On the destruction of microbubble ultrasound contrast agents

Abstract

In recent years, the use of microbubble ultrasound (US) contrast agents as carriers in drug and gene delivery applications has intensified the need for a clear understanding of the processes involved in their destruction. In this study, an analysis of the conditions in the shell of a contrast agent particle has been made, based on the full numerical solution of a modified Rayleigh–Plesset equation. The results indicate that extremely high shell stresses may be expected under typical clinical conditions. Examination of previous experimental evidence in the light of these findings suggests that the shells are almost invariably disrupted, even if they are not visibly destroyed. This has some serious implications, both for targeted delivery processes and reliable assessment of the potential for harmful bioeffects. At present, neither the model nor the experimental data provide an adequate description of contrast agent behaviour. This is due primarily to the lack of information regarding the mechanical response of the shell material and the restriction of the model to the case of small, spherically symmetrical oscillations. Methods for addressing these deficiencies in future work are proposed. (E-mail: e_stride@meng.ucl.ac.uk)