(AALs) Acoustically active lipospheres and ultrasound are under development to deliver bioactive molecules to the vascular endothelium. The AALs are similar to both ultrasound contrast agents and drug-delivering liposomes. They can carry bioactive substances using biologically inert shells and deliver those substances when disrupted by ultrasound.
The lipospheres consist of a small gas microbubble surrounded by a thick oil shell and are enclosed by an outermost lipid layer. The gas bubble contained in these vehicles makes them acoustically active, similar to ultrasound contrast agents. Acoustically active lipospheres can be nondestructively deflected using ultrasound radiation force, and fragmented with high intensity ultrasound pulses. Their lipid-oil complex can carry bioactive substances at high concentrations. An optimized sequence of ultrasound pulses can deflect the AALs toward a vessel wall then disrupt them, painting their contents across the vascular endothelium.

See also Filling Gas, and MRX 115.

Targeted ultrasound contrast agents provide advantages compared with usual microbubble blood pool agents. The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. Tissue-specific ultrasound contrast agents improve the image contrast resolution through differential uptake. Targeted drug delivery via contrast microbubbles is another contrast media concept and provides the potential for earlier detection and characterization of disease.
Targeted contrast imaging provides a higher sensitivity and specificity than obtained with a nontargeted contrast agent.
The detection of disease-indicative molecular signatures may allow early assessment of pathology on a molecular level.
Molecular imaging should be an efficient and less invasive technique to obtain three-dimensional localization of pathology.
Ultrasound agents typically remain within the vascular space, and therefore possible targets include molecular markers on thrombus, endothelial cells, and leukocytes. Targeted contrast agents permit noninvasive detection of thrombus, cancer, inflammation, or other sites where specific integrins or other adhesion molecules are expressed. Adhesion molecules such as monoclonal antibodies, peptides, asialoglycoproteins, or polysaccharides are incorporated into the shell of the microbubble or liposome. After injection into the bloodstream, the targeted agent accumulates via adhesion receptors at the affected site, enhancing detection with an ultrasound system.

See also Acoustically Active Lipospheres, and Tissue-Specific Ultrasound Contrast Agent.

The traveling ultrasonic wave causes a low-level ultrasound radiation force when this energy is absorbed in tissues (absorbed dose). This force produces a pressure in the direction of the beam and away from the transducer. It should not be confused with the oscillatory pressure of the ultrasound wave itself. The pressure that results and the pressure gradient across the beam are very low, even for intensities at the higher end of the range of diagnostic ultrasound. Mechanical effects like radiation forces lead to stress at tissue interfaces. The effect of the force is manifest in volumes of fluid where streaming can occur with motion within the fluid. The fluid velocities which result are low and are unlikely to cause damage.
The effects of ultrasound radiation force (also called Bjerknes Forces) were first reported in 1906 by C. A. and V. F. K. Bjerknes, when they observed the attraction and repulsion of air bubbles in a sound field.
While incompressible objects do experience radiation forces, compressible objects driven at their resonant frequency experience far larger forces and can be observably displaced by low-amplitude ultrasound waves. A microbubble driven near its resonance frequency experiences a large net radiation force in the direction of ultrasound wave propagation. Ultrasound pulses of many cycles can deflect resonant microbubbles over distances on the order of millimeters.
In addition to primary radiation force, which acts in the direction of acoustic wave propagation, a secondary radiation force for which each individual bubble is a source and receptor causes the microspheres to attract or repel each other. The result of this secondary force is that a much larger concentration of microbubbles collects along a vessel wall than might otherwise occur.

See also Acoustically Active Lipospheres.

Vascular ultrasound contrast agents are gas microbubbles with a diameter less than 10 μm (2 to 5 μm on average for most of the newer agents) to pass through the lung capillaries and enter into the systemic circulation. Air bubbles in that size persist in solution for only a short time; too short for systemic vascular use in medical ultrasound imaging. So the gas bubbles have to be stabilized to persist long enough and survive pressure changes in the heart.
Most vascular contrast media are stabilized against dissolution and coalescence by the presence of additional materials at the gas-liquid interface. In some cases, this material is an elastic solid shell that enhances stability by supporting a strain to counter the effect of surface tension. In other cases, the material is a surfactant, or a combination of two or more surfactants.
Typically the effective duration of vascular enhancement is a few minutes, after which the microbubbles dissipate. This rather short duration of vascular enhancement makes it easy to perform repeated dynamic studies. Intravenous vascular contrast agents will be used in imaging malignant tumors in the liver, kidney, ovary, pancreas, prostate, and breast. Tumor neovascularization can be a marker for angiogenesis, and Doppler signals from small tumor vessels may be detectable after contrast injection. Contrast agents are useful for evaluating vessels in a variety of organs, including those involved in renal, hepatic, and pancreatic transplants. If an area of ischemia or a stenosis is detected after contrast administration, the use of other more expensive imaging modalities, including CT and MRI, can often be avoided.

See also Acoustically Active Lipospheres.