Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis?

Abstract

An atherosclerotic plaque requires a nutrient blood supply, which is predominantly derived from arterial vasa vasorum. A variety of factors (environmental and genetic) contribute to the initiation and growth of atherosclerosis within vessel walls. Chemotactic factors, such as tissue ischemic and hypoxic factors, stimulate the release of vascular endothelial growth factor (VEGF) proteins, resulting in vessel wall angiogenesis. These developments often precede the formation of the luminal plaque. In this report, we describe the use of contrast-enhanced carotid ultrasound (CECU) imaging for the detection and quantification of intra-plaque neovascularization. The efficacy of CECU was measured against the neovascular density observed within the tissue specimens obtained at the time of carotid endarterectomy surgery. The objective of this study was to provide a histologic correlation between CECU and carotid artery atherosclerotic plaque neovascularization. Fifteen patients with significant atherosclerotic carotid artery disease received a CECU examination prior to undergoing a carotid endarterectomy (CEA). Two patients received bilateral endarterectomies, resulting in a total of 17 cases. At the time of surgery, carotid plaque samples were surgically removed and stained with specific vascular markers (CD31, CD34, von Willebrand factor, and hemosiderin) designed to identify the presence and degree of neovascularization. The intra-plaque neovascularization recorded on preoperative CECU was correlated with the degree of neovascularization noted in the tissue specimens. The CECU neovascularization was correlated to CD31-stained tissue specimens. This correlation value was 0.68 using Spearman's rank method. When CECU results were correlated with the other histologic markers (CD34, von Willebrand factor, and hemosiderin), a correlation of 0.50 was obtained. In conclusion, contrast-enhanced carotid ultrasound correlated to the presence and degree of intra-plaque neovascularization as determined from histology specimens.

Imaging of the Carotid Artery Vulnerable Plaque

“…Contrast-Enhanced Ultrasound CEUS represents a simple and noninvasive technique for the evaluation of plaque vascularization, allowing for the detection of plaque vasa vasorum that are abundant in vulnerable plaques [86][87][88].…”

Improved plaque neovascularization following 2-year atorvastatin therapy based on contrast-enhanced ultrasonography: A pilot study

“…Such plaques are prone to rupture due to increased lipid content, macrophage density and intraplaque hemorrhage. Homogeneous echo plaques are also associated with an increased risk of ischemic stroke (12,35). Standard ultrasonography of the patients in the current study at baseline revealed either uniform or predominant echolucent lesions.…”

“…This has led to increasing interest in the inflammatory and histological processes that occur in atherosclerotic lesions and give rise to cerebrovascular events (34,35). A noninvasive method capable of evaluating plaque neovascularization is required to evaluate these processes.…”

Current Strategies and Possible Perspectives of Ultrasonic Risk Stratification of Ischemic Stroke in Internal Carotid Artery Disease

“…Currently, all the studies which use contrast-enhanced ultrasound for the detection and quantification of vasa vasorum employ visualbased semi-quantitative approaches [44 -46]. Shah et al used a semi-quantitative grading scale (grade 0 = no neovascularization, grade 1 = limited neovascularization, grade 2 = moderate neovascularization, grade 3 = pulsating, arterial vessel) to provide a distinction between the variations observed in intraplaque neovascularization [44]. Using a similar, dichotomous grading system, various recent studies categorized contrast-enhanced ultrasound enhancement as no contrast effect (grade 1) or high (grade 2) based on the visual detection of the contrast effect within the plaque [46].…”

“…Using a similar, dichotomous grading system, various recent studies categorized contrast-enhanced ultrasound enhancement as no contrast effect (grade 1) or high (grade 2) based on the visual detection of the contrast effect within the plaque [46]. Systematic histopathological validation revealed a direct positive correlation between contrast enhancement using this semi-quantitative grading scale and histology [44,45]. Furthermore, wholly consistent with the concept that more vulner- able plaque contains a higher degree of neovascularization, recent retrospective studies revealed the association between plaque enhancement on contrast-enhanced ultrasound imaging and clinical symptoms including cerebrovascular events in patients with carotid atherosclerosis [19,46,47].…”