The second generation ultrasound contrast agents (UCA/USCA) are both sufficiently small and stable to pass into the systemic circulation, and these contrast media enhance the Doppler signal in various arteries after intravenous injection. Second generation agents have a short live, the contrast effect is over in a few minutes.

The earliest introduction of vascular ultrasound contrast agents (USCA) was by Gramiak and Shah in 1968, when they injected agitated saline into the ascending aorta and cardiac chambers during echocardiographic to opacify the left heart chamber. Strong echoes were produced within the heart, due to the acoustic mismatch between free air microbubbles in the saline and the surrounding blood.
The disadvantage of this microbubbles produced by agitation, was that the air quickly leak from the thin bubble shell into the blood, where it dissolved. In addition, the small bubbles that were capable of traversing the capillary bed did not survive long enough for imaging because the air quickly dissipated into the blood. Aside from agitated saline, also hydrogen peroxide, indocyanine green dye, and iodinated contrast has been tested. The commercial development of contrast agents began in the 1980s with greatest effort to the stabilization of small microbubbles.

The development generations by now:
To pass through the lung capillaries and enter into the systemic circulation, microspheres should be less than 10 μm in diameter. Air bubbles in that size range persist in solution for only a short time; too short for systemic vascular use.
The first developed agent was Echovist (1982), which enabled the enhancement of the right heart. The second generation of echogenic agents, sonicated 5% human albumin-containing air bubbles (Albunex), were capable of transpulmonary passage but often failed to produce adequate imaging of the left heart. Both Albunex and Levovist utilize air as the gas component of the microbubble.
In the 1990s newer developed agents with fluorocarbon gases and albumin, surfactant, lipid, or polymer shells have an increased persistence of the microspheres. This smaller, more stable microbubble agents, and improvements in ultrasound technology, have resulted in a wider range of application including myocardial perfusion.

See also First Generation USCA, Second Generation USCA, and Third Generation USCA.

From GE Healthcare;;
Optison is the first 'second generation USCA' marketed in the US.
Ultrasound contrast agents used during an ultrasound imaging procedure, enable more accurate diagnosis of the patient's heart condition. The application of Optison allows to image the endocardial borders of the heart, to see cardiac wall motion abnormalities and to guide the selection and monitoring of treatment.
Optison represents a class of microbubbles with a shell formed by sonicating a solution of capsules filled with a perfluoropropane gas. The high molecular weight slows microbubble dissolution and prolongs the enhancement for several minutes. The human albumin-stabilized cavitation bubbles have a surface tension of 0.9 N/m and a surface dilatational viscosity 0.08 msP.

'August 06, 2001 Molecular Biosystems Inc., a subsidiary of Alliance Pharmaceutical Corp, announced the amendment of the Optison Product Rights Agreement (OPRA) dated May 9, 2000 with Mallinckrodt Inc, a unit of Tyco Healthcare. Optison, an intravenous ultrasound contrast agent, was developed by MBI and is being marketed by Mallinckrodt in the U.S. and Europe. Under the amended agreement, MBI will receive an immediate cash payment plus additional unspecified royalties for a two-year period. The amendment of OPRA coincides with an announcement by Nycomed Amersham Imaging that Nycomed and Mallinckrodt will terminate their joint commercialization and development agreement for ultrasound contrast agents, including Optison, effective Dec. 31, 2001. Effective Jan. 1, 2002, all selling and marketing activities will be resumed solely by Nycomed Amersham.'

SonoGen (QW7437) is an anionically charged 2% perfluorocarbon emulsion under development as a transpulmonary myocardial ultrasound contrast agent (UCA). The SonoGen microbubbles have a reduced adherence to the negatively charged vascular endothelium and reduced coalescence. SonoGen, a second generation USCA has the theoretical potential to provide high safety and efficacy and improved tissue grayscale persistence compared to first generation fluorocarbon contrast agents.

From Bracco Diagnostics, Inc.
SonoVue® was first launched in October 2001 and is now available in all European countries.
SonoVue is a second generation USCA, designed and optimized with regard to the resistance to pressure. SonoVue is an example of an important family of microbubbles whose membrane consists of phospholipids. SonoVue microbubbles are filled with sulfur hexafluoride (SF6), a gas which has a low solubility and diffuses slowly in blood for the gaseous phase of the microbubbles.
In particular, the SonoVue microbubbles, thanks to the high flexibility of their shell, are strongly echogenic in a wide range of frequencies and acoustic pressure and therefore can be used with both destructive and conservative contrast bubble specific imaging methods.

See also Coherent Contrast Imaging.