| Summary: | Modern advances in ultrasound imaging technology have led to the development of targeted microbubble contrast agents; micrometer sized encapsulated bubbles coated with binding agents. Their gas core gives them high echogenicity, scattering incident ultrasound and allowing them to oscillate to producing a detectible sound of their own. The binding agent allows them to be used for molecular imaging. The work in this thesis aims to provide a better understanding of the behaviour of microbubble contrast agents, but with a focus on their use as molecular imaging agents. The thesis starts with an introduction to microbubble contrast agents, stating their current clinical usage both as a normal contrast agent and for molecular imaging and highlighting their strengths and limitations. In the following chapter, the theory behind the modelling of microbubble motions is introduced, discussing modelling bubble oscillations using the Rayleigh-Plesset equation, and the translation of a bubble in an acoustic field through Bjerknes forces. The first piece of novel work to be presented in this thesis is in the form of a model for non-spherical oscillations in microbubble contrast agents, with the application of modelling the destruction of microbubble contrast agents. A Boussinesq-Scriven approach was taken, to adapt a pre-existing model for shell free bubbles by taking into account the viscoelastic effect of the shell. Results calculated using the developed model showed a significant difference in destruction threshold between the shelled and shell-free bubbles. The second piece of work focuses on the effects of an ultrasound field on adherent microbubbles including their detachment and deflation. Analysis of experimental results on targeted microbubbles adherent to a micro-tube with flow shows that the effects of ultrasound are significant even at relatively low acoustic pressure. As acoustic pressure is increased, the percentage of detached and/or deflated microbubbles does also. Four forces are identified which could be responsible for detachment, namely, shear, primary and secondary Bjerknes, and oscillations and their relative significance is investigated. The results from this work are then used to make suggestions about the clinical imaging for targeted contrast agents. The final novel piece of work presented is a dual transducer arrangement as a potential method of increasing targeted microbubble binding efficiency through the creation of a simple one-dimensional acoustic manipulator, capable of being implemented in any clinical ultrasound scanner with a phased array. Simulations and experimental investigations were carried out on the system in order to demonstrate the feasibility of such an acoustic manipulator and to gain understanding of its practicalities.
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