Magnetic Resonance Imaging Techniques For Contrast - Enhanced Cellular And Molecular Imaging

Abstract

In this thesis, I aimed to demonstrate the capability and versatility of Magnetic Resonance Imaging (MRI) to perform diagnostic imaging at different physical scales, from physiological to cellular and finally at the molecular level. Chapter 2 illustrates the ability of `Dynamic Contrast Enhanced Magnetic Resonance Imaging¿ or `DCE-MRI¿ to measure an important physiological parameter that is a biomarker of nutrient delivery, which is hemodynamic perfusion. The use of a T1-reducing contrast agent in facilitating DCE-MRI in the mouse pancreas is described. A mathematical approach to quantify tracer pharmacokinetics in order to estimate blood flow is also illustrated. The competency of DCE-MRI to distinguish between normal and angiogenesis-impaired pancreas in a STAT3 knock-out mouse model is also be presented.

Chapter 3 ventured higher up the magnification scale into the cellular regime, whereby cellular tracking of exogenous cells transplanted for tissue repair was visualized with positive contrast. Superparamagnetic iron-oxide particles (SPIO) were the selected passive probes that acted as beacons of delivered cells. The superior detection sensitivity offered by a Multiple-Echo Ultrashort Echo Time (MUTE) MRI technique was demonstrated. In addition, I proposed a novel method that provides robust positive contrast with high temporal efficiency to advance cellular tracking technology. The physical principles of positive contrast sensing and factors affecting detection sensitivity are discussed.

Finally, molecular imaging is demonstrated in Chapter 4 via the use of an avant-garde technique that permits real-time dynamic monitoring of carbohydrate metabolism, this is `Dynamic Nuclear Polarized 13C Magnetic Resonance Spectroscopy (DNP-MRS)¿. Here, the biomarkers of interest were also the molecular probes themselves. They are the downstream biomolecules of pyruvate metabolism, including [1-13C] lactate, 13CO2, H13CO3- and [1-13C] acetyl-carnitine. In addition, the generation and utilization of these substrates were dependent on underlying enzyme activity such as pyruvate dehydrogenase (PDH), carbonic anhydrase (CA) and carnitine acetyltransferase (CAT). By measuring the MR signal amplitude of these reporting probes, I was able to quantify critical biological parameters such as intracellular pH, and track its changes at the onset of ischaemia. I also demonstrated the utilization of this technique to study the dynamic energy storage mechanism of the heart. The potential of [1,4-13C] fumarate as a biomarker of necrosis in the heart was also investigated. Finally, 2-dimensional mapping of metabolic activity was performed with chemical shift imaging (CSI).