Off-campus WSU users: To download campus access dissertations, please use the following link to log into our proxy server with your WSU access ID and password, then click the "Off-campus Download" button below.
Non-WSU users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Access Type
WSU Access
Date of Award
January 2024
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
Eduard Y. Chekmenev
Abstract
Understanding the molecular transformations that underlie many diseases meansmonitoring the changes through metabolic pathways at the biomolecular level. Molecular imaging techniques such as MRI, positron emission tomography (PET), and mass spectrometry (MS) have become an indispensable tool for this purpose where compounds that are involved in metabolic pathways of certain diseases are detected and mapped. Of such techniques, MRI has the advantage of being non-invasive and non-destructive since it relies on the use of magnetic fields, radio waves and the inherent spin of nuclei in molecules to create images of tissues. However, MRI sensitivity is linearly proportional to the nuclear spin polarization (P) of the target nucleus. P is very low (10-5) at room temperature and clinically relevant magnetic field of 3T. Hyperpolarization techniques have been introduced to solve this problem by transiently increasing nuclear spin polarization using chemical and/or physical techniques which can then be used for enhanced molecular imaging as novel contrast agents. Among such techniques, Parahydrogen-Induced Polarization (PHIP) and Signal Exchange By Reversible Exchange (SABRE) and their variants offer a faster and cheaper alternative for production of hyperpolarized (HP) compounds that can be employed as metabolic contrast agents. These hyperpolarization techniques increase P by the addition of parahydrogen (p-H2) to a suitable substrate in hydrogenative PHIP or by reversible exchange with the substrate in the presence of a catalyst in SABRE. The result is an increase in nuclear spin order of protons in the target molecule which can also be transferred to heteronuclei X (13C, 15N, 31P) through spin-spin couplings using ultralow (<1 microtesla) static magnetic field. The transfer to heterenuclei is necessary to achieve longer relaxations times (i.e., the lifetime of hyperpolarized state), which is crucial to the clinical translation of the technique. The main goals of this work are the development of 1) the semi-automated clinical-scale parahydrogen generator; 2) the automated degaussing circuit for microtesla regime hyperpolarization; 3) automated and integrated microtesla hyperpolarizer; 4) novel contrast agents using parahydrogen-based SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) and magnetic field cycling (MFC) techniques. Achieving these aims will help in the biomedical translation of new contrast agents for molecular imaging.
Recommended Citation
Nantogma, Shiraz, "Instrumentation And Methods For Clinical-Scale Production Of Parahydrogen-Based Hyperpolarized Contrast Agents For Molecular Imaging" (2024). Wayne State University Dissertations. 3999.
https://digitalcommons.wayne.edu/oa_dissertations/3999
