Ultrasound Microbubble Contrast Agents for Diagnostic and Therapeutic Applications: Current Status and Future Design

U l t r a s o u n d c o n t r a s t a g e n t s a r e h i g h l y e c h o g e n i cmicrobubbles with many unique properties. Microbubbles canbasically improve the sensitivity of conventional ultrasoundimaging to the microcirculation. The resonance of microbubbles in response to an incident ultrasound pulse results in nonl ine a r ha rmoni c emi s s ion tha t s e rve s a s the s igna tur e ofmicrobubbles in microbubble-specific imaging. Inertial cavitation and destruction of microbubbles can produce a strongmechanical stress enhancing the permeability of the surrounding tissues, and can further increase the extravasation of drugsfrom the blood into the cytoplasm or interstitium. Stable cavitation by high-frequency ultrasound can also mildly increasetissue permeability without causing any damage even at a highacoustic pressure. Microbubbles can carry drugs, release themupon ultrasound-mediated microbubble destruction, and simultaneously enhance vascular permeability to increase drug deposition in tissues. Various targeting ligands can be conjugated to the surface of microbubbles to attain ligand-directed andsite-specific accumulation for targeted imaging. In addition to current developments inmicrobubble technology, this review introduces our studies of the applications of microbubble-specific imaging, ultrasound-aided drug delivery, and targeted imaging. These applications are promising but may require further improvement for clinical use.