Molecular imaging has the potential for the diagnosis of disease at the earliest causative stages, development of disease biomarkers, characterization of the preclinical stages of metabolic or molecular disturbance, and real-time monitoring of disease progression as well as therapeutic response. While many methods have been proposed for molecular imaging in vivo, factors such as suboptimal spatial resolution and the use of invasive contrast agents have limited their application in clinical settings. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing, high resolution imaging technique, which is widely utilized clinically to provide exquisite anatomical images. Chemical exchange provides an opportunity to make MRI sensitive to information about the concentrations of endogenous metabolites and their environments. In this Dissertation, we developed and implemented techniques that exploit the amine proton exchange phenomenon to quantify endogenous metabolites in biological tissues, in vivo. Specifically, we developed a new method to measure proton exchange which combines chemical exchange saturation transfer (CEST) and T1rho magnetization preparation methods (CESTrho) to detect metabolites with exchangeable protons in the slow to intermediate exchange regime with enhanced sensitivity. Furthermore, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate, and thereby to pH, while retaining linear dependence on metabolite proton concentration. Additionally, for the first time, the CEST effect from amine protons of glutamate (GluCEST) was characterized and exploited to image Glu with high spatial resolution in the brain and spinal cord at ultra-high field (≥7T). Finally, we characterized the CEST effect of creatine kinase reaction metabolites and developed and optimized methods for measuring the CEST effect from Cr (CrCEST). The feasibility of measuring changes in CrCEST in calf muscles following plantar flexion exercises was shown with high spatial resolution. These methods and applications demonstrate the potential of amine CEST MRI to non-invasively and quantitatively measure endogenous glutamate and creatine changes in vivo with high resolution, which can be exploited as biomarkers of diagnosis and treatment monitoring in a range of pathologies.
Adviser: Ravinder Reddy. Thesis (Ph.D. in Bioengineering) -- University of Pennsylvania, 2013. Includes bibliographical references.