Ultrasonic Assessment of Hepatic Blood Flow as a Marker of Mouse Hepatocarcinoma

Abstract Two-dimensional color-coded pulsed Doppler ultrasonography (US) with a 12-MHz linear transducer was used to follow tumor growth and neoangiogenesis development in 12 transgenic mice developing a whole liver hepatocellular carcinoma (HCC) induced by the expression of SV40-T antigen. In this model, male mice developed HCC at various temporal and histologic stages (hyperplastic, four–eight wk; nodular, 12 wk; diffuse carcinoma, 16–20 wk), whereas female mice remained tumor free. Seven age-matched tumor-free mice were used as controls. Liver volume was calculated from B-mode images of the abdomen. Blood flow waveforms were recorded from the hepatic tumor-feeding artery upstream from the tumor vessels, allowing quantitative blood flow velocity measurements. Measurements were performed every four weeks from four to 20 weeks. As early as the hyperplastic stage (eight weeks), liver volume was increased by 2.7-fold, hepatic artery peak-systolic blood flow velocities (BFV) by 1.5-fold, end-diastolic BFV by 1.6-fold and mean BFV by 2.0-fold compared with control values ( p < 0.001). Differences increased until 20 weeks and peak-systolic reached 90 ± 6, end-diastolic 54 ± 5 and mean BFV 48 ± 5 cm s–1 . Successive measurements of BFV were reproducible and intraobserver repeatability coefficient values were