Medical Device Daily

PARIS — While contrast enhanced ultrasound (CEUS) remains an off-label use beyond cardiac applications in the United States, European physicians are rapidly compiling a powerful clinical case for applying the technique for tumor detection and tissue characterization almost everywhere else in the body.

In August, CEUS was recommended by the UK's National Institute for Health and Clinical Excellence (NICE) for the detection of focal liver lesions, for characterizing cirrhosis, for investigating potential liver metastases.

NICE is Europe's only methodic health technology assessment authority and both is widely followed and highly influential with its sharp eye for opinions on cost-effectiveness.

At this time last year, the European Federation of Societies in Ultrasound Medicine and Biology (EFSUMB; London) issued guidelines on Liver CEUS as well as recommendations on non-hepatic applications.

This week, gastrointestinal CEUS is a thematic focus for scientific sessions at Ultraschall-Dreiländertreffen, the annual Three Countries Ultrasound Meeting, in Davos, Switzerland.

The three countries for the all-German congress are Austria, Germany and Switzerland.

The 2012 congress president André Dietschi from the Santémed Health Center (Winterthur, Switzerland), told European Hospital that where recent technical developments in ultrasound have been less than revolutionary, developments in contrast agents are far more exciting.

“Emerging expertise about their effects and potential areas of application have attracted significant attention,“ he said. “There are basically no restrictions to experimenting in new areas of application because the contrast agent will cause no harm, while the potential benefits are significant.“

While several companies are advancing CEUS agents toward the market, notably Sonozoid from GE Healthcare (Waukesha, Wisconsin), the dominant agent in clinical practice in Europe is SonoVue from Bracco Diagnostics (Milan, Italy) that has been available since 2001 in Europe.

The approval of CEUS in the U.S. remains fixed at the FDA approval for cardiac imaging in patients with suspected or established cardiovascular disease to improve visualization of cardiac chambers and endocardial borders.

In Europe SonoVue is approved for liver, breast and vascular applications.

An aqueous suspension of microbubbles in the blood will enhance the ultrasound signal, illuminating a target area.

The distinguishing quality of SonoVue is the use of sulfur-hexafluoride microbubbles that Bracco claims further amplifies the signal quality yielding diagnostic information comparable to more expensive imaging techniques such as nuclear medicine, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI).

Bracco reported to the FDA in March 2011 that the database of pooled data on SonoVue for 70 completed clinical includes 5,275 patients with only three patients reporting adverse events where the contrast agent could not be ruled out as the cause.

In the 18 months since that report, the database of clinical studies has grown rapidly.

European clinicians have a long advance on American colleagues for exploring every aspect of a CEUS examination from transducers to dosage.

A special supplement to the European Journal of Ultrasound (Ultraschall in der Medizin) ahead of this week's Three Country Meeting in Davos covers topics such as perfusion quantification, nodules characterization, and the range of developing diagnostic algorithms.

The mathematical models used to extract the visualization from the ultrasound signal becomes critical to bring perfusion quantification with CEUS to the standards established for contrast enhancement with CT and MRI.

Time intensity curve parameters emerging as essential criteria for CEUS diagnosis include especially the wash-in/wash-out analysis with bolus injection.

The recent European CEUS guidelines provide researchers with detailed discussion of these models, including pitfalls and artifacts that can be encountered.

Off-label usage by researchers in Europe is overtly encouraged by not only by Three Country Meeting president Dietschi but also the editors of the European Journal of Ultrasound who wrote in the August, 2012 supplement that CEUS presents a promising tool for studies in the musculoskeletal system, the gastrointestinal tract and in the chest.

As an example they cite explorations for endocavitary.

“Although the precise concentration of ultrasound 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,“ they wrote.

Three years ago Bracco and TomTec (Munich, Germany) introduced SonoLiver, a PC-based software for radiologists to review off-line dynamic images of blood perfusion in the liver (Medical Device Daily, March 18, 2009).

The number of clinical studies for liver focal lesions jumped following the availability of the software on original equipment manufacturers platforms.

At Davos, discussion will build around the especially disruptive finding using dynamic contrast-enhanced ultrasound (DCE-US) that is proving to be a rapid, low-cost, safe and repeatable method for assessing the effectiveness of chemotherapies.

A consensus paper on DCE-US published in the journal European Ultrasound is led by Europe's most-published author on CEUS, Christoph Dietrich, MD, the current president of European Federation of Societies in Ultrasound Medicine and Biology (EFSUMB).

Co-author Nathalie Lassau, MD, from the prestigious Institute Gustave Roussy (Paris) is a pioneer of the technique who demonstrated in a multicenter study that DCE-US combined with a quantitative assessment of solid tumor perfusion using raw linear data could determine within two weeks of the start of treatment the effectiveness of 15 different antiangiogenic drugs across multiple types of cancers (MDD, Oct. 28, 2010). The cost of the exam using two bolus injections of SonoVue is €182 ($254).

Identifying non-responders in the first month of treatment could prevent patients from enduring a further five months of treatment and save healthcare systems an estimated $40,000 per patient.