Spatial Control of Cavitation in Therapeutic Ultrasound

Inertial cavitation has been implicated as the primary mechanism for a host of emerging applications. In all these applications, the main concern is to induce cavitation in perfectly controlled locations in the field; this means specifically to be able to achieve cavitation threshold at the geometrical focus of the transducer without stimulating its near field. In this study, we make use of dual-frequency methods to preferentially lower the cavitation threshold at the focus relative to the rest of the field. One family of dualfrequency driving waveforms is evaluated in a bubble model incorporating rectified diffusion. Theoretical predictions based on Sokka's work (Sokka 2003a) are confirmed in vitro using OptisonT, a commercially available contrast agent. The performance of the rest of acoustic field in suppressing cavitation when cavitation is induced at the focus is investigated theoretically and checked experimentally. This first part shows that dualfrequency phased arrays could be used to precisely control cavitation. Cavitation threshold is proved to be 1.2 times higher in the near field than at the focus. One of the main limitations of the aforementioned protocol is that it is tightly controlled. As an example, Optisonm has a mean bubble size of 2 4.5 pm, which means that the initial bubble radii will fall in this range. Since cavitation threshold has been proved to depend on this parameter, using ultrasound contrast agents allows for more predictable results. Therefore, in the second half of this study, we propose a focused ultrasound protocol that induces and monitors gas bubbles at the focus and allows for ex vivo validation of the aforementioned theoretical results. The experiments involve fresh rabbit tissue and a statistical analysis is performed over data collected from back muscle. Moreover, the experimental apparatus is designed to be MRI-compatible to make future in vivo assessments feasible. This second half of the study demonstrates that the theoretical predictions made earlier can reliably be used to predict dual-frequency cavitation thresholds. It also suggests that clinical use of dual-frequency excitations might be a solution to the problem of spatial control of cavitation. Thesis Advisor: Kullervo Hynynen, PhD Title: Professor of Radiology, Harvard Medical School and Brigham and Women's Hospital