Characterization of Ultrasound Pressure Fields, Microbubbles and Their Interaction

Thesis (Ph.D.)--University of Washington, 2015Ultrasound’s therapeutic applications are increasing daily, and have spread in different medical fields, such as cardiology, sports medicine, urology, oncology, and even the field of cosmetics. Focused ultrasound (FUS) has shown the ability to target a millimeter-size spot inside the body without damaging intervening tissue, generate cavitation bubbles, or activate exogenous bubbles (e.g., ultrasound contrast agents) to enhance therapeutic effect. Although the mechanisms by which FUS creates therapeutic effects are known to be thermal and mechanical, every modality enhances different aspects of the mechanical or thermal effects. For this reason, it is essential to characterize the ultrasound pressure field of different clinical devices, as each one can provide insight of the physical mechanism for its therapeutic application. Ultrasound contrast agents (UCA’s) are encapsulated gas bodies with a thin shell that stabilizes them, ranging in size from 1-10 µm in diameter. Their initial clinical application was for medical imaging of the heart muscle. For therapeutics, microbubbles have the potential to become drug vehicles, mechanical actuators, and cavitation nuclei inside the body to induce mechanical changes. In order to use microbubbles more effectively for both imaging and therapeutic applications, in is essential to know how the material properties of their stabilizing shells can influence their dynamical behavior and how to characterize and control their size. With newer contrast agents having loaded drugs, targeted ligands and fluorescent molecules loaded on their shell, there is a need to characterize and understand how these systems respond to ultrasound. Whether the biomedical application is imaging or therapeutically related, the aim of the research in this thesis is to understand ultrasound pressure fields and its interaction with microbubbles. I have adapted specific tools to explore these areas, including high speed imaging, fiber optic probe hydrophone, laser Doppler vibrometry, finite element modeling, and flow cytometry