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 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.

(CEUS) Contrast agents increase the reflection of ultrasonic energy, improve the signal to noise ratio and caused by that the detection of abnormal microvascular and macrovascular disorders. Contrast enhanced ultrasound is used in abdominal ultrasound (liver sonography) as well as in cerebrovascular examinations e.g., for an accurate grading of carotid stenosis. The used contrast agents are safe and well tolerated.

The quality of the enhancement depends on:
The additional use of ultrasound contrast agents (USCAs) may overcome typical limitations like poor contrast of B-mode imaging or limited sensitivity of Doppler techniques. The development of new ultrasound applications (e.g., blood flow imaging, perfusion quantification) depends also from the development of pulse sequences for bubble specific imaging. In addition, contrast enhanced ultrasound improves the monitoring of ultrasound guided interventions like RF thermal ablation.

See also Contrast Enhanced Doppler Imaging, Contrast Harmonic Imaging, Contrast Imaging Techniques and Contrast Pulse Sequencing.

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From POINT Biomedical Corp
BiSphere™ is a technology for drug delivery applications by ultrasound. BiSpheres™ consists of microparticles comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microbubbles contains a filling gas, liquid, or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The contrast agent particles are capable of passing through the capillary systems of a subject. The drug-loaded biSpheres™ would be administered intravenously and freely circulate throughout the body, while the drug encapsulated within would remain biologically unavailable. The drug would only be released when the biSpheres become flooded when passing through an externally directed ultrasound field.
The use of biSpheres™ to transport agents to specific sites within the body is expected to substantially increase local efficacy while decreasing systemic side effects or adverse reactions. The biSpheres™ may also serve to protect labile agents from metabolism or degradation. The noninvasive release of a protected, encapsulated agent can be controlled by ultrasound imaging to a depth of 20-30 cm from the skin surface.
The flexibility in size control in the biSphere™ technology has enabled the construction of submicron ultrasound contrast agents suitable for lymphatic imaging, with a diameter in the submicron range. This agent, while much smaller in size than CardioSphere®, is based on the BiSphere configuration: a shell within a shell enclosing a gas. The inner layer, made from a biodegradable polymer, provides the physical structure and controls the acoustic response. The outer layer functions as the biological interface. Each of these layers has been independently tailored to fulfill the specific requirements for lymphatic imaging.