Cavitation in Dual-Frequency Focussed Ultrasound Surgery for Enhanced Drug Delivery

Cavitation has clear potential to revolutionise therapeutic applications of ultrasound. Before this potential can be realised, cavitation in focussed ultrasound must be fully understood, and desirable effects identified and optimised. This is non-trivial as cavitation is a notoriously difficult phenomenon to study. The applicant and host researchers are world leaders [1,2] in the implementation of ultra high-speed cameras to study cavitation, necessary to resolve the rapid dynamics under ultrasound drivin g frequencies. This includes the recent joint development of a novel laser-based technique for controlled nucleation [3]. The proposed project will investigate cavitation-related effects at a critical temporal resolution, as yet unexplored in the literatu re; that of the sub-millisecond regime. This is the timescale over which drug release under ultrasound exposure will occur, driven by cavitation mediated distribution across tissue and cell membranes. We will integrate a colour high-speed camera and novel dual-frequency capabilities to existing custom-built apparatus, to observe fluorescence from drug-mimicking markers. This will allow the optimisation of delivery in terms of the component ultrasound exposure parameters and various encapsulation formulati ons. Parallel acoustical measurements will allow direct correlation of fluorescence release and migration with specific cavitation events and regimes.