Ultrasound-mediated destruction of contrast microbubbles used for medical imaging and drug delivery

Micron-size bubbles encapsulated by a stabilizing layer of surface-active materials are used in medical ultrasound imaging and drug delivery. Their destruction stimulated by ultrasound in vivo plays a critical role in both applications. We investigate the destruction process of microbubbles in a commercially available contrast agent by measuring the attenuation of ultrasound through it. The measurement is performed with single-cycle bursts from an unfocused transducer (with a center frequency of 5 MHz) for varying pressure amplitudes at 50-, 100-, and 200-Hz pulse repetition frequencies (PRF) with duty cycles 0.001%, 0.002%, and 0.004%, respectively. At low excitation, the attenuation is found to increase with time. With increased excitation level, the attenuation level decreases with time, indicating destruction of microbubbles. There is a critical pressure amplitude (similar to 1.2 MPa) for all three PRFs, below which there is no significant bubble destruction. Above the critical pressure amplitudes the rate of destruction depends on excitation levels. But at high-pressure amplitudes the destruction becomes independent of excitation pressure amplitude. The results are interpreted to identify two different mechanisms of bubble destruction by its signature in attenuation, namely, slow dissolution by diffusion and catastrophic shell rupture. The different modes are discussed in detail with their implications in medical applications. (c) 2005 American Institute of Physics.