Abstract

Biomedical ultrasound is widely employed as an imaging modality for anatomical assessment and to provide information on blood flow characteristics. There is increasing interest in employing microbubble contrast agents for diagnostic and therapeutic ultrasound. Unlike MR and CT agents, ultrasound contrast agents are comparable in size to a red blood cell, providing a purely intravascular agent for clinical radiology. Microbubbles are currently clinically employed in echocardiography and liver applications, as well as pre-clinically, for the tumors' characterization and quantifying perfusion. Critical to the effectiveness of contrast agent microbubbles is an understanding of their nonlinear vibrations and scattering within the vasculature, specifically within the microvasculature where standard ultrasound flow estimation suffers from slow blood velocity and low red blood cell concentration.
Using mainly a finite element computational approach, this thesis aims to investigate the nonlinear physics of ultrasound-stimulated microbubbles within small capillaries to shed some light on the vibration dynamic and behavior of microbubble contrast agents. Over three chapters of results, this thesis analyses the complex vibration dynamics of microbubbles in proximity to each other and confined in a viscoelastic vessel. The results provided in this thesis explain how the resonance behavior of a microbubble is dampened and shifted by its neighboring bubbles and how smaller bubbles show off-resonance activities corresponding to the resonance behavior of the bigger, neighboring bubbles. The results also explain how initial phospholipid packing and bubble
proximity affect subharmonic response and how a viscoelastic vessel dampens resonance behavior and amplifies off-resonance behavior.
This thesis conducts a robust study on ultrasound-stimulated microbubble-compliant vessel interactions. It will contribute to optimal contrast agent design for both imaging and therapy, image quantification, and the development of new ultrasound pulse sequences.