Detection of Adventitial Vasa Vasorum and Intraplaque Neovascularization in Carotid Atherosclerotic Lesions with Contrastenhanced Ultrasound and their Role in Atherosclerosis

Introduction

The development of new surrogate markers of atherosclerosis is a crucial goal in the clinical setting, as they may allow physicians to recognize unstable lesions early and identify individuals with vulnerable or unstable lesions who bear an increased risk of future cardio- and cerebrovascular complications.^{1, 2} These surrogate markers should be capable of being measured noninvasively using safe and reliable methods.³ Recently, Nambi et al. demonstrated how the combined measurement of carotid intima media thickness (CIMT) and occurrence of carotid plaques improves the risk prediction of cardiovascular outcomes.⁴ These results confirm the value of carotid ultrasound (US) when combined with traditional Framingham risk factors in assessing a patient’s risk for atherosclerotic disease.

Contrast-enhanced ultrasound (CEUS) is a new imaging approach that is evolving and may become a standard clinical tool for further atherosclerotic risk stratification in the future.⁵ The contrast agents used in US imaging are safe, commercially available, and approved for use in echocardiography by the FDA.⁶ Thus, CEUS is technically feasible with existing approved commercial equipment and can be performed at the bedside or in an outpatient setting. However, US contrast agents are not yet approved by the FDA for visualization and assessment of the carotid artery and its associated pathologies. The cost effectiveness of CEUS has been shown in the context of gastrointestinal imaging,⁷ and CEUS of carotid atherosclerotic lesions is emerging as an approach to complement unenhanced US imaging.⁸ By providing the direct visualization of adventitial vasa vasorum (VV) and intraplaque neovascularization, CEUS is capable of depicting two new surrogate markers of atherosclerosis — namely, adventitial VV and intraplaque neovascularization.^{5, 9}