Quantification of carotid plaque elasticity and intraplaque neovascularization using contrast-enhanced ultrasound and image registration-based elastography

Abstract

It is valuable for evaluation of carotid plaque vulnerability to investigate the relation between intraplaque neovascularization (IPN) and plaque elasticity. The contrast-enhanced ultrasound (CEUS) has been used in IPN measurement, but it cannot assess plaque elasticity. The aim of this study was to develop an ultrasound elastography technique based on registration of CEUS sequential images and to use this technique for direct comparison between IPN and plaque elasticity. We employed a nonrigid image registration method using the free-form deformation model to register a pair of clinical CEUS images at systole and diastole. The 2D displacement field of the plaque was estimated and then utilized to calculate the axial and lateral strain distributions within the plaque, from which quantitative strain parameters were obtained. The IPN was measured semiquantitatively with visual assessment and quantitatively with the time–intensity curve analysis and the analysis of contrast agent spatial distributions. Histopathology with CD34 staining for quantification of microvessel density (MVD) was performed on plaques excised by carotid endarterectomy. Simulation experiments showed that the mean absolute error and the root mean squared error of the displacement estimation were 0.325±0.180 pixel (7.2%±3.8%) and 0.556±0.284 pixel (12.3%±6.1%), respectively, demonstrating high accuracy of the elastography technique. Thirty-eight plaques in 29 patients met the inclusion criteria for the elastography and image analysis, where ten plaques underwent endarterectomy. The 95th percentile (A95) and standard deviation (Asd) of the axial strains exhibited significant differences between the low and high grades of IPN visually assessed (p<0.01). A95 (R=0.579; p<0.001) and Asd (R=0.609; p<0.001) were correlated with the enhanced intensity of plaque, and also correlated with the MVD (R=0.793 and 0.817, respectively; p<0.01), suggesting that plaque became softer and more elastically heterogeneous as IPN increased. These findings provide direct and quantitative evidence for the associations between plaque strains and IPN and might be helpful for evaluation of carotid plaque vulnerability and for plaque risk stratification.