Contrast-Enhanced Gray-Scale Ultrasound for Quantitative Evaluation of Tumor Response to Chemotherapy: Preliminary Results With a Mouse Hepatoma Model

The purpose of this study was to quantify tumor blood perfusion with contrast-enhanced gray-scale ultrasound in the evaluation of tumor response to chemotherapy.Mice bearing H22 hepatoma were treated with cisplatin or placebo by intraperitoneal injection. Contrast-enhanced gray-scale ultrasound was performed on day 8 after bolus injection of a lipid-based ultrasound contrast agent. Regions of interest within the tumor were analyzed offline to determine area under the curve, maximum intensity, perfusion index, mean transit time, time to peak, and quality of fit. Immediately after imaging, mice were euthanized, and tumor tissue was removed for fixation in 10% formalin solution. Microvascular density was measured after anti-CD34 staining.The volume of treated tumors was significantly smaller than that of control tumors (p0.001). Treatment with cisplatin resulted in a significant decrease in perfusion index and maximum intensity compared with control tumors (p0.05). There were no significant differences between control and treated tumors (p0.05) with respect to area under the curve, mean transit time, and time to peak. The microvascular density of treated tumors was significantly lower than that of control tumors (p0.001).Quantitative analysis of tumor blood perfusion with contrast-enhanced ultrasound can be used for noninvasive assessment of functional changes in tumors after chemotherapy.