Early Changes in Contrast Enhanced Ultrasound Predict for Pathologic Response to Chemotherapy in an Animal Tumor Model

Abstract

The purpose of this study was to examine CEUS whether could earlier predict pathologic response to chemotherapy than morphologic method in a MCF-7 tumor model. Twenty MCF-7 breast cancer bearing nude mice were included in this study. Animals received either adriamycin or a control substance were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Dynamic contrast enhanced ultrasound was performed at pretherapy, Day 3, Day 5 and Day 7 after adriamycin administration. Regions of interest within the tumor were analyzed off-line to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WIAUC), wash-in rate (WIR), wash-in perfusion index (WIPI) and quality of fit (QOF). The section equivalent to ultrasound imaging plane was stained with Hematoxylin and Eosin to allow for assessment of tumor cell density and Ki67 for situation of tumor proliferation, CD34 for tumor micro-vascular density. There were no significant differences in tumors perfusion and tumor volumes before treatment. Treatment with adriamycin resulted into a significant decrease in PE, WIAUC, WIR and WIPI in comparison with control group (P < 0.05) at Day 3, when there was no significant difference in tumor volume. The volume of treated tumors was significant smaller than that of control tumors (P < 0.05) at day 7. The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The positive Ki67 cell density and CD34 estimated by pathology slice were also significantly lower in treated tumors than in control tumors at day 7 (P < 0.05). The correlation between micro-vascular and perfusion parameters was obvious (P < 0.05). Changes in tumor micro-vessel functionality as depicted by CEUS early on after starting adriamycin -based chemotherapy can predict final pathologic response. Contrast enhanced ultrasound will be a new way for evaluating tumor response to chemoth.