Imaging of high-risk carotid plaques: ultrasound

https://doi.org/10.1053/j.semvascsurg.2017.04.010Get rights and content

Abstract

Duplex ultrasonography has a well-established role in the assessment of the degree of stenosis caused by carotid atherosclerosis. This assessment is derived from Doppler velocity changes induced by the narrowing lumen of the artery. New research into the mechanisms for plaque rupture and atheroembolic stroke indicates that the degree of narrowing is an imperfect predictor of stroke risk, and that other factors, such as plaque composition and remodeling and biomechanical forces acting on the plaque, can play a role. New advances in ultrasound imaging technology have made it possible to investigate these measures of plaque vulnerability to identify pre-embolic unstable carotid plaques. Efforts have been made to quantify the morphologic appearance of the plaque in B-mode images and to correlate them with histology. Additional research has resulted in the first generation of clinically available 3-dimensional ultrasound transducers that reduce operator-dependence and variability. Finally, ultrasonography provides real-time imaging and physiologic information that can be utilized to measure disruptive forces acting on carotid plaques. We review some of these exciting developments in ultrasonography and discuss how these may impact clinical practice.

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

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