Non-linear cavitation cloud oscillations in High-Intensity Focused Ultrasound

Cavitation driven by high-intensity focused ultrasound is being investigated as a potential mechanism for therapeutic ultrasound. In this role, the mechanical bubble activity could be used for localised tissue disruption, facilitating targeted drug delivery. The cavitation sub-harmonic signal, which is emitted at sub-multiple values of the driving frequency, is often used to discern the onset of cavitation at a level sufficient to elicit a required bio-effect. Despite this, a convincing mechanistic source for the signal has been elusive. In this paper, we report on high-speed observations of non-linear cloud oscillatory response to propagating HIFU insonations, at two intensities typical of those used for therapeutic applications. Single cavitation clouds are reproducibly introduced to the focus of a 254 kHz HIFU field at peak-to-peak pressure amplitudes of 0.48 and 0.62 MPa, and the subsequent activity is resolved via high-speed shadowgraphic imaging at 1 × 106 frames per second. Cavitation clouds develop rapidly from nucleation, via component bubble fragmentation, and undergo repetitive oscillations from t ≈ 30 μs following nucleation, periodically emitting shock-waves at moments of concerted cloud collapse. The frequency of cloud collapse, and coincident shock-emission, occurs at one-half (~127.0 kHz) of the driving frequency at 0.48 MPa, and one-third (~84.7 kHz) of the driving at 0.62 MPa. By way of analysis, cloud oscillations are compared to a single bubble Rayleigh-Plesset model, subject to equivalent acoustic conditions. The comparison is favourable for selected values of model quiescent radius, in terms of the period of oscillation - and therefore shock-wave emission frequency - at each of the pressure amplitudes. We conclude that periodic shock emission from acoustically driven cavitation clouds provides a previously unidentified source of the sub-harmonic signal