Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility

PURPOSE: To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility. MATERIALS AND METHODS: For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed. RESULTS: In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x10(3)±1.68 x10(3) vs 5.55x10(2)±4.65x10(2), p = 0.010) and wash-in and wash out AUC ((WiWo)AUC, 1.07x10(5)±6.48 x10(4) vs 2.65x10(4)±2.25x10(4), p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x10(3)±7.53x10(2) vs 9.43x10(2)± 7.81 x10(2), p = 0.632) and (WiWo)AUC (5.09 x10(4)±3.25x10(4) vs 5.92 x10(4)±3.20x10(4), p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01–0.63). However, inter-operator reproducibility of important perfusion parameters, including (Wi)AUC, (Wo)AUC, and (WiWo)AUC, ranged from fair to excellent (ICC: 0.59–0.93) in a different scanner. CONCLUSION: Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.