Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane for the Diagnosis of Hepatocellular Carcinoma in Individuals with High Risk

Background Perfluorobutane (PFB) and sulfur hexafluoride (SHF) have different physiologic characteristics, but it is unclear whether hepatocellular carcinomas (HCCs) show similar wash-in and washout patterns to both contrast agents at US. Purpose To investigate Contrast-Enhanced US Liver Imaging Reporting and Data System (LI-RADS) version 2017 HCC categorization by comparing PFB-enhanced US and SHF-enhanced US in participants at high risk for HCC. Materials and Methods In this prospective study conducted from February to August 2019, participants at high risk for HCC with treatment-naive hepatic observations (≥1 cm) categorized as LR-3, LR-4, LR-5, or LR-M (intermediate probability of HCC, probable HCC, definitely HCC, and probably malignant but not HCC specific, respectively) on cross-sectional images were screened. They underwent same-day PFB-enhanced US and SHF-enhanced US. Arterial phase hyperenhancement (APHE), washout time and degree, and echogenicity in the Kupffer phase (PFB-enhanced US) were evaluated and categorized by the operator using CEUS LI-RADS, who referred to the radiologist who performed the contrast-enhanced US, and by a reviewer. Diagnostic performance was analyzed using the McNemar test. Results Fifty-nine participants were evaluated (43 with HCC, 10 with non-HCC malignancies, six with benign findings). Nonrim APHE was identically observed in 95% (41 of 43, operator) or 88% (38 of 43, reviewer) of HCCs with both contrast agents. Among 43 HCCs, late (≥60 seconds) and mild washout were more frequent with PFB-enhanced US (34 with operator, 33 with reviewer) than with SHF-enhanced US (24 with operator, 26 with reviewer) (P = .04 or P = .12). The washout time for HCCs was later at PFB-enhanced US (median, 101 seconds ± 11) than at SHF-enhanced US (median, 84 seconds ± 5; P = .04). Sensitivity (34 of 43; 79%; 95% confidence interval [CI]: 64%, 90%) was higher with PFB-enhanced US than with SHF-enhanced US (23 of 43; 54%; 95% CI: 38%, 67%; P = .01). Specificity was 100% (95% CI: 79%, 100%) with both. Hypoenhancement in the Kupffer phase was more common in malignant (49 of 53 [92%] for both operator and reviewer) than in benign (two of six [33%] for operator, one of six [16%] for reviewer) lesions. Conclusion On the basis of the Contrast-Enhanced US Liver Imaging Reporting and Data System version 2017 algorithm, noninvasive US diagnosis of hepatocellular carcinoma by using perfluorobutane-enhanced US had higher diagnostic performance than sulfur hexafluoride-enhanced US, without loss of specificity. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kim and Jang in this issue.