Spin dynamics of nuclear singlet-states: application to parahydrogen induced hyperpolarization

Abstract

Nuclear magnetic resonance (NMR) harnesses the sensitive dependence of nuclear spin dynamics to detect molecular structure and interaction with environments. At ambient temperature and 3 Tesla field, the signal acquired arises from a low polarization near 10-5 range, which is generally insufficient to detect important events such as flux through metabolic pathways. A variety of techniques has started to emerge to enhance the polarization. The most developed technology, DNP (dynamic nuclear polarization) has demonstrated sufficient sensitivity to detect and monitor response to therapy in tumors, but it suffers from high expense and instrumental bulk. These shortcomings spur development in alternative methods such as PHIP (parahydrogen induced polarization). PHIP achieves similar enhancement levels at significantly reduced instrumental complexity and expense, but to be useful for applications to biomedicine, developments in several key areas will be required for PHIP to rival the success of DNP.

In this dissertation, developments of three PHIP technologies were undertaken to improve the range of application and the efficiency of PHIP. More specifically, methods were developed for efficiently converting singlet-states (unobservable) into a form that could be imaged with standard imaging sequences. These sequences were developed analytically for 3 spin (I1I2S) systems that efficiently transfer polarization regardless of scalar coupling topology. New precursors are in development that yield 4 spin I1I2SR systems, but no sequences are currently available to convert spin order efficiently for them. An efficient sequence is described that enables approximately unity polarization to be transferred in these molecules. Finally, the efficiency of these processes depends on accurate knowledge of the scalar couplings, which are sensitive to the conditions to generate PHIP reagents, but the fields where the experiments are most efficient are not adequately resolved to measure them. A method was developed for performing high resolution spectroscopy at low inhomogeneous fields. These techniques together provide suite of efficient tools that will enable high PHIP polarization to be harnessed in a form that can be readily detected with standard imaging techniques.