| The purpose of this research was to investigate the Bioeffects resulting from the exposure of blood vessels to ultrasound, and whether these Bioeffects can be used to promote vascular occlusion for therapeutic purposes. At high intensities, ultrasound has known Bioeffects that are produced via tissue heating and/or cavitation. Most Bioeffects from ultrasound are a result of two physical phenomena: absorption of acoustic energy and cavitation of gas-filled bubbles. The objectives of this dissertation were to characterize both thermal and cavitation-associated ultrasound-mediated Bioeffects to blood vessels, examine the relationship between cavitation and vascular Bioeffects, and determine whether ultrasound-mediated Bioeffects can be used to occlude blood vessels for therapeutic applications such as ultrasound-mediated sclerotherapy of blood vessels.; The ability of high-intensity focused ultrasound (HIFU) to arrest active bleeding in lacerated blood vessels acutely and the long term sequelae of thermal coagulation were examined. HIFU was demonstrated to be effective in arresting bleeding and occluding vessels; however, significant thermal injury to perivascular tissue resulted.; To evaluate the Bioeffects resulting from cavitation, microbubble contrast agent was administered to anesthetized rabbits intravenously followed by exposure of vessels to 1-MHz ultrasound of varying pressure amplitudes and sub-thermal temporal average intensities. Damage to the endothelial surface showed a correlation with the applied peak negative acoustic pressure (P-), with a pressure threshold for endothelial cell damage identified to be between 3.35--6.5 MPa. Furthermore, histology showed no sign of thermal damage to perivascular tissues. Additional studies demonstrated a clear correlation between detected inertial cavitation activity and the percent of endothelial surface area damaged.; Studies were performed to determine if vascular occlusion could be achieved by exposing vessels in vivo to ultrasound parameters known to result in cavitation-associated endothelial surface damage. Vessels were exposed to low duty factor ultrasound (1.17 MHz driving frequency, 9 MPa P -, 5000 cycle pulse, and a 1 Hz pulse repetition frequency) in the presence of circulating ultrasound contrast agent. Ultrasound exposure alone resulted in a non-occlusive intravascular thrombus; however, with local injection of fibrinogen, an occlusive thrombus formed at the site of US exposure. These results have potential clinical applications for hemostasis and sclerotherapy. |
