“Hot Topics” in Contrast-Enhanced Ultrasound (CEUS) – Introduction

On the occasion of WFUMB 2011, the 13th World Congress of the World Federation for Ultrasound in Medicine and Biology (WFUMB), held in conjunction with the 35th Dreiländertreffen – ULTRASCHALL 2011, the 35th joint meeting of the Austrian, German and Swiss Societies for Ultrasound in Medicine and EUROSON 2011, the 23 rd Congress of the European Federation of Ultrasound in Medicine and Biology (EFSUMB), taking place in Vienna at the end of August 2011, both WFUMB and EFSUMB presented “The WFUMB/EFSUMB Liver Contrast-Enhanced Ultrasound (CEUS) Guidelines” and “The EFSUMB Guidelines and Recommendations on the Clinical Practice of CEUS: Update 2011 on Non-Hepatic Applications” [1]. CEUS was one of the “hot topics” of the scientific and educational program of WFUMB 2011.

The Bracco company, vendor of the US contrast agent sulfur-hexafluoride (SonoVue^®, Bracco, Milan, IT), supported a special symposium on “hot topics in contrast-enhanced ultrasound” at WFUMB 2011. After a number of months of re-defining certain topics and focusing not only on current guidelines but also on emerging and future applications of CEUS, the objective of this supplement to UiM/European Journal of Ultrasound is to inform both the CEUS expert and novice of recent advances, comments on current guidelines, controversies and future aspects of CEUS. This includes 7 articles written by experts, covering hepatic as well as non-hepatic CEUS applications [2] [3] [4] [5] [6] [7] [8]. This introduction focuses on certain aspects with the purpose of directing interested readers.

First, “off-label” use of the contrast agent sulfur-hexafluoride (SonoVue^®, Bracco, Milan, IT) occurs in many of the new non-hepatic applications and in pediatric US examinations. Ultrasound contrast agents registered in Europe are licensed only for cardiac or, in the case of SonoVue^®, for liver, breast and vascular applications [1]. This aspect has been covered in a recent editorial in UiM by P. S. Sidhu, B. I.Choi and M. B.Nielsen, representing an international faculty [9]. As stated there, “clearly the use of CEUS ‘off-label’ is of benefit to all our patients” [9]. Accordingly, the publication of “off-label” studies by researchers in the field of CEUS across the globe is going to increase further in the coming years. More studies on the use of CEUS in the trauma setting [10] [11], in the retroperitoneum including the adrenal glands [12] [13] [14] [15], in the musculoskeletal system [16], in the GI tract [17] [18] and in the chest [19] are going to be performed. Besides technical knowledge of CEUS as published in the recent guidelines, in-depth knowledge of CEUS pitfalls and artifacts are mandatory prerequisites [1] [20].

Second, as CEUS is now established as a valuable tool in many clinical applications, there is a scientific as well practical need to quantify parameters related to microbubble contrast enhancement. The lack of some form of “objective and reproducible” parameters in the early years of CEUS have been a significant drawback of CEUS compared to contrast-enhanced CT and MR, where perfusion parameters can be retrieved not only by visual analysis but also by objective measurements. Perfusion quantification seems to be mandatory for chemotherapy response evaluation using antiangiogenic therapy [21]. The article by CF Dietrich et al. [6] covers the theoretical background as well as practical aspects of perfusion quantification, and the article by F. Tranquart et al. [5] introduces US system-independent software for perfusion quantification. Accordingly, with a wider distribution of quantification software, CEUS might serve as a surrogate marker to predict response to antiangiogenic cancer therapy in various organs.

Third, endocavitary CEUS seems to have become a promising tool of another “off-label” application of ultrasound contrast agents [6] [22]. Although the precise concentration of US contrast has not been defined yet, adding some drops of SonoVue^® to a physiologic saline solution is all that is needed to outline fluid collections, to diagnose normal and abnormal connections between body cavities, to visualize bile duct obstructions and internal fistulae – and much more. Moreover, oral administration of contrast solutions seems to be suitable for diagnosing insufficient anastomoses of the GI tract and GI tract perforations [6] [22]. If large-scale, prospective studies support the results of early work in progress [6], some interventional guidance methods under fluoroscopy and the use of iodinated contrast can be replaced by bedside US with endocavitary and endoductal (biliary and urinary system) microbubble US contrast.

Finally, going back to where CEUS started, a major part of this supplement is focused on focal liver lesion detection and classification in the cirrhotic and non-cirrhotic patient [2] [3] [4] [7] [8]. Special emphasis is put on an ongoing discussion of the surveillance of hepatocellular carcinoma (HCC) in the cirrhotic liver. In 2010, the AASLD practice guidelines on the management of HCC removed CEUS from the diagnostic algorithm of HCC for lesions of any size, focusing on four-phase contrast-enhanced multidetector computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging (MRI) [23]. This guideline was recognized as “hostile fire” by many authorities in the US community [24]. Accordingly, this supplement includes two articles [7] [8] with a special focus on the impact of the availability of microbubble US agents worldwide on guidelines and recommendations and the problem of how to differentiate between small HCC and cholangiocellular carcinoma (CCC) in the liver [25].

Reading all of the articles in this UiM supplement will enhance your knowledge of CEUS in various organ systems and clinical settings. CEUS is an excellent, innovative technique requiring more distribution and application in the global US community. However, more high-quality, prospective studies are needed to fully appreciate this technique in comparison to state-of-the-art contrast-enhanced CT and MR, where appropriate. This supplement provides an excellent basis for new and innovative ideas and research projects on the application of CEUS.

Disclosure information: Gerhard Mostbeck has received lecture and consultant honoraria from the Bracco company in 2011 and 2012.

• References

• 1 Piscaglia F, Nolsoe C, Dietrich CF et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): Update on non-hepatic applications. Ultraschall in Med 2012; 33: 33-59
• 2 Dietrich CF, Maddalena ME, Cui XW et al. Liver Tumour Characterization – Review of the Literature. Ultraschall in Med 2012; Supplement
• 3 Dietrich CF, Cui XW, Ignee A. EFSUMB Guidelines 2011 – Comments and Illustrations. Ultraschall in Med 2012; Supplement
• 4 Dietrich CF. Liver Tumour Characterization – Comments and Illustrations on Guidelines. Ultraschall in Med 2012; Supplement
• 5 Tranquart F, Mercier L, Frinking P et al. Perfusion Quantification in Contrast-Enhanced Ultrasound – Ready for Research Projects and Routine Clinical Use. Ultraschall in Med 2012; Supplement
• 6 Dietrich CF, Cui XW, Barreiros AP et al. EFSUMB Guidelines 2011: Comment on Emergent Indications and Visions. Ultraschall in Med 2012; Supplement
• 7 Quaia E. The role of CEUS in the characterization of hepatocellular nodules detected during the US surveillance program – Current Practices in Europe. Ultraschall in Med 2012; Supplement
• 8 Dietrich CF, Cui WX, Boozari B et al. Contrast enhanced ultrasound in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma. Ultraschall in Med 2012; Supplement
• 9 Sidhu PS, Choi BI, Nielsen MB. The EFSUMB Guidelines on the NON-Hepatic Clinical Applications of Contrast Enhanced Ultrasound (CEUS): a New Dawn for the escalating Use of This Ubiquitous Technique. Ultraschall in Med 2012; 33: 5-7
• 10 Cokkinos D, Antypa E, Stefanidis K et al. Contrast-Enhanced Ultrasound for Imaging Blunt Abdominal Trauma – Indications, Descriptions of the Technique and Imaging review. Ultraschall in Med 2012; 33: 60-67
• 11 Dormagen J, Meyerdirks O, Gaarder C et al. Contrast-Enhanced Ultrasound of the Injured Spleen After Embolization – Comparison with Computed Tomography. Ultraschall in Med 2011; 32: 485-491
• 12 Friedrich-Rust M, Glasemann T, Polta A et al. Differentiation between Benign and Malignant Adrenal Mass using Contrast-Enhanced Ultrasound. Ultraschall in Med 2011; 32: 460-471
• 13 Friedrich-Rust M, Schneider G, Bohle RM et al. Contrast-enhanced sonography of adrenal masses: differentiation of adenomas and nonadenomatous lesions. Am J Roentgenol 2008; 191: 1852-1860
• 14 Dietrich CF, Ignee A, Barreiros AP et al. Contrast enhanced ultrasound for imaging of adrenal masses. Ultraschall in Med 2010; 31: 163-168
• 15 Mostbeck G. CEUS von Nebennierenraumforderungen – der Durchbruch?. Ultraschall in Med 2011; 32: 437-439
• 16 Loizides A, Widmann G, Peer S et al. Optimizing Ultrasound-Guided Biopsy of Musculo-skeletal Masses by Application of an Ultrasound Contrast Agent. Ultraschall in Med 2011; 32: 307-310
• 17 Girlich C, Jung EM, Huber E et al. Comparison between Preoperative Quantitative Assessement of Bowel Wall Vascularization by Contrast-Enhanced Ultrasound and Operative Macroscopic Findings and Results of Histopathologic Scoring in Crohn’s Disease. Ultraschall in Med 2011; 32: 154-159
• 18 Goertz RS, Heide R, Bernatik T et al. Mesenteric Transit Time Using Contrast-Enhanced Ultrasound (CEUS) Does Not Correlate with Disease Activity in Crohn’s Disease. Published online Ultraschall in Med 2011; DOI: http://dx.doi.org/10.1055/s-0031-1282064.
• 19 Linde HNG, Holland A, Greene BH et al. Kontrastunterstützte Sonografie (CEUS) bei Pneumonie: Darstellungsmuster und prognostische Bedeutung – eine retrospective Studie bei n=50 Patienten. Published online Ultraschall in Med DOI: http://dx.doi.org/10.1055/s-0031-1273280.
• 20 Dietrich CF, Ignee A, Hocke M et al. Pitfalls and artefacts using Contrast Enhanced Ultrasound. Z Gastroenterol 2011; 49: 350-356
• 21 Schirin-Sokhan R, Winograd R, Roderburg C et al. Response evaluation of chemotherapy in metastatic colorectal cancer by contrast enhanced ultrasound. World J Gastroenterol 2012; 18: 541-545
• 22 Heinzmann A, Müller T, Leitlein J et al. Endocavitary Contrast Enhanced Ultrasound (CEUS) – Work in Progress. Ultraschall in Med 2012; 33: 76-84
• 23 Bruix J, Sherman M. AASLD Practice Guideline: Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
• 24 Giorgio A. CEUS and HCC: Are the 2008 EFSUMB Guidelines Still Valid or has their Wash-out already started?. Ultraschall in Med 2011; 32: 315-316
• 25 Bohle W, Clemens PU, Heubach T et al. Contrats-Enhanced Ultrasound (CEUS) for Differentiating Between Hepatocellular abd Cholangiocellular Carcinoma. Published online Ultraschall in Med DOI: http://dx.doi.org/10.1055/s-0031-1282029.