The persistence of microbubbles is depended of the shell stability and the density of the gas.
This is defined by the equation:
(R x d)/(DIFS x const_sat)
where R is the bubble radius, d the gas density, DIFS the gas diffusivity and const_sat the saturation constant.
Microbubbles are stabilized with thin coatings of substances such as palmitic acid or by encapsulation in microspheres made with albumin, lipids, or polymers. Low-solubility low-diffusibility gases dramatically improve the persistence. Most recently developed ultrasound contrast agents combine these two approaches to prolong contrast enhancement.
Persistence is also a type of temporal smoothing used in both gray scale and color Doppler imaging. Successive frames are averaged as they are displayed to reduce the variations in the image between frames, hence lowering the temporal resolution of the image.

EchoGen® is a fluorocarbon-based (dodecafluoropentane) third generation USCA. EchoGen® consists of microbubbles stabilized with surfactants in a phase shift colloid emulsion (perflenapent). EchoGen® requires no preparation, reconstitution, or refrigeration.
Perflenapent emulsion would represent a significant advance in contrast echocardiography caused by effective and long lasting opacification of the left ventricle and enhanced endocardial border delineation.
The persistence of the contrast effect permits interrogation in multiple echocardiographic views, as well as the visualization and localization of myocardial perfusion deficits at rest by producing a negative contrast effect.
October 12, 2000
Sonus Pharmaceuticals, Inc. announced a strategic decision to refocus the Company on the development of its drug delivery and blood substitute products. At the same time, Sonus has withdrawn the NDA (New Drug Application) and discontinued clinical activity for its ultrasound contrast product, EchoGen®.
August 06, 2001
Sonus Pharmaceuticals, Inc. announced that it has entered into an agreement to sell its ultrasound contrast assets for $6.5 million to Amersham plc. As part of the agreement, Sonus has also assigned to Nycomed its interest in the ultrasound contrast patent license agreement entered into with Chugai Pharmaceutical Co. Ltd. and Molecular Biosystems Inc in January 2001.

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.

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.

(UCA / USCA) Ultrasonography is the most commonly performed diagnostic imaging procedure. The introduction of sonographic contrast media into routine practice modifies the use of ultrasound in a variety of clinical applications. USCAs consist of microbubbles filled with air or gases and can be classified according to their pharmacokinetics. Among the blood pool agents, transpulmonary ultrasound contrast agents offer higher diagnostic potential compared to agents that cannot pass the pulmonary capillary bed after a peripheral intravenous injection. In addition to their vascular phase, some USCAs can exhibit a tissue- or organ-specific phase.
The sonogram image quality is improved either by decreasing the reflectivity of the undesired interfaces or by increasing the backscattered echoes from the desired regions.

Different types of ultrasound contrast agents:
Ultrasound contrast agents act as echo-enhancers, because of the high different acoustic impedance at the interface between gas and blood. The enhanced echo intensity is proportional to the change in acoustical impedance as the sound beam crosses from the blood to the gas in the bubbles.

The ideal qualities of an ultrasound contrast agent:
A typical ultrasound contrast agent consists of a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. The choice of the microbubble shell and gas has an important influence on the properties of the agent.
Current generations of microbubbles have a diameter from 1 μm to 5 μm. The success of these agents is mostly dependent on the small size and on the stability of their shell, which allows passage of the microbubbles through the pulmonary circulation. Microbubbles must be made smaller than the diameter of capillaries or they would embolize and be ineffective and perhaps even dangerous.
The reflectivity of these microbubbles is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the contrast agent particles themselves.
Ultrasound contrast agents produce unique acoustic signatures that allow to separate their signal from tissue echoes and to depict whether they are moving or stationary. This enables the detection of capillary flow and of targeted microbubbles that are retained in tissues such as normal liver.
The new generation of contrast media is characterized by prolonged persistence in the vascular bed which provides consistent enhancement of the arterial Doppler signal. Contrast agents make it also possible to perform dynamic and perfusion studies. Targeted contrast imaging agents are for example taken up by the phagocytic cell systems and thus have liver/spleen specific effects.

See also Ultrasound Contrast Agent Safety, Adverse Reaction, Tissue-Specific Ultrasound Contrast Agent, and Bubble Specific Imaging.