Efficacy of Perflubutane Microbubble-Enhanced Ultrasound in the Characterization and Detection of Focal Liver Lesions: Phase 3 Multicenter Clinical Trial

The purpose of this study was to assess the efficacy and safety of contrast-enhanced ultrasound performed with perflubutane microbubbles in comparison with unenhanced ultrasound and dynamic CT in the characterization of focal liver lesions during the vascular phase of imaging and in the detection of lesions during the Kupffer phase.A total of 196 patients were enrolled at 15 centers in Japan. Vascular phase images were obtained before contrast injection until 1 minute after injection. Kupffer phase images were obtained 10 minutes after injection. Dual-phase CT was performed as determined by standard clinical practice at each center. Unenhanced ultrasound, contrast-enhanced ultrasound, and CT images were read by blinded reviewers, and the results they reached regarding characterization and detection were compared with reference standard findings made by onsite investigators. The safety observation period was 72 hours after contrast administration.Among the 190 patients included in the characterization analysis, the accuracy of contrast-enhanced ultrasound (88.9%) was significantly greater than that of unenhanced ultrasound (68.4%) and dynamic CT (80.5%) (p < 0.001 and p = 0.008). Among the 191 patients in the detection analysis, the efficacy of contrast-enhanced ultrasound in detection of lesions was significantly higher than that of unenhanced ultrasound and dynamic CT (p < 0.001 and p = 0.008), predominantly because more metastatic lesions were detected (both p < 0.001). In particular, contrast-enhanced ultrasound was superior to dynamic CT in the detection of metastatic lesions measuring 1 cm or smaller. The incidence of adverse events was 49.2% and that of adverse drug reactions was 10.4%. All adverse drug reactions were mild.Compared with unenhanced ultrasound and dynamic CT, contrast-enhanced ultrasound with perflubutane microbubbles improved diagnostic efficacy in both characterization and detection of focal liver lesions with no serious adverse drug reactions.