CHAPTER 2 Ultrasound contrast agents (UCA) are now commercially available in Europe, Japan and the United States. They are intended and used for left ventricular opacification and for enhanced endocardial border delineation. The first-generations of contrast agents were composed of free air bubbles, whereas newer generations contain lessdiffusable gas cores with very flexible and soft envelopes. The new processes in bubble design had improved microbubble persistence significantly. In this chapter, nature and types of different contrast agents will be given. The focus will be on the composition and physical properties of current contrast bubbles and those under clinical trials or developments. The section ends with an outline of the role as well as the acoustic properties of gas bubbles. Description and characteristics of a blood pool UCA Contrast agents used for ultrasound imaging consist of gaseous microbubbles stabilized, or not, by a shell of biocompatible material, such as protein, lipid or polymer. The bubbles are smaller than red blood cells and are, therefore, appropriate for injection intravenously (IV). Unencapsulated free gas bubbles were first used as ultrasound contrast agents as early as 1968 (Gramiak and Shah 1968), but proved to be unsatisfactory because their size was uncontrolled, inappropriate and unstable. Once injected, they did not persist long enough in the circulation to permit an adequate ultrasound examination of the left side of the heart (Ophir and Parker 1989). Since these agents are intended to image the left heart chambers and, ultimately, to assess the perfusion of the myocardium, they must fulfill certain requirements. The contrast microbubbles should be administered IV, either by bolus or infusion. The microbubbles must be small enough and stable enough to insure a pulmonary passage. In addition, they must be injected in a sufficient concentration to opacify the left heart. Furthermore, the injected microbubbles should remain in the blood pool and be safe and nontoxic. The duration and persistence of the microbubbles should be comparable with that of imaging conditions to enable acquisition of echo images. To behave as a perfect blood pool, the microbubbles should display the same flow dynamics as the blood itself and ultimately be metabolized from the blood pool. To comply with these requirements, several bubble physical properties must be chosen carefully. These properties include the size, the gas and the shell. In addition, the effects of surrounding temperature and hydrostatic pressure on contrast gas bubbles are important.