Improved Detection of Liver Metastases with Phase Inversion Ultrasound During the Late Phase of Levovist

Abstract

The sensitivity of ultrasound (US) in the detection of liver metastases ranges between 53% and 84% (1,2); thus, US is inferior to computed tomography (CT) and magnetic resonance imaging (MRI) in this application. Most lesions missed on US are either small—the sensitivity for detecting lesions 1 cm is only 20% (1)—or near-isoechoic and, thus, mainly reflect the relatively poor contrast between lesion and normal liver parenchyma. It was recently shown that the US contrast agent Levovist (Schering AG, Berlin, Germany), which was developed to enhance Doppler signals in technically difficult vascular studies, accumulates in liver parenchyma during a late liver-specific phase (3). This follows after the agent’s blood pool phase and starts approximately 2.5 min after an intravenous (IV) bolus injection. It lasts approximately 30 min provided no bubble destruction has occurred due to earlier scanning (4,5). The late-phase contrast effect is specific to normal liver (and spleen) parenchyma and spares focal lesions such as metastases (3,5,6). The increase in backscatter provided by Levovist is not sufficient to obtain late-phase liver enhancement on conventional (fundamental) B-mode US. This requires highly sensitive microbubble-specific imaging techniques that use the nonlinear (ie, distorted) signals that are returned from microbubbles when scanning at high transducer output (still within the range of diagnostic US). In the case of Levovist, stimulated acoustic emission (SAE) is the most important nonlinear phenomenon in this context. SAE is a process of bubble destruction caused by the insonating US beam, which produces a characteristic, strong, transient, nonlinear signal of a wide frequency range (7,8). So far, SAE enhancement of liver parenchyma has been mainly imaged using velocity-encoded color Doppler US, in which the wide frequency range of the returned SAE signal is interpreted by the scanner as a “pseudo Doppler shift” and, thus, displayed as a characteristic dense color mosaic with a range of velocities randomly distributed in the liver parenchyma. This color mosaic spares focal lesions such as metastases and markedly improves lesion-to-liver contrast. In a preliminary series of 19 patients with liver metastases, Blomley and associates compared color SAE imaging during the late phase of Levovist with conventional B-mode US. The authors found not only that SAE imaging improved lesion conspicuity in all cases but it also detected three additional metastases (6). However, this color technique suffers from several limitations: The enhancement effect is limited to the color box, and temporal as well as spatial resolution is inferior to B-mode US. Furthermore, the enhancement is encoded as “yes or no” information (color present or absent), which can make image interpretation difficult especially with regards to artifacts. We recently presented the first human results of a new, highly sensitive, microbubble-specific US technique called Acad Radiol 2002; 9(suppl 1):S236–S239