Detection of Carotid Atherosclerotic Plaque Neovascularization Using Contrast Enhanced Ultrasound: A Systematic Review and Meta-Analysis of Diagnostic Accuracy Studies

Background Intraplaque neovascularization is considered an important indicator of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) of carotid arteries improves imaging of carotid intima-media thickness and permits real-time visualization of neovascularization of the atherosclerotic plaque. The authors conducted a systematic review and meta-analysis to evaluate the accuracy of CEUS-detected carotid atherosclerotic plaque. Methods A systematic search was performed to identify studies published in the MEDLINE, Embase, Scopus, and Web of Science databases from 2004 to June 2015. Studies evaluating the accuracy of quantitative analysis and qualitative analysis (visual interpretation) for the diagnosis of intraplaque neovascularization compared with histologic specimens and/or clinical diagnosis of symptomatic plaque were included. Parameters evaluated were plaque quantitative CEUS intensity and the visual grading of plaque CEUS. A random-effects meta-analysis was used to pool the likelihood ratios (LRs), diagnostic odds ratios, and summary receiver operating characteristic curves. Corresponding areas under the curves were calculated. Results The literature search identified 203 studies, 20 of which were selected for systematic review; the final meta-analysis included seven studies. For qualitative CEUS, pooled sensitivity was 0.80 (95% CI, 0.72-0.87), pooled specificity was 0.83 (95% CI, 0.76-0.89), the pooled positive LR was 3.22 (95% CI, 1.67-6.18), the pooled negative LR was 0.24 (95% CI, 0.09-0.64), the pooled diagnostic odds ratio was 15.57 (95% CI, 4.94-49.03), and area under the curve was 0.894. For quantitative CEUS, pooled sensitivity was 0.77 (95% CI, 0.71-0.83), pooled specificity was 0.68 (95% CI, 0.62-0.73), the pooled positive LR was 2.34 (95% CI, 1.69-3.23), the pooled negative LR was 0.34 (95% CI, 0.25-0.47), the pooled diagnostic odds ratio was 7.06 (95% CI, 3.6-13.82), and area under the curve was 0.888. Conclusions CEUS is a promising noninvasive diagnostic modality for detecting intraplaque neovascularization. Standardization of quantitative analysis and visual grading classification is needed to increase reliability and reduce technical heterogeneity.