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Review
. 2020 Aug;10(4):965-981.
doi: 10.21037/cdt.2020.01.08.

Contrast imaging ultrasound for the detection and characterization of carotid vulnerable plaque

Affiliations
Review

Contrast imaging ultrasound for the detection and characterization of carotid vulnerable plaque

Vasileios Rafailidis et al. Cardiovasc Diagn Ther. 2020 Aug.

Abstract

Not only the degree of luminal narrowing but also the plaque morphology and composition play an important role in risk stratification of carotid atherosclerotic lesions. During the last few years, carotid contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging tool to assess such vulnerable carotid plaques. This review article discussed the use of CEUS for the detection of carotid plaque irregularities and ulcerations as well as the quantification of intraplaque neovascularization and its correlation with histology and inflammatory biomarkers. Apart from evaluating for markers of vulnerable carotid plaques, CEUS enhancement is directly associated with past cerebrovascular events. More importantly, preliminary evidence has shown that CEUS could be used to predict future cerebrovascular and cardiovascular events. Despite the progress in CEUS imaging for carotid atherosclerotic disease, past studies still suffer from the retrospective nature, small sample size, and a lack of matched, well controlled prospective studies. In the future, large multi-center prospective studies addressing the relationship between CEUS findings and patient clinical outcomes in carotid atherosclerotic disease are warranted.

Keywords: Carotid plaque; contrast-enhanced ultrasound (CEUS); neovascularization; ulceration; ultrasound.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt.2020.01.08). The series “Advanced Imaging in The Diagnosis of Cardiovascular Diseases” was commissioned by the editorial office without any funding or sponsorship. SP and DS serve as the unpaid editorial board members of Cardiovascular Diagnosis and Therapy from July 2019 to June 2021. DS reports grants from Bracco SA, outside the submitted work. PSS reports personal fees from Bracco SA, outside the submitted work. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
An asymptomatic 63-year-old patient with ulcerated severely stenotic internal carotid artery plaque. Colour Doppler image (A) shows the presence of echogenic plaque in the origin of internal carotid artery. Due to overwriting artifact, the plaque’s border cannot be accurately detected, while the plaque appears irregular. On CEUS (B), an ulceration is detected (arrowhead), and the severely stenotic lumen can be followed. Note the presence of calcification projected in this contrast-specific image (arrow), which should not be mistaken for intraplaque neovessels or ulceration. MDCTA (C) confirming CEUS findings and the presence of ulceration (arrowhead). CEUS, contrast-enhanced ultrasound; MDCTA, multi-detector computed tomography angiography.
Figure 2
Figure 2
A male patient with a mixed echogenicity atherosclerotic plaque of the internal carotid artery. An example of a surface irregularity quantification software using colour Doppler image (A). Note the delineation of plaque surface with a red line and the outer vascular wall with a blue line. Parts of the lumen are not filled with blood flow signals (asterisk), while parts of the plaque surface may be obscured by overwriting artifact. Same software using a CEUS image (B), where the lumen is fully filled with microbubbles and the plaque surface can be better appreciated and delineated. CEUS, contrast-enhanced ultrasound.
Figure 3
Figure 3
A 58-year-old male patient with acute stroke and free-floating thrombus in an internal carotid artery plaque. Colour Doppler technique (A) fails to fully visualize blood flow, raising suspicion of a filling defect within the lumen. CEUS (B) accurately demonstrates an intraluminal filling defect (asterisk), circumferentially delineated by microbubbles (arrowheads). A “donut-like” appearance is thus created suggesting intraluminal thrombus. MDCTA (C) confirms CEUS findings, providing a similar appearance. CEUS, contrast-enhanced ultrasound.
Figure 4
Figure 4
Semi-quantitative, visual-based analysis of intraplaque neovascularization using a 3-point grading system. Plaques at the origin of the internal carotid artery on B-mode ultrasound (right side) and CEUS imaging (left side) in three different patients. Grade 1 (A): carotid plaque with no intraplaque neovascularization defined as no appearance of moving microbubbles in the plaque or confined only to the adjacent adventitial layer. Grade 2 (B): carotid plaque with limited or moderate intraplaque neovascularization defined as moderate visible appearance of moving bubbles in the plaque at the adventitial side or plaque shoulder (arrows). Grade 3 (C): carotid plaque with extensive intraplaque neovascularization defined as clear visible appearance of bubbles moving to the plaque core (arrows).
Figure 5
Figure 5
Quantitative analysis of intraplaque neovascularization using the VueBox® (Bracco SA) plaque package software. After bolus injection of Sonovue® the enhancement within a region of interest of the plaque (green line) compared to the lumen (yellow line) on a time intensity curve is used for quantitative analysis of intraplaque neovascularization. Intraplaque perfusion is visualized by a parametric color imaging (right side). Furthermore, different perfusion parameters including the relative perfused area (rPA) of the plaque can be analysed. In the presented analysis calculated a rPA of 45% within the plaque corresponding to moderate (grade 2) intraplaque neovascularization.

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