Manipulating Microbubbles: Steering Ultrasound Contrast Agents Using Acoustic Radiation Forces

Abstract

Ultrasound contrast agents are micron-sized bubbles that are used for ultrasound imaging enhancement and that can potentially be used for targeted drug delivery applications. One strategy to manipulate them inside the cardiovascular system is to use the Bjerknes force, caused by the phase difference between a transmitted ultrasound pressure wave and the microbubble volume oscillations induced by the pressure wave. Although the mechanism causing this force is well established, the balance between ultrasound-induced forces and hydrodynamic forces is poorly understood when the microbubbles are immersed in physiologically-realistic Reynolds and Womersley number flows. In this thesis, experiments were conducted in a cylindrical tube under steady and pulsatile flows over a range of Reynolds and Womersley numbers relevant to drug delivery in the systemic circulation. Two experimental setups were developed: one in which the microbubbles were imaged using a clinical ultrasound imaging system, and a second in which they were imaged by high-speed video using a long distance microscope. In the ultrasound experimental setup, a commercial L15-7io transducer was used to image microbubbles in quiescent, steady, and pulsatile flows. These experiments were extended in the optical experimental setup to explore higher Reynolds numbers. In the optical experiments, individual microbubble trajectories were captured at high magnification and high temporal resolution to determine the relationship between acoustic and hydrodynamic forces. The relative scaling of these forces was computed for different acoustic pressure amplitudes and pulse repetition frequencies. The Bjerknes force scaled linearly with pulse repetition frequency and quadratically with acoustic amplitude. The displacement of the microbubbles due to the ultrasound decreased with increasing Reynolds number suggesting a threshold for clinical applications due to the residence time of microbubbles in the ultrasound beam.