Breakthrough Imaging in Hepatocellular Carcinoma

The ultrasound (US) contrast agent, SonoVue®, has been approved for use worldwide. Conversely, Sonazoid®, which was approved in Japan ahead of other countries in January 2007, is also currently used in Korea, China, and Norway, although its use is gradually spreading to other countries. Sonazoid®-enhanced US is considered a breakthrough imaging technology because it has drastically changed clinical practice, especially in the treatment of hepatocellular carcinoma (HCC) [1, 2]. Sonazoid®-enhanced US imaging is divided into two phases, namely the vascular and Kupffer phases, based on the in vivo dynamics of the agent. Sonazoid®-enhanced US is extremely sensitive for the detection of intranodular blood flow in hepatic tumors, and it is superior to the sensitivity of triphasic multidetector-row computerized tomography (MDCT) [3]. In other words, contrast-enhanced US (CEUS) detects arterial blood flow in real time, resulting in 100% sensitivity. This means that the detection sensitivity of CEUS for intranodular arterial blood flow is higher than that of MDCT. It is also well known that CT hepatic angiography (CTHA), in which CT and angiography are performed concurrently, is inferior to CEUS in terms of the detection sensitivity for intranodular arterial blood flow. SonoVue® -enhanced US is normally performed to display intranodular blood flow for a thorough examination of previously detected nodules by B-mode US. However, unlike SonoVue®, the Kupffer phase of Sonazoid®-enhanced US is used to survey the entire liver by depicting Kupffer defects. Intranodular vascularity is subsequently detected by re-injecting Sonazoid® (defect reperfusion imaging) [2, 4], thus enabling the concurrent detection and definitive diagnosis of HCCs. Accordingly, Sonazoid®-enhanced US can be used for visualizing B-mode ill-defined nodules as well as for surveillance and staging, which is not feasible with CEUS using SonoVue®. The Kupffer phase of Sonazoid®-enhanced US is an extremely important phase for the following reasons: (1) All hypervascular HCCs are well-to-moderately differentiated HCCs, and thus show decreased or absent Sonazoid® uptake in the Kupffer phase. (2) Among precancerous lesions such as dysplastic nodules (DNs) and early HCCs [5], those with a poor arterial blood supply, but with a preserved portal venous supply, appear isoecho© 2015 S. Karger AG, Basel 2235-1795/16/0051-0047$39.50/0 www.karger.com/lic Liver Cancer 2016;5:47–54