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Harnessing Cavitation for Therapy

Final Report Summary - THERACAV (Harnessing Cavitation for Therapy)

Medical applications of acoustic cavitation, such as reversible and transcranial disruption of the blood-brain barrier, for the purpose of treating Alzheimer’s, Parkinson’s and brain cancers, depend critically on the detection of acoustic emissions generated during the driven cavitation bubble activity. Signature components of these emissions are used to monitor treatments including in real-time, for assessment of drug delivery efficacy, and avoidance of overtreatment leading to permanent collateral damage, in particular. Remarkably, the mechanisms through which microbubble-cavitation generate non-linear emission, including harmonics and subharmonics, under focused ultrasound exposure are not well understood, despite many decades of fundamental cavitation research.

The TheraCav project was dedicated to developing an essential understanding of cavitation-bubble dynamics, under typical therapeutic ultrasound exposure, and reconciling that activity directly to the acoustic emissions generated. A state-of-the-art high speed imaging facility was constructed and meaningfully implemented, incorporating two high-speed cameras and synchronous pulsed laser illumination for shadowgraphic imaging of cavitation behaviour at nanosecond temporal resolutions. In parallel, intimate acoustic detection with a range of medical, commercial and in-house developed bespoke detectors, was conducted.

The results conclusively demonstrate that non-linear cavitation emissions can be mediated via periodic shock scattering from repeated bubble collapses. These findings are disruptive to the literature on the topic, to-date, and can account for all non-linear emission components, dependent on focused ultrasound driving parameters.
Throughout the history of cavitation research, there has been a pervasive tendency to classify cavitation activity – and cavitation mediated effects – as either ‘stable’ or ‘inertial’, based on the components of non-linear acoustic emissions detected. TheraCav research has generated persuasive evidence to suggest that all non-linear cavitation emissions are shock wave mediated (a conventionally inertial effect). This indicates that the enduring conventional classification is, at best, inadequate and likely unhelpful. Rather, cavitation typical of medical therapy, displays the characteristics associated with both stable and inertial categories.

The TheraCav project has overhauled fundamental understanding of cavitation activity, exposed to focused ultrasound typical of medical therapy. In particular, the research has shed new light on the acoustic signals generated by driven bubbles, for a new understanding of the interaction with detection devices. Moreover, exciting insights to potential mechanisms of therapy and unwanted bioeffect have been made, subject to in-vivo validation.