Vascularized Carotid Atherosclerotic Plaque Models for the Validation of Novel Methods of Quantifying Intraplaque Neovascularization

Background: Intraplaque neovascularization (IPN) in advanced lesions of the carotid artery has been linked to plaque progression and risk of rupture. Quantitative measurement of IPN may provide a more powerful tool for the detection of such "vulnerable" plaque than the current visual scoring method. The aim of this study was to develop a phantom platform of a neovascularized atherosclerotic plaque within a carotid artery to assess new methods of quantifying IPN.

Methods: Ninety-two synthetic plaque models with various IPN architectures representing different ranges of IPN scoring were created and assessed using contrast-enhanced ultrasound. Intraplaque neovascularization volume was calculated from contrast infiltration in B mode. The plaque models were used to develop a testing platform for IPN quantification. A neovascularized enhancement ratio (NER) was calculated using commercially available software. The plaque model NERs were then compared to human plaque NERs (n = 42) to assess score relationship. Parametric mapping of dynamic intensity over time was used to differentiate IPN from calcified plaque regions.

Results: A positive correlation between NER and IPN volume (rho = 0.45; P < .0001) was found in the plaque models. Enhancement of certain plaque model types showed that they resembled human plaques, with visual grade scores of 0 (NER mean difference = 1.05 ± SE 2.45; P = .67), 1 (NER mean difference = 0.22 ± SE 3.26; P = .95), and 2 (NER mean difference = -0.84 ± SE 3.33; P = .80). An optimal cutoff for NER (0.355) identified grade 2 human plaques with a sensitivity of 95% and specificity of 91%.

Conclusions: We developed a carotid artery model of neovascularized plaque and established a quantitative method for IPN using commercially available technology. We also developed an analysis method to quantify IPN in calcified plaques. This novel tool has the potential to improve clinical identification of vulnerable plaques, providing objective measures of IPN for cardiovascular risk assessment.