Regions of interest and parameters for the quantitative analysis of contrast-enhanced ultrasound to evaluate the anti-angiogenic effects of bevacizumab

Abstract

The aim of the present study was to identify effective regions of interest (ROIs) and parameters for the quantitative analysis of contrast-enhanced ultrasound (CEUS) to evaluate the anti-angiogenic effects of bevacizumab. Thirty mice were subcutaneously injected with CT26 cells and randomly divided into a bevacizumab-treated (Bev) group and a control group (normal saline-treated). CEUS and quantitative analysis were performed on days 7, 11, 14 and 21 following tumor establishment. ROItotal, which included the whole tumor, and ROIsmall, which included the most enhanced part of the tumor, were selected and outlined. Parameters including time to peak (TTP), maximum intensity (Imax) and area under the curve (AUC; in addition to rates of AUC 1, AUC2, AUCfast and AUCslow) were recorded. The tumors were resected on day 21 for microvessel density (MVD) counting. Our results showed that the MVD in the Bev group was significantly lower compared with that in the control group (4.09 vs. 6.41; P=0.001). Additional parameters of ROIsmall were identified to be significantly different between the two groups, compared with those of ROItotal. No significant differences in TTP and Imax were observed between the two groups at the four time-points examined (P>0.05). For the AUC parameters in ROI small, AUC and the rates of AUC2, AUCfast and AUCslow were lower in the Bev group compared with those in the control group on days 7 and 11 (P<0.05). These findings indicate that ROIsmall and AUC parameters in the quantitative analysis of CEUS may be useful for the evaluation of changes in tumor angiogenesis following bevacizumab treatment.