Forced nonlinear responses of lipid-coated monodisperse ultrasound contrast agents
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Ultrasound contrast agents (UCA) are coated microbubbles used to enhance the contrast-to-tissue ratio in diagnostic ultrasound images. Unlike other types of coatings, studies have shown that the shell rheological and interfacial properties of lipid-coated microbubbles vary as the lipid surface concentration changes during bubble oscillations. The goal of this dissertation was to investigate the radius-dependent shell rheological properties and their impact on the excitation parameters required to drive subharmonic oscillations and emissions from lipid-coated microbubbles. A microfluidic flow-focusing device was used to produce monodisperse lipid-coated UCA microbubbles populations, which enabled a thorough investigation of the lipid shell rheological properties. A common method for estimating the lipid shell rheological properties is to compare the frequency-dependent attenuation coefficients predicted theoretically and measured experimentally. Nonlinear attenuation equations with consideration of the non-uniform pressure field (NEWNP) were developed for the first time and coupled with a bubble dynamics equation that simulated radius-dependent shell elasticity and bubble wall surface tension during large amplitude bubble oscillations. Compared to linearized equations, the NEWNP equations generated frequency-dependent attenuation coefficient curves that more accurately reflected frequency-dependent attenuation coefficient curves determined experimentally as a function of pressure. A protocol was developed to compare attenuation curves generated via theoretical simulations and experimental measurements and estimate shell elasticity, shell viscosity, and most importantly, the initial surface tension for the first time as a function of lipid shell composition. Finally, the subharmonic acoustic emissions from the monodisperse lipid-coated UCA microbubble suspensions were studied both from theoretical prediction and experiments. It was found that the minimum pressure at which subharmonic scattering signals originated (i.e., subharmonic threshold) for the lipid-coated microbubbles with low initial surface tension approached zero over a range of frequencies regardless of the bubble size or lipid coating materials used in this study.