Recent advances in therapeutic ultrasound have seen microbubbles – conventionally used as contrast agents for ultrasound imaging – being used for therapeutic procedures. Oscillatory actions of microbubbles, driven by ultrasound, could locally induce therapeutic effects varying from mild stimulation to destructive ablation. However, the difficulty of controlling the level of microbubble activities inside a patient remains a key obstacle to clinical translation of many procedures. One way to control the bubbles is to monitor the sound they emit, infer the level of their activities, and adjust the intensity of the excitation pulses accordingly. However, there is a lack of understanding on what the captured signals mean in terms of the bubble activities and biological responses being induced. Thus, control of the excitation pulse and, by consequence, of the types and extent of induced biological responses, remains a key challenge to clinical translation.

Studies in this thesis aim to further the understanding of the formation of captured microbubble signals. A summary of the current state of the field is given in the first chapter. The second chapter concerns the electroacoustic properties and distortion of sensors commonly used in microbubble-mediated procedures. The third chapter concerns interference of acoustic emissions from different microbubbles and how, depending on the location of the sensor relative to the bubbles, they could lead to captured signals with significantly different spectral contents. The fourth chapter builds on the said framework and explores the relationship between sensor location and microbubble concentrations. The fifth chapter concerns a more specific difficulty in processing microbubble emissions captured when using short-pulse ultrasound to deliver drugs across the blood-brain barrier. It proposes a sequence combining amplitude modulation and short pulses as a solution. Lastly, the final chapter states the remaining challenges and suggests possible future directions for microbubble emissions studies.