Fast volumetric treatment using multi-focus insonation and thermal amplification

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 DESCRIPTION (provided by applicant): Magnetic resonance imaging-guided focused ultrasound (MRgFUS) has shown promise as an alternative to invasive surgery for a growing number of clinical applications, including treatment of uterine fibroids, palliation of pain from bone metastases, and treatment of neurological disorders. Although the procedure is superior to traditional invasive surgery, the duration of this treatment incurs significant cost and discomfort for patients, reducing practical implementation and impact in many cases. In this application, we propose a dual approach using multi-focus insonation in conjunction with phase change nanodroplets to dramatically improve treatment times. Multi-focus insonation is the process of using an array transducer to create a focal pattern with multiple high intensity locations that can heat tissue more efficiently than is possible with a single focus. We seek to combine this insonation method with nanodroplets that selectively amplify the thermal effects of ultrasound when activated. These particles are in a liquid state when injected but undergo phase change to microbubbles when subjected to a high-pressure acoustic pulse. Therefore, only nanodroplets in the tissue surrounding the multiple foci will undergo phase change, resulting in substantial thermal and mechanical energy amplification at this large multi-focus volume. At the same time, nanodroplets outside of the focal zone will not experience their acoustic activation threshold and will remain in the acoustically dormant liquid state, thereby avoiding thermal amplification in tissues outside of the acoustic focus, sparing healthy tissue. We hypothesize that the combination of multi-focus ultrasound and phase change nanodroplets will enable the use of MRgFUS to treat a clinically relevant volume three times faster than currently available methods while maintaining precise control over the margins of the treated region. Such an improvement would significantly reduce the time required for current clinical applications of MRgFUS and expand its role into applications where treatment of large volumes is desired but not feasible.