Attachment mechanisms of a novel, targeted, lipid-based, ultrasound contrast agent
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This thesis presents the development of a novel, targeted, lipid-based, microbubble ultrasound contrast agent (UCA) for assessment of coronary heart disease (CHD) with high frequency intravascular ultrasound (IVUS). The targeting mechanisms assessed for microbubble attachment include a streptavidin-biotin mechanism, electrostatic mechanism and antibody targeting. The microbubble has been optimized for use with 40MHz IVUS through an investigation into the effect of various production methods on the echogenicity of the agent. Echogenicity has been assessed from quantification of the RF data and determination of the mean ultrasound backscatter. Agitation was found to be the optimal method of production resulting in a 3.94(±1.14)dB increase in the mean backscatter. The stability of the agent has also been assessed over time and optimal storage of the agent determined. A novel flow chamber has been developed for assessment of microbubble detachment under very high WSS. The flow chamber has been calibrated to 50Pa wall shear stress (WSS) using laser Doppler anemometry (LDA). Higher WSS was achieved through the use of higher viscosity fluids. The streptavidin-biotin bond has been assessed within the flow chamber and was found to be 75 times stronger than an electrostatic control. Antibody attachment to the microbubbles via a streptavidin-biotin bridge has been optimised with 91.20(±0.02)% of the microbubbles having antibodies attached. A flow system has also been developed for assessment of microbubble attachment to cells under very low WSS. Microbubbles have been successfully targeted to SK-Hep-1 cells using acoustic radiation force. In addition attachment of the microbubbles to SK-Hep-1 cells has been observed under 0.03Pa WSS in the Ibidi μ-slides.