Imaging of high-risk carotid plaques: ultrasound
Introduction
Approximately 20% to 30% of ischemic strokes are caused by debris originating from rupturing carotid artery plaques [1]. Currently, the percent diameter reduction in the carotid arteries is used as an indication for stroke risk. The risk factors that lead to plaque rupture, however, remain incompletely understood. Stroke rates achieved after carotid endarterectomy (CEA) for high-grade carotid stenosis are significantly lower than those observed with best medical therapy alone [2]. A majority of medically treated patients, however, remain stroke-free during follow-up. Increasing degrees of stenosis have not been associated with a correspondingly increased risk for stroke in asymptomatic patients [3]. It is therefore important to identify additional markers to assess the risk of stroke and to identify patients who would benefit most from revascularization. Several potential markers of vulnerable plaques have been proposed. These include plaque volume, lipid necrotic core size, surface ulceration, intraplaque hemorrhage, as well as hemodynamic effects around the plaque [4].
Magnetic resonance imaging is a sensitive and specific method for determining the plaque characteristics [5], [6]. Computed tomography angiography is, at present, not as accurate in delineating plaque composition. It is, however, useful for identifying the luminal surface outline [7], [8]. On the other hand, duplex ultrasonography is the most widely available and low-risk noninvasive test to assess carotid plaque severity, although its correlation with angiographically-measured stenosis severity is low [9]. Two-dimensional (2D) B-mode imaging can visualize a number of anatomic features of the arterial wall and plaque. While image quality of ultrasound and the observable anatomic detail continues to improve, it is still limited by observer variability. The addition of 3-dimensional (3D) imaging protocols has attempted to address that limitation [10]. An important strength of ultrasonography is its ability to provide real-time physiologic information on blood flow and vessel wall/plaque motion. There is still no single modality that can be totally relied upon as the only imaging study in differentiating between the stable and unstable plaques [11].
Noninvasive imaging (magnetic resonance imaging, computed tomography angiography, or duplex ultrasonography) can now define the appearance of symptomatic ruptured plaques. However, this has not translated into major changes in clinical practice, despite significant research efforts in sophisticated, well-designed plaque studies. This is because the noninvasive morphologic features of pre-embolic unstable plaques and their correlation with stroke still remain ill-defined due to a low incidence of stroke in asymptomatic patients with carotid plaques. Therefore, there continues to be a need to develop and validate plaque features that will identify patients at risk for future plaque disruption and atheroembolic cerebral infarction.
Animal studies indicate that enlarging lipid cores, increasing intraplaque hemorrhage, and fibrous cap thinning predispose plaques to rupture, and could serve as noninvasive markers of plaque instability. However, these features form a continuum. The exact threshold value of lipid core size, for example, that marks the onset of instability is not known. Identification of these values would require a serial analysis of plaque changes over time, and correlation of these changes with atheroembolization and any developing clinical events. Importantly, atheromas can evolve, regress, enlarge, or undergo structural change over periods of time as brief as 6 months [12]. Therefore one-time imaging cannot assess the long-term biologic behavior of a plaque, and no longitudinal studies have been performed to define noninvasive morphological markers of plaque instability.
In this review, we present a summary of the current role of ultrasonography is assessing carotid atherosclerotic disease, and ongoing research that may expand its role to include more sophisticated risk stratification based on structural and biomechanical characteristics.
Section snippets
B-mode imaging
B-mode (brightness mode or 2D mode) imaging displays anatomic wall features, which can range from primarily hyper- or hypo-echoic to heterogeneous in echogenicity. Because different tissues reflect ultrasound to varying degrees, the first attempt to provide a meaningful description of the variety of B-mode appearances of carotid plaques included a visual impression: pure hypoechoic (type I), hypoechoic with small hyperechoic areas (type II), hyperechoic with small hypoechoic areas (type III),
Pixel distribution analysis
Atherosclerotic plaques originate from fatty streaks that, over time, coalesce into a lipid core. Fibroatheromas form as fibrous tissue accumulates over the core and forms a fibrous cap. The notion of an unstable or vulnerable atherosclerotic plaque was first proposed for the coronary artery based on the observation that all coronary culprit lesions were not necessarily high-grade stenoses. Emerging information indicates that fibroatheromas are rendered unstable or vulnerable through an
3D ultrasonography
Plaques progress along the vessel 2.4 times faster than they thicken [21]. Therefore, methods that capture both longitudinal and circumferential growth (ie, area and volume) are inherently more sensitive than methods limited to thickness measurements (ie, diameter-reducing stenosis). The 5-year risk of stroke, myocardial infarction, and vascular death is 19% for plaques with a longitudinal-sectional area of 1.2 to 6.7 cm2 compared to 6% for areas of 0 to 0.1 cm2. Therefore, plaque area and
Contrast-enhanced ultrasonography
Contrast-enhanced ultrasound (CEUS) uses standard B-mode imaging combined with the administration of an intravenous ultrasonographic contrast agent. This improves the quality of images with a better delineation of structures where the contrast can reach. It has traditionally been used in cardiac echocardiography, and its use is now being explored in carotid ultrasonography. Ultrasound contrast consists of microbubbles of an inert gas. The gas can be stabilized by providing a phospholipid shell.
Plaque strain measurement
In addition to the structure and composition of the atherosclerotic plaque, the biomechanical forces acting on the plaque have also been hypothesized to play a role in increasing the risk of rupture. Biomechanical factors include the hemodynamic forces acting on the plaque, as well as the viscoelastic mechanical properties of the plaque components. Ultrasound elastography or strain imaging is a method for visualizing and quantifying the deformation that tissues undergo in response to an
IVUS
Information about morphologic characteristics of a carotid plaque may be important at the time of carotid intervention. For example, the manipulation of a soft plaque can potentially provoke embolization and stroke or a very stiff plaque could prevent stent expansion with consequent residual stenosis after CAS. Periprocedural stroke has been more frequently associated with CAS and therefore, every attempt should be made to reduce embolization during CAS. IVUS has been used in the coronary
Conclusions
The estimation of degree of stenosis based on Doppler velocity measurements is the most well-established role of ultrasonography in the diagnostic workup of carotid artery atherosclerotic disease. There is, however, a clinical imperative to obtain additional information on the plaque. Characteristics of the plaque, such as volume, lipid necrotic core size and location, surface ulceration, intraplaque hemorrhage, as well as hemodynamic effects around the plaque have been associated with an
References (54)
Quantifying atherosclerosis by 3D ultrasound works!: But there is work to be done
J Am Coll Cardiol
(2015)- et al.
Non-invasive carotid artery imaging to identify the vulnerable plaque: current status and future goals
Eur J Vasc Endovasc Surg
(2015) - et al.
The identification of the high risk carotid plaque
Eur J Vasc Endovasc Surg
(1996) - et al.
Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis
J Vasc Surg
(1997) - et al.
Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques
J Vasc Surg
(2002) - et al.
Noninvasive identification of the unstable carotid plaque
Ann Vasc Surg
(2006) - et al.
Carotid artery stenting: analysis of data for 105 patients at high risk
J Vasc Surg
(2003) - et al.
Carotid plaque morphometric assessment with three-dimensional ultrasound imaging
J Vasc Surg
(2015) - et al.
Usefulness of contrast-enhanced ultrasound for detection of carotid plaque ulceration in patients with symptomatic carotid atherosclerosis
Am J Cardiol
(2013) - et al.
Effect of carotid plaque screening using contrast-enhanced ultrasound on cardiovascular risk stratification
Am J Cardiol
(2013)
Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries. correlation with histology and plaque echogenicity
J Am Coll Cardiol
Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques
JACC Cardiovasc Imaging
Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells
Ultrasound Med Biol
Carotid artery wall motion estimated from b-mode ultrasound using region tracking and block matching
Ultrasound Med Biol
Non-invasive in vivo characterization of human carotid plaques with acoustic radiation force impulse ultrasound: comparison with histology after endarterectomy
Ultrasound Med Biol
Ultrasound speckle tracking strain estimation of in vivo carotid artery plaque with in vitro sonomicrometry validation
Ultrasound Med Biol
Quantification of carotid plaque elasticity and intraplaque neovascularization using contrast-enhanced ultrasound and image registration-based elastography
Ultrasonics
Ultrasound-based carotid elastography for detection of vulnerable atherosclerotic plaques validated by magnetic resonance imaging
Ultrasound Med Biol
Intravascular ultrasound as a clinical adjunct for carotid plaque characterization
J Vasc Surg
Carotid plaque morphometric assessment with three dimensional ultrasound imaging
J Vasc Surg
Ischemic stroke subtypes: a population-based study of incidence and risk factors
Stroke
Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
JAMA
Risk of stroke in the distribution of an asymptomatic carotid artery. The European Carotid Surgery Trialists Collaborative Group
Lancet
Symptomatic and asymptomatic carotid artery plaque
Expert Rev Cardiovasc Ther
In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology
Circulation
Quantitative evaluation of carotid plaque composition by in vivo MRI
Arter Thromb Vasc Biol
Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA
Neurology
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