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Engineering Ultrasound Contrast Agents for Increased Stability and Nonlinearity

Azmin, M; (2016) Engineering Ultrasound Contrast Agents for Increased Stability and Nonlinearity. Doctoral thesis , UCL (University College London). Green open access

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Abstract

There has been increasing interest in the use of microbubbles as contrast agents in various diagnostic and therapeutic applications of biomedical ultrasound. New techniques have been developed which rely upon nonlinear scattering of acoustic waves by contrast agents undergoing volumetric oscillations upon exposure to ultrasound. The degree of nonlinearity can be improved by increasing the amplitude of the insonation pressure. This may, however, increase the risk of destroying the contrast agent and produce undesirable side effects either through inducing shear stress around them, or by undergoing inertial cavitation. The latter phenomenon is associated with high temperature and extreme pressures and can potentially damage the tissue surrounding the bubble. A further problem is the change in contrast agent size due to dissolution which is an important factor in determining their response to ultrasound. A proposed solution to these issues is to deposit solid nanoparticles on the outer surface of the microbubbles to form a semi-solid shell upon reaching a certain surface density. As the bubbles undergo volumetric oscillations, the particles offer resistance when bubbles contract but not during expansion. The asymmetry of oscillations is thus increased and the nonlinear character of the acoustic response is improved. In addition, the particles stabilize the microbubbles by inhibiting the transfer of gas to surrounding liquid as well as resisting the capillary pressure due to interfacial tension. This thesis commences with a review of the current literature followed by a review of theoretical models for the dynamics and dissolution of free and coated microbubbles. A new dissolution model accounting for the effect of nanoparticles and a surfactant coating is then proposed and simulations compared with experimental results obtained from collaborators. A current dynamic model describing a coated microbubble is evaluated. This is then expanded to provide a new dynamic model for a contrast agent with a finite thickness shell with variable surface tension and viscosity. Finally the microfluidic method for producing contrast agents is studied through a computational fluid dynamic model followed by recommendations for future directions of study.

Type: Thesis (Doctoral)
Title: Engineering Ultrasound Contrast Agents for Increased Stability and Nonlinearity
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: Ultrasound contrast agents
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1508365
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