of pathological definitions of vulnerable plaque was 22 plethora of preexisting vasa vasorum. The amount of ad- subsequently extended to MRI. The American Heart ventitial neovascularity can be quantified using dynamic Association (AHA) has proposed a detailed classification contrast-enhanced (DCE) MRI. Histological evaluation scheme of atherosclerotic plaque (Fig. 1).26 This scheme showed that adventitial Ktrans calculated from DCE-MRI has been modified for in vivo MRI to include the descrip- was significantly correlated with the amount of neovascu- tion of carotid plaques with LRNCs (AHA Type IV–V) as well as a more complex plaque with IPH, ruptured FC, larity and macrophages in the excised plaque, thus provid- and/or calcified protruding nodule (AHA Type VI).5 ing an in vivo marker of plaque inflammation, which has been described as a hallmark of the vulnerable plaque.11 Lipid-Rich Necrotic Core With Thin FC Fissured Plaque Based on the histological studies of coronary artery plaque associated with sudden cardiac death, an LRNC Virmani et al. described the fissure plaque as a region of FC rupture where the juxtaluminal thrombus was in di- has also been proposed to represent a phenotype of ath- 32 erosclerotic disease with a high risk for future cardiovas- rect communication with the underlying LRNC. Using cular events.29 The most widely accepted hypothesis is either noncontrast 3D time-of-flight (TOF) MR angiog- that lipid-lowering therapy targets the plaque rupture risk raphy (MRA) or a CE-T1W MRI series, multiple authors features such as a large LRNC, thin FC, and high level have demonstrated the ability of in vivo carotid plaque of inflammatory infiltrates and activity. The lipid deple- MRI to differentiate between a thick, intact FC and a thin tion theory suggests that plaque stability is improved and or ruptured FC. Using 3D TOF MRA, Hatsukami et al. demonstrated a high level of agreement (89%) between cardiovascular events are reduced with medical treatment 9 such as statin therapy to deplete lipids and decrease the MRI and histological findings. Cai et al. used CE-T1W LRNC size.37 Multicontrast MRI of the carotid arteries MRI series to optimally demonstrate the FC and showed has been validated with histology and shown to identify moderate-to-good correlation between carotid MRI find- and quantify various carotid plaque components includ- ings and the excised histological specimen for maximal 4,21 thickness (r = 0.78, p < 0.001), length (r = 0.73, p < 0.001), ing the LRNC, FC, and IPH (Fig. 2). Contrast-enhanced 4 (CE) T1-weighted (T1W) images improve differentiation and area (r = 0.90, p < 0.001) of the intact FC. 36 of the LRNC from fibrous tissue. Further, multicontrast Intraplaque Hemorrhage carotid plaque MRI has been shown to be capable of quantifying the LRNC volume in the clinical setting of a The cause of IPH is unclear. Some authors have sug- multicenter trial with low interscan variability.24 gested that hemorrhage into a plaque is related to rupture FIG. 1. Different types of vulnerable plaque as the underlying cause of acute coronary events and sudden cardiac death. A, rupture-prone plaque with a large lipid core and thin FC infiltrated by macrophages; B, ruptured plaque with subocclusive throm- bus and early organization; C, erosion-prone plaque with proteoglycan matrix in a smooth muscle cell–rich plaque; D, eroded plaque with subocclusive thrombus; E, IPH due to leaking vasa vasorum; F, calcific nodule protruding into the vessel lumen; G, chronically stenotic plaque with severe calcification, old thrombus, and eccentric lumen. Reprinted with permission from Naghavi M et al: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 108:1772–1778, 2003. 2 Neurosurg Focus / Volume 36 / January 2014 Unauthenticated | Downloaded 10/02/21 04:47 AM UTC Imaging of high-risk carotid plaques FIG. 2. Comparison of high-resolution MR angiography (MRA), multicontrast 3-T in vivo carotid plaque MRI, and ex
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