Optically observed microbubble coalescence and collapse

Understanding the mechanisms of microbubble destruction is needed for the development of ultrasound guided drug and gene delivery methods and for the improvement of diagnostic ultrasonic contrast agent (UCA) detection methods. We performed 482 experiments on the coalescence and collapse mechanisms of a soft-shelled and a hard-shelled contrast agent, by subjecting an experimental lipid-shelled UCA and the hard-shelled UCA Quantison™ to 500 kHz, high-pressured ultrasound (MI≈1.0), and recording microscopic images of these events with a fast-framing camera. Results showed that bubble fragmentation into smaller bubbles is the primary mechanism for lipid-shelled contrast microbubble destruction during the first cycles after ultrasound arrival. In 28% of our experimental events with a lipid-shelled UCA, we observed bubble coalescence. The coalescence mechanism was observed to be analog to the process described for larger gas bubbles. Repetitive coalescence and fragmentation was clearly recorded with a fast-framing camera. We also demonstrated the formation and collapse of large lipid-shelled bubbles and bubble clusters. Furthermore we showed that sonic cracking is feasible for the hard-shelled contrast agent Quantison™.