New prospects for ultrasound contrast agents.

Considering the several suggestions regarding the future developments of echocontrast agents, there is a striking difference between the few compounds actually available on the market and used in clinical practice and those undergoing experimental clinical trials. It is therefore difficult to predict what will be the actual impact of these agents in the next future. Future developments will probably go beyond color enhancement which was the end-point till a very short time ago. They can be schematically summarized as follows: (1) development of new substances which enhance both color and gray scales; (2) use of new-generation substances, such as BR1 (Bracco, Milan, Italy) and EchoGen (Sonus, Bothell, WA), which use a gas other than air, such as perfluorate compounds which are more stable and guarantee longer and stronger effects; (3) use of more complex compounds acting at different levels. For example, SHU 536A (Sonovist) produces resonance phenomena with the second and third harmonics, and also stimulated acoustic emission which permits the morphological study of liver parenchyma. Other promising compounds are liposomes and aerosomes. Among the new possibilities in recording and observing phenomena, we can distinguish two main application fields: one is based on the physics of ultrasound and related to the presence of microbubbles in an acoustic field. These phenomena are generally obtained increasing the emission acoustic pressure, which eventually results in microbubble destruction and they are called nonlinear because there is no direct relationship between emission and return frequencies. These phenomena, which are detectable only with dedicated equipment, include: the resonance phenomenon with harmonic emission; intermittent harmonic emission and stimulated acoustic emission. The other application field is not strictly related to ultrasound physics and includes all the systems which can detect the presence of microbubles qualitatively or quantitatively. Other possible applications are related to the possibility of acquiring not only morphological but also functional data, especially in cardiology and neurology. Finally, targeted agents are potentially capable of demonstrating receptor sites or specific molecules, which may open very interesting therapeutic routes.