Date of Award

Spring 1-1-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Advisor

Todd Murray

Second Advisor

Mark Borden

Third Advisor

Yifu Ding

Fourth Advisor

Jianliang Xiao

Fifth Advisor

Rafael Piestun

Abstract

Contrast agents are used across a variety of medical imaging modalities for improved visualization of structures in the body. Microbubbles, for example, efficiently scatter ultrasound thereby providing enhanced ultrasonic imaging of the vasculature. Plasmonic nanoparticles, on the other hand, are efficient optical absorbers and can provide improvements in optical and photoacoustic imaging.

The focus of this thesis is on the development of novel contrast agents capable of enhancing both ultrasound and photoacoustic imaging modalities. The first agent is constructed by templating nanoparticles onto a lipid-encapsulated microbubble with a perfluorocarbon gas core. Using an avidin-biotin conjugation scheme, control over the nanoparticle surface density is achieved. The nanoparticle shell absorbs pulsed laser radiation and heats the microbubble gas core, producing a strong photoacoustic response. Upon destruction of the microbubble gas core the photoacoustic response is diminished. A model of laser driven bubble oscillations is presented and the amplitude and frequency correlate well with experiment. Contrast enhanced dual mode imaging is demonstrated in a tissue phantom and contrast is quantified. In addition, the properties of individual nanoparticle-coated microbubbles, such as the shell elasticity and viscosity, are found by exciting them with a pulsed laser source in an optical microscope and detecting the resulting oscillations using light scattering. The all optical interface is an attractive platform for the study of microbubble physics.

The second contrast agent is a nanoparticle-templated, sub-micron droplet with a liquid perfluorocarbon core. Advantages of this agent are increased circulation time and the ability to leave leaky tumor vasculature due to the sub-micron size. Nanoparticle-templated droplets are fabricated using a condensation technique, where application of high pressure to the nanoparticle-templated microbubbles causes the gas core to condense into a metastable, superheated liquid. Pulsed laser heating of the liquid core transforms the droplet back into a microbubble. The droplet undergoes explosive vaporization producing an exceptionally strong photoacoustic response. The resulting microbubble is templated with nanoparticles and capable of providing photoacoustic and ultrasound contrast. The core material of the droplet is found to have a strong effect on the threshold fluence for vaporization, with lower boiling temperature droplets vaporizing at a lower fluence.

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