Differential Diagnosis of Hepatic Tumors: Value of Contrast-Enhanced Harmonic Sonography Using the Newly Developed Contrast Agent, Sonazoid

Abstract

Objective: To clarify the value of contrast-enhanced harmonic ultrasonography (US) with Sonazoid, a second-generation US contrast agent, in the differential diagnosis of liver tumors compared to dynamic CT. Methods: A total of 249 hepatic nodules in 214 patients were studied; these included 177 hepatocellular carcinomas (HCCs), 42 liver metastases, 20 liver hemangiomas, 6 dysplastic nodules and 4 focal nodular hyperplasias (FNHs). After the injection of Sonazoid, nodules were scanned using real-time contrast-enhanced harmonic US in the vascular phases, i.e. the early and late vascular phases, and the Kupffer phase. Results: Six enhancement patterns were identified to be significant for the differential diagnosis of hepatic tumors. In HCCs, the presence of intratumoral vessels supplied from the periphery and fast washout (sensitivity, 96.6%; specificity, 94.4%) were the most typical characteristics. In metastases, the presence of rim-like enhancement with peripheral tumor vessels (sensitivity, 88.1%; specificity, 100%) was the typical pattern. In hemangiomas, the presence of intratumoral hypoperfusion images with globular or cotton wool-like pooling, which continue to the late vascular phase (sensitivity, 90.0%; specificity, 99.6%), was typical. In dysplastic nodules, the presence of portal enhancement without arterial supply in the early vascular phase and the presence of intratumoral uptake in the Kupffer phase (sensitivity, 83.3%; specificity, 100%) were the most typical patterns. In FNHs, the presence of a spoke-wheel pattern in the early vascular phase with dense staining in the late vascular phase, and positive uptake within the nodule in the Kupffer phase (sensitivity, 100%; specificity, 100%) were the most typical patterns. Conclusion: Contrast-enhanced harmonic US with Sonazoid allowed intimate vascular and Kupffer imaging and, therefore, is useful for the differential diagnosis of hepatic tumors.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Hatanaka et al [189] reported that intranodular vascularity was detected in 99.4% of HCCs on contrastenhanced, harmonic US. In the remaining 0.6% of HCCs, no blood signal was detected.…”

“…CEUS is more sensitive for detecting arterial vascularity of target nodules than dynamic CT or dynamic MRI [189,243]. Thus, hypovascular nodules on dynamic CT may be diagnosed by CEUS.…”

“…Addition of the postvascular phase (Kupffer phase) allows an assumption of the degree of malignancy based on Kupffer function [189,225,244].…”

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

“…Sonazoid is another second-generation UCA solely available in Japan. Sonazoid consists of perfluorobutane microbubbles with a median diameter of 2 to 3 μm [17] . A pharmacokinetic study of Sonazoid showed that blood concentrations of perfluorobutane declined biphasically with a distribution half-life of 2 to 3 min and an elimination half-life of 30 to 45 min [18] .…”

“…The new UCA Sonazoid provides Kupffer imaging, which is extremely stable and tolerable for multiple scanning at least up to 60 min in the post-vascular phase, and may further improve the detection rate of HCC with CEUS [41] . The analysis of Kupffer function provides essential information compared with other contrast agents [17,42] . CEUS with Sonazoid detects liver malignancy as defects on the sinusoidal phase with a high sensitivity of 95%, specificity of 93%, positive predictive value of 99%, and negative predictive value of 97% [43] .…”