(639b) Engineering Microbubbles for Focused Ultrasound Therapy

Microbubbles may enhance the safety and efficacy of focused ultrasound (FUS) therapy. Microbubble oscillation in the micro-vessels and capillaries of the target tissue may lead to mechanical disruption of the endothelium, allowing macromolecular drugs to enter the interstitial regions of tissue. For example, this method can be used to transiently, noninvasively and locally open the blood brain barrier (BBB) to treat neurological diseases [1]. Likewise, this technique can be used to transfect tumors with nucleic acids, such as plasmid DNA or short interfering RNA [2]. However, the exact cause (e.g., shear stress caused by streaming, contact stress from bubble growth, water jetting from inertial cavitation etc.) of vascular permeabilization is still not known, mainly because the size polydispersity of microbubbles in previous work has precluded deduction of the underlying physical mechanism. Here, we describe methods to size select microbubbles with narrow size distribution. Stability of the size-selected microbubbles is studied. The in vivo circulation persistence and acoustic response of size- selected microbubbles during high frequency imaging is also assessed. Our results illustrate a methodology for engineering the microbubble suspension, which may lead to insights into methods to improve focused ultrasound therapy.

[1] Choi JJ, Feshitan JA, Baseri B, Wang S, Tung Y-S, Borden MA, Konofagou EE. (2010) ?Microbubble-size dependence on focused ultrasound-induced blood-brain barrier opening in mice.? IEEE Transactions on Biomedical Engineering, 57:145-54.

[2] Sirsi S, Borden MA. (2009) ?Microbubble compositions, properties and biomedical applications.? Bubble Science, Engineering and Technology, 1:3-17.