Ultrasound Contrast Agents

Ultrasound contrast agents are gas-filled microbubbles that are administered intravenously to the systemic circulation. Microbubbles have a high degree of echogenicity, which produces a unique sonogram with increased contrast. Microbubbles can be used in a wide variety of animal models, and are compatible with virtually all ultrasound scanners and Doppler ultrasound.

Non-Targeted Vascular Contrast Agents

Untargeted vascular contrast agents   enhance the bloodstream’s echo allowing to distinguish  blood from surrounding tissues. Untargeted CEUS  can be used (1) to evaluate blood perfusion in an organ or area of interest and (2) to evaluate the blood volume in an organ or area of interest. When used in conjunction with Doppler  Ultrasound, microbubbles can measure myocardial flow rate to diagnose valve problems. (3) Microbubbles can enhance the contrast at the interface between the tissue and blood. Rendering a clearer image of this interface gives a better picture of the structure of an organ.  

Targeted Contrast Agents

Targeted contrast agents  have targeting ligands conjugated to their surface. Targets bind to receptors or biomarkers characteristic of intravascular diseases enabling the microbubble complex to accumulate selectively in areas of interest, such as  diseased or abnormal tissues. This form of molecular imaging, known as targeted contrast-enhanced ultrasound, will only generate a strong ultrasound signal if targeted microbubbles bind in the area of interest.

Applications: 

• Inflammation : in inflammatory diseases such as  Crohn’s disease,  atherosclerosis , and even  heart attacks, the inflamed blood vessels specifically express certain receptors like αv b3 integrin ,  VCAM-1, ICAM-1, E-selectin. If microbubbles are targeted with ligands that bind these molecules, they can be used in contrast echocardiography to detect the onset of inflammation. Early detection allows the design of better treatments. 
•   Cancer: cancer cells also express a specific set of receptors, mainly receptors that encourage angiogenesis , or the growth of new blood vessels. If microbubbles are targeted with ligands that bind receptors like αv b3 integrin, they can non-invasively and specifically identify areas of cancers.
• Gene Delivery: Vector DNA can be conjugated to the microbubbles. Microbubbles can be targeted with ligands that bind to receptors expressed by the cell type of interest. When the targeted microbubble accumulates at the cell surface with its DNA payload, ultrasound can be used to burst the microbubble. The force associated with the bursting may temporarily permeablize surrounding tissues and allow the DNA to more easily enter the cells. 
• Drug Delivery: drugs can be incorporated into the microbubble’s lipid shell. The microbubble’s large size relative to other drug delivery vehicles like liposomes  may allow a greater amount of drug to be delivered per vehicle. By targeted the drug-loaded microbubble with ligands that bind to a specific cell type, microbubble will not only deliver the drug specifically, but can also provide verification that the drug is delivered if the area is imaged using ultrasound. 

Labeling Contrast Agents

Biotinylated microbubbles are an easy to use platform allowing the researcher to conjugate any biomarker or targeting ligand.