Identification of neovascularization by contrast–enhanced ultrasound to detect unstable carotid stenosis

Abstract

BackgroundPlaque neovascularization accompanies local inflammation and critically contributes to plaque instability. Correct identification of intraplaque neovascularization by contrast–enhanced ultrasound (CEUS) may provide an additional risk marker in carotid stenosis. This pilot study investigates the correlation between histological evaluation of carotid plaque specimens and pre-surgery CEUS to identify neovascularization.Methods17 patients with high-grade internal carotid artery (ICA) stenosis were studied. CEUS was performed in all patients shortly before carotid endarterectomy. Neovascularization, infiltration of T cells and macrophages along with intraplaque hemorrhage were studied in excised plaques by immunohistochemistry. Ultrasound-based four-level and two-level classification systems for neovascularization were used. CEUS findings were compared with histological findings.ResultsScores on the CEUS-based four-level and two-level classifications were robustly correlated with the density of intraplaque vessels (r = 0.635, p = 0.006 and r = 0.578, p = 0.015, respectively). Histological evaluation of regions with strong and prolonged intraplaque enhancement typically showed strong intraplaque neovascularization in conjunction with acute intraplaque hemorrhage. Moreover, higher grades of intraplaque neovascularization as determined by ultrasound were associated with a higher percentage of macrophage-rich areas.ConclusionCEUS is a technique well suited to gauge the degree of neovascularization of carotid plaques. Future research will have to define the reliability and validity of CEUS in everyday clinical practice. Further, our study suggests that CEUS may also be useful to pick up features of vulnerable plaques such as acute intraplaque hemorrhages.

Relation between carotid vulnerable plaques and peripheral leukocyte: A case-control study of comparison utilizing multi-parametric CEUS

“…A clinical study demonstrated that with intraplaque hypermetabolism, high-oxygen consumption macrophages more easily produce a hypoxic microenvironment compared with increased intima-media thickness [32]. Oxygen diffusive disorder in thickened intima-media and increased oxygen consumption of inflammatory cells both lead to a hypoxic microenvironment state and stimulate neovascularization, intraplaque hemorrhage, and the rupture of atherosclerotic plaques [7]. A recent study showed that the adventitia not only provides structural support for the vessel walls but also facilitates atherosclerosis, as well as the formation of neo-intima and vulnerable plaques by "outside-in" inflammatory cells and the transfer of fibroblasts [33].…”

“…Contrast-enhanced ultrasound (CEUS) provides direct visualization of the IPN in carotid plaques [6]. A number of studies have recently described a positive correlation between the histological density of neovessels and the presence of neovascularization in carotid plaques detected by CEUS [7].…”

The Role of Neurosonology in the Diagnosis and Management of Patients with Carotid Artery Disease: A Review

“…In their study, intensity of enhancement corresponding to intraplaque vessel content, and wash‐in‐time reflecting the speed of flow within the plaque, were significantly associated with stroke risk . Importantly, intraplaque enhancement in contrast‐enhanced ultrasound studies correlates well with histologically verified intraplaque neovascularization and hemorrhage as well as macrophage infiltration …”

“…The method includes injection of a contrast agent consisting of microbubbles, and the subsequent identification of micorbubbles within the vessels of the plaque after they have entered the arterial system through the pulmonary circulation . Both visual grading and semiautomated techniques have been used to evaluate neoangiogenesis . Huang et al proposed a classification method to quantify the intensity of intraplaque enhancement as grade I for plaques with no enhancement, grade II with only arterial wall vasa vasorum enhancement, grade III with arterial wall vasa vasorum and plaque shoulder enhancement, and grade IV with extensive and internal plaque enhancement.…”

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology

“…The analysis concerning the degree of intraplaque neovessels reported that some quantitative parameters on CEUS could replace qualitative visual scoring [4]. A pilot study indicated the association of the quantitative assessment of neovascularization with intraplaque hemorrhage [5]. Furthermore, a meta-analysis reported that CEUS is a useful, noninvasive modality for the diagnosis of intraplaque neovascularization [6].…”