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