Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Ivan J. Dmochowski

Abstract

Modern clinical applications require precise positional and temporal information regarding pathological changes in cells and tissues. For example, in magnetic resonance microscopy, better than 100 sq. micros per voxel spatial resolution is necessary for imaging capillary blood vessels. And in order to monitor the blood flows in brain tissues, a series of images must be acquired in less than 2 s intervals. Further, molecular imaging aims at visualizing molecules and molecular events that occur at a cellular level, i.e. sensing biological events at a fundamentally microscopic level. When compared to other imaging modalities, the main advantages of magnetic resonance imaging (MRI) are its millimeter-scale spatial resolution and wide applicability achieved with minimal perturbation to in vivo systems, whereas its major drawbacks are limited sensitivity (10 protons in a million contribute to magnetic resonance) and high cost (a million US dollars each MRI scanner). One promising solution to both problems is the combination of hyperpolarized 129Xe MRI with biosensors, which offers significant sensitivity enhancement at a much lower cost.

This dissertation reports my progress in hyperpolarized 129Xe nuclear magnetic resonance (NMR) studies for use in future molecular/medical MRI applications. First, I provide an overview of molecular imaging and, specifically, magnetic resonance imaging (MRI). 129Xe NMR/MRI is particularly promising as it solves solves the common problems of signal intensity and specificity (by employing biosensors).

In chapter 2, I present our hyperpolarization (nuclear spin polarization) method. A hyperpolarized 129Xe chemical exchange saturation transfer (Hyper-CEST) method was also applied to lower the biosensor detection limits significantly. These experiments were made possible through the development of a home-built 129Xe hyperpolarizer, continuous-flow hyperpolarized Xe delivery setup, Hyper-CEST pulse sequence, and accompanying NMR control programs.

In chapter 3, interactions between various biosensors and their target proteins have been characterized and analyzed in finer detail than previous studies. 129Xe NMR studies for biosensors targeting human carbonic anhydrase, alpha_{v}beta_{3} integrin, and pH changes have been carried out.

In chapter 4, hyperpolarized 129Xe chemical exchange saturation transfer (Hyper-CEST) NMR experiments have demonstrated unprecedented detection sensitivity for a synthetic xenon host molecule, tri-acetic acid cryptophane.

In chapter 5, to describe interactions between xenon and bacterial spores, Hyper-CEST has been successfully applied; Xe is demonstrated to be a good probe of the spore interior structure. Six spores strains with different protective layers were clearly distinguished by Xe exchanges between spore and water, observed by Hyper-CEST.

Finally, these results are summarized in chapter 6.

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