The first generation ultrasound contrast agents (UCA/USCA) do not pass the pulmonary vascular bed, and are therefore limited to the venous system and the right heart cavities after intravenous injection.

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.

Albunex and Infoson, used mainly in cardiac evaluations, are first generation one-pass-only contrast agents and have been replaced by the new-generation contrast media. Albunex and Infoson are the same sonicated human serum albumin microbubbles. Infoson is licensed and manufactured in Europe, while Albunex was produced in the USA.
Albunex, an air-filled microbubble with a denatured albumin shell (modified from air-filled albumin microspheres prepared from sonicated 5% human serum albumin), was the first FDA-approved contrast agent, but is no longer in production.
Cardiac shunts and valve regurgitations are often evaluated with Color Doppler Imaging (CDI), which also improved with injections of Albunex, but this agent is pressure-sensitive and does not recirculate. It is effectively a one-pass-only agent, limiting its clinical efficacy.

See also First generation USCA, Echocardiography and Contrast Enhanced Ultrasound.

From Bayer Schering Pharma AG:
Available in Europe since 1996 and in Japan since 1999. Currently, the marketing situation is unclear.
Levovist® is a first generation USCA consisting of galactose (milk sugar) ground into tiny crystals whose irregular surfaces act as nidation sites on which air pockets form when it is suspended in water, much as soda water bubbles form at small irregularities on the surface of the glass. A trace of palmitic acid is added as a surfactant to stabilize the resultant microbubbles. When Levovist® dissolves in blood, air trapped inside the galactose is released as free gas bubbles. These bubbles have a weak encapsulating shell and are easily destroyed by ultrasound.
Different contrast ultrasonography methods have been developed since the introduction of Levovist®. Initially, Levovist® was an echo contrast medium for improving sensitivity in color Doppler and Power Doppler examinations, but was found to suffer from significant blooming, making it difficult to observe small blood vessels. However, Levovist® improves the accuracy of echocardiographic examinations in such indications as assessment of left ventricular function.
In addition to their vascular phase, some ultrasound contrast agents (USCAs) can exhibit a tissue- or organ-specific phase. Levovist® can accumulate within the liver and the spleen for up to 20 min once it has disappeared from the blood pool and improves the detectability of focal liver lesions and allows more reliable control of interventional tumor treatments. Varied types of information can be obtained by applying contrast imaging at different times after the injection using Levovist® in both the arterial phase and the late organ-specific phase.
1 g Levovist® granules contain 999 mg D-galactose and 1 mg palmitic acid.
Brand names in other countries: Levovist/Levograf

Sonazoid™ is an ultrasound contrast agent (UCA) consisting of stabilized gas microbubbles in an aqueous suspension. Sonazoid™ has overcome the stability problems of first generation USCA and can produce myocardial perfusion images. Myocardial imaging using ultrasound contrast agents provides diagnosis of chronic heart disease and assessment of the coronary arteries and of the coronary blood flow reserve.
Sonazoid™ is taken up by healthy Kupffer cells in the liver and spleen, but break down in high amplitude ultrasound imaging modes such as color Doppler imaging. The bubble rupture produces a transient pressure wave, which results in a characteristic mosaic color pattern from tissues containing the microbubbles (induced acoustic emission). Liver tumors without Kupffer cells will not display the mosaic pattern and can therefore be identified easily.