Contrast-enhanced US quantitatively detects changes of tumor perfusion in a murine breast cancer model during adriamycin chemotherapy

Abstract

Currently used morphologic criteria have limitations in assessing tumor response to chemotherapy because of the relatively slow tumor shrinkage as measured by conventional morphologic imaging. Functional imaging techniques show promising results in early assessment of tumor response to treatment. To quantitatively detect changes in tumor perfusion during chemotherapy with contrast-enhanced ultrasound. Twenty-three MCF-7 breast cancer bearing nude mice treated by either adriamycin (n = 11) or sterile saline (n = 12) were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Regions of interest within the tumor were analyzed offline to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), and quality of fit (QOF). Hematoxylin and eosin was used to assess tumor cell density and immunohistochemical analysis was performed for evaluation of microvascular density (MVD). Treatment with adriamycin significantly reduced tumor growth in comparison to the control group (P < 0.001). There was no significant difference in perfusion parameters before treatment. Treatment with adriamycin resulted in a significant decrease in PE, WiAUC, WiR, and WiPI in comparison with control group (P < 0.01). The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors after treatment (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P < 0.001) after treatment. Quantitative contrast-enhanced ultrasound can detect the change of tumor perfusion after chemotherapy, which may enable early assess tumor response to chemotherapy.