Contrast-enhanced ultrasound imaging of tumor xenografts with comparison to intratumoral pressure after vascular-disrupting treatment

Contrast-enhanced ultrasound (CEUS) is a noninvasive imaging modality that allows the study of tissue blood flow at the microvascular level. The objective of this study was to investigate the tumor perfusion using CEUS imaging and relationship to direct measurements of intratumoral pressure after administration of a vascular-disrupting treatment. Four female mice were implanted with breast cancer cells in the mammary fat pad and tumors were allowed to grow for about four weeks. Before and after microbubble (MB) dosing via a tail vein catheter, nonlinear CEUS imaging was performed along the largest tumor cross-section. Following baseline CEUS imaging, 20 mg/kg of combretastatin A-4 phosphate (CA4P) was administered using the placed catheter. After treatment, CEUS imaging was performed again at 4 or 24 h. Direct local pressure measurements were taken within the ultrasound (US) imaging plane with a calibrated pressure catheter. After euthanasia, tumors were removed for ex vivo analysis. CEUS images were analyzed offline using the Vevo Lab Software. Small region-of-interests (ROIs) were selected to match the locations where the pressure catheter tip was positioned for comparison. Considerable changes in CEUS images were found after tumor treatment. Intratumoral pressure measurements were significantly lower at 24 h compared to those obtained at 4 h (p = 0.01).