Contrast-Enhanced Ultrasound Using Perfluorobutane: Impact of Proposed Modified LI-RADS Criteria on Hepatocellular Carcinoma Detection

BACKGROUND. Contrast-enhanced ultrasound (CEUS) LI-RADS version 2017 (v2017) applies only to CEUS examinations performed using pure blood pool agents, noting that future versions will address combined blood pool and Kupffer cell agents such as perfluorobutane. Such agents may improve hepatocellular carcinoma (HCC) detection by visualization of a defect in the Kupffer phase (obtained >= 10 minutes after injection). OBJECTIVE. The purpose of our study was to compare the diagnostic performance of the LR-5 category for HCC detection in at-risk patients between CEUS LI-RADS v2017 and proposed modified criteria for CEUS examinations performed using perfluorobutane. METHODS. This retrospective study included 293 patients at risk for HCC (259 men, 34 women; mean age, 55 +/- 12 [SD] years) who underwent CEUS using perfluorobutane from March 1, 2020, to October 30, 2020, showing a total of 304 observations (274 HCC, 14 non-HCC malignancy, and 16 benign lesions). Two readers independently assessed examinations and assigned categories using both CEUS LI-RADS v2017 and the proposed modified criteria. In the modified criteria, observations 10 mm or greater with not rim arterial phase hyperenhancement (APHE), no washout, and a Kupffer defect were upgraded from LR-4 to LR-5, and observations 10 mm or greater with not rim APHE, early washout, and a mild Kupffer defect were reassigned from LR-M to LR-5. Interreader agreement was assessed, and consensus interpretations were reached. Diagnostic performance was evaluated. RESULTS. Interreader agreement for LI-RADS category assignments, expressed using kappa coefficients, was 0.839 for CEUS LI-RADS v2017 and 0.854 for the modified criteria. Modified criteria upgraded 35 observations from LR-4 to LR-5 on the basis of a Kupffer defect, of which 34 were HCC and one was benign. Modified criteria reassigned 22 observations from LR-M to LR-5 on the basis of a mild Kupffer defect, of which all were HCC. LR-5 using modified criteria, compared with CEUS LI-RADS v2017, had significantly increased sensitivity (89% vs 69%, p<.001), a nonsignificant decrease in specificity (83% vs 87%, p>.99), and significantly increased accuracy (89% vs 71%, p<.001) for HCC. CONCLUSION. When using perfluorobutane for CEUS in at-risk patients, modified criteria incorporating Kupffer defects significantly improve sensitivity without significant loss of specificity in HCC detection. CLINICAL IMPACT. Future CEUS LI-RADS updates seeking to address the use of combined blood pool and Kupffer cell agents should consider adoption of the explored criteria.