Characterization of Tumor Imaging with Microbubble-Based Ultrasound Contrast Agent, Sonazoid, in Rabbit Liver

Abstract

Ultrasonography (US) is useful for diagnosis of hepatic focal lesions, which is based on their distinctive echogenicities; the gray-scale morphologic features. To improve diagnostic ability of detection and characterization of tumors, contrast imaging has been used in diagnostic imaging, e.g. X-ray computed tomography (CT) or magnetic resonance imaging (MRI), but has not yet been popular in US since contrast agents for US are not at clinical satisfaction level. Intravenous US contrast agents available for clinical use or the agents under development are basically microbubbles whose size is comparable to or less than red blood cells. First-generation agent consisted of air-microbubbles, Levovist (SH U 508A; Schering, Berlin, Germany), is commercially available in many countries, 1-6) but short imaging duration and weak contrast effect due to instability of the microbubbles could provide only limited diagnostic information.1,2) In order to improve the contrast effects, second-generation agents that use less soluble gases for microbubbles are being developed and now clinically available in limited western countries.1,6-9) Viewpoint from US imaging machine, to detect microbubbles more sensitively, harmonic imaging technology has been developed to visualize the harmonic echo from the microbubbles: backscatter signal (echo) from the microbubbles contains more harmonic component than that from tissues. 1)One of the second-generation agents, Sonazoid (previously NC100100, Amersham Health, Oslo, Norway) 7,10) has been reported to enhance perfusion of the myocardium and other organs. 7,[11][12][13][14] In the previous study, 15) we have characterized contrast enhancement of Sonazoid on the liver of metastatic carcinoma-model (VX-2) in rabbits, 16,17) and demonstrated promising contrast effect on the detection and delineation of liver tumors. This is due to uniqueness of Sonazoid whose microbubbles are likely to be taken up by Kupffer cells (liver macrophages) in the healthy liver and enhances contrast of the liver parenchyma during the delayed phase, which usually occurs within 10 min after the injection. In contrast, tumor that lacks Kupffer cells was not enhanced resulting in clear negative contrast of the tumor.In the previous study, comparison of the tumor contrast with histopathology of the tumors could not be examined in detail, since resolution of US images that had been acquired using the harmonic imaging technique was not enough to compare with microscopic images. To improve resolution and signal-to-noise ratio of this harmonic technique, phase inversion imaging (PII) technique was then developed and now become available in the commercial US machine. 6,18,19) PII can detect harmonic echoes from the microbubble contrast agent with greater sensitivity and without the loss of spatial resolution often seen in the harmonic imaging.Localization of the microbubbles in the liver Kupffer cells has been demonstrated in rat by using transmission electron microscopy (TEM). 20) However, the liver contrast effect in rats, such...

Effect of treatment support on preventing local recurrence of hepatocellular carcinoma directly adjacent to the diaphragm

“…The target lesions were scanned following injection in the arterial and Kupffer phases. The arterial phase of CEUS imaging was defined as that which occurred from 10-60 sec following the injection of Sonazoid™, and the Kupffer phase as that occurring 10 min following injection (10,12).…”

Clinical translation in the treatment of hepatocellular carcinoma following the introduction of contrast-enhanced ultrasonography with Sonazoid

“…the target lesions were scanned following injection in the arterial and Kupffer phases. The arterial phase of CEUS imaging was defined as that which occurred from 10 to 60 sec after injection of sonazoid, and the Kupffer phase as that occurring 10 min after injection (19). Fifteen frames/sec were usually used to scan for a low mechanical index (0.2-0.3).…”

Assessment of hepatocellular carcinoma by contrast-enhanced ultrasound with perfluorobutane microbubbles: comparison with dynamic CT

“…Levovist (Schering AG, Berlin, Germany) is a first-generation contrast agent widely used to characterise focal liver lesions [8][9][10][11][12]. The advent of Sonazoid, a second-generation contrast agent (perfluorobutane; Diichi Sankyo, Tokyo, Japan), enables low mechanical index continuous real-time imaging and Kupffer imaging [13][14][15]. Therefore, contrast-enhanced ultrasound (CEUS) using Sonazoid could potentially offer high-quality, detailed vascular information and clearer Kupffer imaging.…”