Spatio-temporal Quantification of Carotid Plaque Neovascularization on Contrast Enhanced Ultrasound: Correlation with Visual Grading and Histopathology

Abstract

To evaluate whether carotid intraplaque neovascularization (IPN) can be accurately assessed by two types of quantitative analysis on contrast enhanced ultrasound (CEUS), the time intensity curve analysis and the analysis of contrast agent spatial distributions, and whether the quantitative analysis correlates with semiquantitative visual interpretation and histopathology. Forty-four plaques in 34 patients were included for CEUS examination. A three point score system (absent, moderate, and extensive) was used for semiquantitative grading of IPN. Eight spatial quantitative parameters were derived, including the IPN area ratio in plaque (AR) and the AR in plaque core (AR13). Two temporal quantitative parameters were obtained, namely the enhanced intensity in plaque (EI) and the enhanced intensity ratio (EIR). Histopathology with CD34 staining for quantification of microvessel density (MVD) was performed on 12 plaques excised by carotid endarterectomy. Both spatial and temporal parameters were correlated with MVD on histology (AR: r = .854; AR13: r = .858; EI: r = .767; EIR: r = .750 [p < .01]), as well as with semiquantitative grading (p < .01). Five mutually independent factors were condensed from 10 interrelated parameters by using factor analysis, and they significantly predicted MVD with an radj value as high as .932 (p = .01). Both spatial and temporal analysis on CEUS can accurately assess IPN. Combining them provides better IPN assessment and may be useful for plaque vulnerability evaluation and risk stratification.