In Vivo Assessment of Atherosclerotic Plaque Neovascularization by Contrast-Enhanced Ultrasound: An Unsolved Mystery?

Computational imaging of aortic vasa vasorum and neovascularization in rabbits using contrast enhanced intravascular ultrasound: association with histology analysis

“…However, because of ethical and methodological issues, only few, small-sized studies incorporate both ultrasonographic and histological data assessment. Moreover, a series of other limitations have been a point of dispute ( 30 ). The automated quantification of VV by computational methods is very limited and the validity of the few existing tools is unexplored.…”

Authors' Reply

“…Our meta-analysis further supports the role of contrast-enhanced ultrasound (CEUS )in correctly identifying IPN, which is a surrogate for the underlying inflammatory process that could potentially aid in the risk stratification of patients with carotid stenosis. Vrachatis et al 1 accurately point out that our report also outlined the challenges of CEUS in evaluating the dynamicity of IPN, some of which include the multiple heterogeneous factors that affect the visualization of microbubbles within carotid plaques, homeostatic variability of vascular regulation, plaque topography, the technical limitations of delivering a uniform ultrasonic field, and the need for development and standardization of technology to optimize acquisition and interpretive analysis of IPN. 3 More specifically, it might be challenging for CEUS to differentiate between contrast microbubbles located in the neovessels (as in IPN) and those freely moving within the plaque after acute neovessel rupture (intraplaque hemorrhage).…”

“…In a recent issue of JASE, Huang et al 1 presented an interesting metaanalysis regarding the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) for the detection of carotid atherosclerotic intraplaque neovascularization (IPN). Beyond the meta-analysis, which was limited to studies that provided data regarding the sensitivity and specificity of CEUS in the recognition of IPN, the investigators also conducted an extensive review of the available literature, for which they should be congratulated.…”

“…[2][3][4] Several methods have been proposed for in vivo imaging and quantification of IPN, 3,5,6 but CEUS remains the most widely applied and examined technique. However, as Huang et al 1 noted, studies using CEUS suffer from both a lack of standardization regarding protocols used for CEUS-assisted identification of IPN and substantial variance in reporting of their findings. Moreover, regarding IPN quantification protocols, a number of limitations are comprehensively summarized by Huang et al Still, we would like to underline a couple of further issues.…”

“…In particular, when plaques located in the posterior arterial wall are evaluated, microbubbles may produce acoustic shadowing that alters grayscale intensity and therefore image interpretation, a phenomenon known as far-wall pseudoenhancement. 8 Finally, an issue pinpointed as a limitation by Huang et al 1 is the identification of the truly culprit plaques in the case of cerebrovascular events. The investigators assumed that in symptomatic patients, the evaluated plaque (under CEUS) should be the culprit one, but this may not be always the case.…”