Author ORCID Identifier
Date of Graduation
Doctor of Philosophy (PhD)
James A. Bankson, Ph.D.
John D. Hazle, Ph.D.
R. Jason Stafford, Ph.D.
Aradhana M. Venkatesan, M.D.
Arvind Rao, Ph.D.
Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.
In this work, we present innovative strategies for measurement of tissue perfusion and metabolism with HP MRI. These techniques include the capacity to sensitize the imaging signal to the diffusive motion of HP molecules, providing improved accuracy and reproducibility for assessment of agent uptake in tissue. The proposed methods were evaluated in numerical simulations, implemented on a preclinical MRI system and demonstrated in vivo in rodents through imaging of HP 13C urea. Using the simulation and imaging infrastructure developed in this work, established methods for encoding HP chemical signals were compared quantitatively. Lastly, our method was adapted for imaging of [2-13C]dihydroxyacetone, a novel HP agent that probes enzymatic flux through multiple biochemical pathways in vivo.
Our results demonstrate the capacity of HP MRI to measure tissue perfusion and metabolism in ways not possible with the imaging modalities currently available in the clinic. As the use of HP MRI advances in clinical investigations of human disease, these imaging measurements can offer real-time and individualized information on disease states for early detection and therapeutic guidance.
Magnetic Resonance Imaging, Molecular Imaging, Metabolic Imaging, Hyperpolarized MRI, Pharmacokinetic Modeling, Quantitative Imaging
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biological and Chemical Physics Commons, Medical Biochemistry Commons, Medical Biophysics Commons, Medical Biotechnology Commons, Medical Molecular Biology Commons, Neoplasms Commons, Nutritional and Metabolic Diseases Commons, Radiology Commons