Neovascularization From the Carotid Artery Lumen Into the Carotid Plaque Confirmed by Contrast-Enhanced Ultrasound and Histology.

Objective: This study was aimed at assessing intraplaque neovessels, focusing on neovascularization from the vascular luminal side using contrast-enhanced ultrasound (CEUS) and determining that this contrast effect indicates that the neovessel is connected to the vessel lumen histopathologically. Whether plaque vulnerability can be assessed more accurately was also investigated.
Methods: We enrolled consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and pre-operative CEUS with perflubutane of the carotid arteries. We graded the contrast effect semi-quantitatively from the vascular luminal and adventitial sides. We compared the contrast effect with the pathological findings, especially the neovascularization of the CEA specimens.
Results: In total, 68 carotid arterial atheromatous plaques (47 symptomatic) were analyzed. Symptomatic plaques were significantly correlated with stronger contrast effects from the luminal side than from the adventitial side (p = 0.0095). Microbubbles from the luminal side appeared to flow mainly into the plaque shoulder. The contrast effect value for the plaque shoulder and neovessel density were significantly correlated (ρ = 0.35, p = 0.031). Neovessel density was significantly higher in symptomatic than in asymptomatic plaques (56.2 ± 43.7/mm ² and 18.1 ± 15.2/mm ² , respectively, p < 0.0001). Serial histological sections of CEA specimens in a symptomatic plaque with a strong contrast effect from the luminal side revealed multiple neovessels fenestrated to the vessel lumen with endothelial cells, consistent with the CEUS findings.
Conclusion: Contrast-enhanced ultrasound can be used to evaluate neovessels originating from the luminal side, histopathologically confirmed in serial sections. Symptomatic vulnerable plaque is correlated more significantly with intraplaque neovascularization from the luminal side than with neovascularization from the adventitia.
Competing Interests: Conflict of interest K. Saito reports lecturer's fees from GE Healthcare LLC, Takeda, Sumitomo Pharma, Daiichi Sankyo, Otsuka Pharmaceutical and Bayer outside the submitted work. H.K. reports research funding and lecturer's fees from Eizai, Daiichi Sankyo, Otsuka Pharmaceutical, CSL Behling, Abbott, Astellas, Bayer, JB, Kaneka, and Carl Zeiss outside the submitted work. K.I. reports grant support from Chugai Pharmaceutical Company Limited, Eisai Company, KM Biologics Company Limited, Nihon Medi-Physics, Nippon Zoki Pharmaceutical, Otsuka Pharmaceutical Company Limited and Idorsia Pharmaceuticals Japan Limited outside the submitted work. M.K. reports honoraria from Daiichi-Sankyo and research support from Daiichi-Sankyo, Nippon Boehringer Ingelheim and Shionogi, all of which are outside of the submitted work. K.T. reports lecturer's fees from Daiichi Sankyo, Otsuka, Novartis, Bayer, Bristol-Myers Squibb and Abbott Medical outside the submitted work. M.I. reports lecturer's fees from Daiichi Sankyo and Eisai and grant support from Panasonic, GE Healthcare LLC, Bristol-Myers Squibb and Shimadzu Corporation, all of which are outside of the submitted work. The other authors declare no competing interests.
(Copyright © 2023. Published by Elsevier Inc.)