Butler, Mairéad Bernadette

2018-03-29T12:14:55Z

2018-03-29T12:14:55Z

2006

Microbubble agents are used to enhance image-contrast and therapy using ultrasound. Current developments of these agents include the targeting of microbubbles to attach to specific markers expressed on certain diseased cells. Inflamed areas of atherosclerosis associated with unstable plaque in arteries have been shown to express specific inter-cell adhesion molecules such as ICAM-1. In order to distinguish between areas of stable and unstable plaque an ultrasonic contrast agent has been developed in-house for imaging with high frequency intravascular ultrasound (IVUS). The contrast agent has been imaged with IVUS at 40 MHz at different stages during development.

To assess in vivo applicability of the in-house agent it was necessary to image it attached to surfaces and under flow conditions. To image microbubbles at surfaces, work was undertaken on contrast agents at agar-based boundaries. Contrast agent was attached to agarbased material using the avidin and biotin interaction. The attached microbubbles were imaged with high frequency ultrasound, from 7-40 MHz. A flow chamber was developed for use with IVUS. The attached microbubbles were imaged under flow conditions. The microbubbles were found to remain echogenic and attached to the agar at a range of flow rates from 75 - 480 ml min"1 through a flow area of 9 mm2. The peak negative acoustic pressures for a selection of high frequency transducers were determined in order to define the ultrasound imaging field.

Laser Doppler anemometry (LDA), a non-invasive high resolution technique for measuring flow velocities in liquids and gases was used to determine the flow profile within the flow chamber at the surface of the agar sample. The shear stress on the agar was calculated from the profile. Attached contrast agent was found to remain attached to agar under wall shear stresses of up to 3.4 Pa compared to a mean in-vivo arterial wall shear stress of 1.5 Pa. Free flowing in-house agent was shown to attach to prepared agar under low flow rates.

In this thesis the in-house contrast agent has been shown: to be echogenic at high frequencies, to be echogenic when attached to agar, to remain attached under physiological wall shear stresses and to attach to avidin coated agar when subjected to flow. An LDA system has been designed which can be used to assess the binding of agents as they are developed.

http://hdl.handle.net/1842/29022

The University of Edinburgh

Annexe Thesis Digitisation Project 2018 Block 17

Already catalogued

High frequency ultrasonic imaging of targeted microbubble contrast agents under controlled shear stress

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy