Background: It remains unknown whether Kupffer-phase images in Sonazoid-enhanced ultrasonography (US) can be used to predict hypervascularization of borderline lesions. Therefore, we aimed to clarify whether Kupffer-phase images in Sonazoid-enhanced ultrasonography can predict subsequent hypervascularization in hypovascular borderline lesions detected on hepatobiliary-phase gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging.
Methods: From January 2008 to March 2012, 616 low-intensity hypovascular nodules were detected in hepatobiliary-phase images of Gd-EOB-DTPA-enhanced MRI at nine institutions. Among these, 167 nodules, which were confirmed as hypovascular by Gd-EOB-DTPA-enhanced MRI and Sonazoid-enhanced US, were evaluated in this study. Potential hypervascularization factors were selected based on their clinical significance and the results of previous reports. The Kaplan-Meier model and log-rank test were used for univariate analysis and the Cox regression model was used for multivariate analysis.
Results: The cumulative incidence of hypervascularization of borderline lesions was 18, 37, and 43 % at 1, 2, and 3 years, respectively. Univariate analyses showed that tumor size (p = 0.0012) and hypoperfusion on Kupffer-phase images in Sonazoid-enhanced US (p = 0.004) were associated with hypervascularization of the tumor. Multivariate analysis showed that tumor size [HR: 1.086, 95 % confidence interval = 1.027-1.148, p = 0.004] and hypo perfusion on Kupffer-phase images [HR: 3.684, 95 % confidence interval = 1.798-7.546, p = 0.0004] were significantly different.
Conclusions: Kupffer-phase images in Sonazoid-enhanced US and tumor diameter can predict hypervascularization of hypointense borderline lesions detected on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI.
Keywords: Gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid-enhanced MRI; Hepatocellular carcinoma; Hypervascular transformation; Kupffer phase; Sonazoid-enhanced ultrasonography.