Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma

To evaluate the diagnostic accuracy of perfluorobutane contrast-enhanced ultrasonography (CEUS) for hepatocellular carcinoma (HCC) and to explore how accuracy can be improved compared to conventional diagnostic criteria in at-risk patients.A total of 123 hepatic nodules (≥ 1 cm) from 123 at-risk patients who underwent perfluorobutane CEUS between 2013 and 2020 at three institutions were retrospectively analyzed. Ninety-three percent of subjects had pathological results, except benign lesions stable in follow-up images. We evaluated presence of arterial phase hyperenhancement (APHE), washout time and degree, and Kupffer phase (KP) defects. KP defects are defined as hypoenhancing lesions relative to the liver in KP. HCC was diagnosed in two ways: (1) Liver Imaging Reporting and Data System (LI-RADS) criteria defined as APHE and late (≥ 60 s)/mild washout, and (2) APHE and Kupffer (AK) criteria defined as APHE and KP defect. We explored grayscale features that cause misdiagnosis of HCC and reflected in the adjustment. Diagnostic performance was compared using McNemar's test.There were 77 HCCs, 15 non-HCC malignancies, and 31 benign lesions. An ill-defined margin without hypoechoic halo on grayscale applied as a finding that did not suggest HCC. Regarding diagnosis of HCC, sensitivity of AK criteria (83.1%; 95% confidence interval [CI]: 72.9-90.7%) was higher than that of LI-RADS criteria (75.3%; 95% CI: 64.2-84.4%; p = 0.041). Specificity was 91.3% (95% CI: 79.2-97.6%) in both groups.On perfluorobutane CEUS, diagnostic criteria for HCC using KP defect with adjustment by grayscale findings had higher diagnostic performance than conventional criteria without losing specificity.• Applying Kupffer phase defect instead of late/mild washout and adjusting with grayscale findings can improve the diagnostic performance of perfluorobutane-enhanced US for HCC. • Adjustment with ill-defined margins without a hypoechoic halo for features unlikely to be HCC decreases false positives for HCC diagnosis using the perfluorobutane-enhanced US. • After adjustment with grayscale findings, the sensitivity and accuracy of the APHE and Kupffer criteria were higher than those of the LI-RADS criteria; specificity was 91.3% for both.