Development of a Vascularized Carotid Artery Plaque Phantom for the Investigation of Novel Ultrasound-Based Technologies

Abstract

As the global burden of atherosclerotic cardiovascular disease continues to rise, there is an increased demand for improved imaging techniques for earlier detection and diagnosis of atherosclerotic plaques, and for quantitative measures of disease progression. Vulnerable plaque lesions are thought to be responsible for the majority of cardiovascular events, characterized by a large lipid core, a thin fibrous cap, and neovascularization – features that increase the risk of plaque rupture and thrombosis. Intraplaque neovascularization (IPN) in advanced lesions in the carotid artery can be visualized using contrast-enhanced ultrasound (CEUS) technology, and its accurate quantification could provide a powerful tool for the detection of vulnerable plaque. This project was undertaken to develop a model of vascularized atherosclerotic plaque compatible with CEUS, and to apply it in the validation of a novel IPN quantification tool that calculates a normalized IPN enhancement ratio (NER). A variety of plaque mimics (n=92) were created to simulate different plaque phenotypes, and NER values were compared with visual grading of human plaques (n=42). To validate the vulnerable plaque mimics, contrast enhancement of plaque IPN was evaluated using 2D and 3D methods, showing a positive correlation between NER and IPN volume (rho = 0.45; p<0.0001). Enhancement of certain plaque mimic types was shown to resemble human plaques with visual grade scores of 0 (NER score mean difference = 1.05 ± 2.45; p=0.67), grade 1 (NER score mean difference = 0.22 ± 3.26; p=0.95), and grade 2 (NER score mean difference = -0.84 ± 3.33; p=0.80). The NER quantification method was shown to detect grade 2 plaques with a sensitivity of 95% and specificity of 91%. This methodology was shown to successfully mimic plaque vulnerability and has the potential to improve clinical identification of vulnerable plaques. The neovascularized plaque phantom developed may serve as an in vitro platform for further validation of novel plaque imaging technologies and techniques for the investigation of plaque neovascularization.