Contrast enhancing agents in ultrasonography: clinical applications

As ultrasound remains a poorly sensitive method, echocontrast agents make a real difference. At least 29 echocontrast agents are currently on trial worldwide; their chemical composition, mechanisms of action and possible clinical applications are different. The state of the art of echocontrast agents is discussed: their established applications, those expected in the near future and finally their hypothetical, ideal applications.

An extravascular and a vascular domain can be considered. The former includes the gastrointestinal tract and body cavities--both the normal (bladder, uterus, tubes and so on) and the abnormal (abscesses, fistulas, pericardium, peritoneum and so on) ones. Echocontrast agents can: (1) create or improve an acoustic window; (2) distend some organs and fill them with a liquid, with homogenous attenuation of the ultrasound beam; (3) displace the air-containing intestinal loops; (4) depict the walls, the shape and the contours of a normal or abnormal cavity; (5) detect abnormal communications, fistulas and drainages; and (6) evaluate the amount of fluid in the pleural, pericardial or peritoneal cavities. As for vascular applications, this domain sees the highest number of echocontrast agents on trial or on the market. The best know of them are: Levovist (Schering AG, Berlin, Germany), BR1 (Bracco, Milan, Italy) and EchoGen (Abbott, USA). All these act by enhancing arteries, veins and capillaries. The clinical applications validated in clinical trials mainly regard studies in intracranial and neck vessels and the vascularity of upper and especially lower limbs of renal vessels. Tumor macrovascularity (and in the future, hopefully microvascularity) can also be studied in parenchymatous and/or glandular organs, as well as in intra- and extra-abdominal parenchymatous organs in the periskeletal soft tissues. Clinical validation has also been obtained in the follow-up of tumors submitted to ablation therapy (chemoembolization, ethanol injection, thermal ablation) and in echocardiography, both for morphological studies in the cardiac cavities and for the cardiac wall perfusion.

In a subgroup of 513 out of 1275 patients examined Europe-wide, the contrast agent Levovist increased the diagnostic confidence from 27.4 +/- 22.5 to 77.2 +/- 22.5%. Such data encourage further trials to validate current preliminary results.