A Milestone: Approval of CEUS for Diagnostic Liver Imaging in Adults and Children in the USA

Abstract

The approval of microbubbles with the inert gas sulfur hexafluoride (SF6) and a palmitic acid shell (SonoVue(®), Bracco Geneva, CH) for the diagnostic imaging of liver tumors in adults and children by the FDA in the United States represents a milestone for contrast-enhanced ultrasound (CEUS).This warrants a look back at the history of the development of CEUS. The first publications based on echocardiographic observations of right ventricular contrast phenomena caused by tiny air bubbles following i. v. injection of indocyanine green appeared around 1970 1 2 3. A longer period of sporadic publications but no real progress then followed since, in contrast to X-ray methods, ultrasound works quite well without a contrast agent.It is noteworthy that the foundations for further development were primarily laid in Europe. The development and approval (1991) of the contrast agent Echovist(®) by a German contrast manufacturer for echocardiography unsuitable for passing through lungcapillaries 4 5 resulted in the first extracardiac indications, e. g. for detecting retrovesical reflux and tubal patency, in the mid-1980 s 6 7 8. The sensitivity of color Doppler was not able to compensate for the lack of an ultrasound contrast agent compared to CT with its obligatory contrast administration.Studies of SHU 508 - microbubbles of air moderately stabilized with galactose and palmitic acid - began in 1990 9 10 11 12 13 14 15 and the contrast agent was then introduced in 1995 in Germany as Levovist(®). The most important publications by Blomley, Cosgrove, Leen, and Albrecht are named here on a representative basis 16 17 18 19 20.SHU 508 along with other US contrast agents provided impressive proof of the superiority of CEUS for the diagnosis of liver metastases. However, practical application remained complicated and required skill and technical know-how because of a lack of suitable software on US units 21 22 23 24 25. The monograph regarding the use of contrast agent in the liver by Wermke and Gaßmann is impressive but unfortunately only available in German 26. In addition to being applied in the heart and the liver, CEUS was first used in transcranial applications 27 and in vessels 28, the kidneys 29, and the breast 30. Measurements at transit times were also of particular interest 31. It was difficult to convince ultrasound device manufacturers of the need to adapt US units to US contrast agents and not vice versa.The breakthrough came with low MI phase contrast inversion and the introduction of SonoVue(®) in many European countries in 2001. This more stable US contrast agent is easy to use and is becoming indispensable in diagnostic imaging of the liver 32 33 34 35 36 37 38 39 40. Studies have shown its excellent tolerability 41 and diagnostic reliability comparable to that of MDCT and MRI in the liver 42 43. Today it would be unimaginable to diagnose liver tumors without CEUS 44. This also applies to very small lesions 45 46.EFSUMB published the first CEUS guidelines in 2004 47 which have since been reissued and divided into h...

Clinical Applications of Contrast-Enhanced Ultrasound in the Pediatric Work-Up of Focal Liver Lesions and Blunt Abdominal Trauma: A Systematic Review

“…Until now the majority of CEUS research has been performed in Europe. However, this seems likely to change [7]. According to the manufacturer, the dosage of Lumason ® is weight-dependent at 0.03 mL per kg with a maximum of 2.4 mL per injection and may be repeated once [8].…”

Evaluation of the Value of Contrast-Enhanced Ultrasound (CEUS) within Radiology Departments in Germany

“…However, parents are informed of this situation during the informed consent discussion in the majority of cases. The FDA recently approved CEUS for diagnostic liver imaging in children in the USA [10]. Approval of CEUS in pediatric diagnostic imaging can also be expected in Europe.…”

“…The FDA recently approved CEUS for diagnostic liver imaging in children in the USA [10]. In the long term, insufficient use of this method in radiology would result in the diagnostic spectrum of the radiology discipline being incomplete [8,11].…”

Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis and β-cell mass decline in mouse models of type 1 diabetes

“…Contrast-enhanced ultrasound (CEUS) utilizes lipid-or protein stabilized gas core microbubbles (MBs) that provide a strong acoustic backscatter of ultrasonic waves. MBs are FDA approved for cardiac and liver imaging in adult and pediatric populations 20 , and have been used 'off label' for other indications 21,22 . While MBs are restricted to the blood stream, smaller sub-micron sized nanobubbles (NBs) are capable of extravasating through the hyper-permeable microvasculature of injured tissue.…”