Abstract
This study used an atherosclerotic rabbit model to investigate the feasibility of quantifying adventitial vasa vasorum (VV) via contrast-enhanced ultrasound (CEUS) imaging to identify early atherosclerosis. Recent evidence has linked adventitial VV with atherosclerotic plaque progression and vulnerability. A growth in VV density has been detected preceding intimal thickening and even endothelial dysfunction. In our study, carotid atherosclerosis rabbit models were used, and animals underwent CEUS imaging at the end of the atherosclerotic induction period. Normalized maximal video-intensity enhancement (MVE) was calculated to quantify VV density. After CEUS imaging, animals were euthanized, and their carotids were processed for histopathological analysis following staining for CD31 and VEGF. Adventitial normalized MVE increased as atherosclerosis progressed (p < 0.001), and normalized MVE also progressed, demonstrating a linear correlation with histological findings (r = 0.634, p < 0.001 for VEGF-positive; r = 0.538, p < 0.001 for CD31-positive). Thus, we histologically validated that CEUS imaging can be used to quantify the development of adventitial VV associated with atherosclerosis progression. This method can be used for monitoring the VV to detect early atherosclerosis.
Highlights
Specimens do not include the entire arterial wall and because there is a possibility of high-risk lesions being missed during sample collection, histology cannot entirely confirm the imaging results despite the promising potential application of contrast-enhanced ultrasound (CEUS) imaging in the clinical setting
We explored the feasibility of CEUS imaging for visualizing the neovascularization in the adventitial vasa vasorum (VV) in rabbit models with different degrees of atherosclerosis caused by a high-fat diet with or without balloon injury
Our findings demonstrated that CEUS imaging could be used as a quantitative approach to demonstrate adventitial VV in early atherosclerosis before intimal changes
Summary
Specimens do not include the entire arterial wall and because there is a possibility of high-risk lesions being missed during sample collection, histology cannot entirely confirm the imaging results despite the promising potential application of CEUS imaging in the clinical setting. Further validation of CEUS imaging to quantitate VV density over the time course of plaque evolution is indispensable to its clinical application. The current study was designed to investigate the feasibility of quantitative CEUS imaging for the in vivo visualization of intraplaque and adventitial neovascularization during atherosclerosis progression. Serial CEUS imaging was performed in an experimental carotid atherosclerotic rabbit model, with systematic histological assessment as the reference standard
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