Liver Metastases: Sulphur Hexafluoride–Enhanced Ultrasonography for Lesion Detection: A Systematic Review

Abstract

This is a systematic review to evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) performed with “SonoVue” (sulphur hexafluoride) in the detection of hepatic metastases. The MEDLINE, EMBASE and COCHRANE Databases were searched, regardless of language, for relevant articles published before December 2009. Two reviewers independently assessed study eligibility using a standardized form and methodological quality using the quality assessment of diagnostic accuracy studies (QUADAS) Checklist. Sensitivity estimates were calculated on a per-patient and/or per-lesion basis. The search for published articles yielded 718 potentially relevant abstracts. Of these, 14 papers were eligible but only three articles fulfilled the inclusion criteria, which comprised a total of 450 patients (patient sample number: range 12 to 365; cancer prevalence: 14.8 to 71.2%). Estimated per-patient sensitivity ranged from 79–100%. Although the quality assessment of diagnostic accuracy studies checklist showed the papers were of good quality, a meta-analysis was not applicable because of the lack of eligible studies. In conclusion, CEUS seems to be promising in the detection of liver metastases; however, there have not been enough studies to conduct meta-analysis. Further studies are required before this promising method can be widely used. (E-mail: [email protected])

Introduction

In patients with known primary tumor, B-mode ultrasonography (US) is a valuable, first screening tool for liver lesion detection. However, sensitivity of US in both primary and metastasis detection is low and variable, ranging from 50–76% for metastasis (Albrecht et al., 2004, Cosgrove and Bolondi, 1993, Glover et al., 2002) and 51–91% for primary liver tumors (Charatcharoenwitthaya et al., 2008, Schneider et al., 1999, Teefey et al., 2003).

Contrast-enhanced ultrasonography (CEUS) has recently changed the way of performing ultrasound examinations (Leen et al., 2004, Nicolau and Brú, 2004) and has apparently increased the possibility to detect more metastases compared with B-mode scanning (Lencioni et al., 2007, Solbiati et al., 2001). With CEUS, it is possible to characterize focal liver lesions with patterns of enhancement similar to contrast-enhanced multi-detector computed tomography (MDCT) and magnetic resonance imaging (MRI) with higher than 90% accuracy (Cosgrove, 2007, Lencioni et al., 2007, Solbiati et al., 2001).

Early published papers focused on so called “first-generation” contrast media, with good results in terms of sensitivity and specificity. In particular, multicenter or single-center studies reported lesion detection sensitivity ranging from 87–91% (Albrecht et al., 2001, Albrecht et al., 2003, Blomley et al., 1999).

Despite this positive experience, “first-generation” contrast media had some limitations, including overly rapid transient effect because of instant microbubble destruction after insonation and lack of penetration.

These drawbacks led to the development of “second-generation” contrast media. In particular, SonoVue (Bracco, Milan, Italy) microbubbles are filled with sulfur hexafluoride (SF6), a gas with a low solubility and a great stability and resistance to pressure. Because of the high flexibility of their shell, sulfur hexafluoride microbubbles are strongly echogenic at a wide range of frequencies and acoustic pressure and can therefore be used with both destructive and, more importantly, conservative contrast bubble–specific imaging methods (Lencioni et al. 2002). With the low mechanical index (MI) technique, it is possible to scan the liver in real time during arterial, portal, or late phases, without a significant loss of signal, thus raising the capability of detecting liver lesions (Claudon et al., 2008, Nicolau et al., 2003).

The value of CEUS in liver metastasis detection has been reported by recent reviews and by international guidelines (Albrecht et al., 2004, Claudon et al., 2008, Hohmann et al., 2004, Konopke et al., 2007b). Nevertheless, the diagnostic value of this technique in patients with known neoplasms is still not clear. The key question is whether CEUS should be performed routinely in patients with known neoplasms to detect metastases. The aim of our study was to perform a systematic review of the capability of CEUS in the detection of liver metastases.