Signal Enhancement by the SABRE Method in High Magnetic Fields

In this thesis, I investigate the Signal Amplification by Reversible Exchange (SABRE) technique as a hyperpolarisation method to solve the MRI sensitivity problem and use it to study the interaction of hyperpolarised molecules with biological tissues. The fundamental issue in MRI and NMR is the very low sensitivity produced as a result of small population differences between nuclear spin states in a magnetic field. The main aim of my project is to develop imaging procedures for use in a human 3T MRI scanner with hyperpolarised samples and to investigate the use of spin hyperpolarisation in the study of biological processes in vitro. The objective is to understand, develop and optimise the use of the SABRE method of spin hyperpolarisation with a variety of biologically relevant molecules.
This thesis shows how the fringe field of the 3T magnet can be used for polarisation and how the time dependency of the decay of signals in the scanner can be investigated. In particular I investigated the non-exponential decay of the signals and have attempted to explain the origin of this decay. The observations show strong evidence that the signal from hyperpolarised Pyrazine decays with a non-exponential time course. The major evidence against this being turbulence is that the deviation from an exponential decay is field dependent. This has also been shown with Nicotinamide and with Pyridine. Further investigations show that exposing the sample to heart tissue shows faster decay (shorter T1) than the sample without tissue. It is postulated that this effect is due to binding to specific ion channels that leads to the change in T1. It is postulated that this could be exploited to develop a specific imaging method for tissue bound hyperpolarised molecules. Moreover, with longer imaging times, it was shown that a signal returned in the presence of tissue and that this was evidence of possible long-lived states.
The observations in the final chapter demonstrate progress in developing the exploitation of long-lived states. The SABRE method was used to create magnetisation in Pyridazine. This large signal was then converted into a singlet state and it is shown that this signal can be read out some time later. The long-lived state was used to store the signal for over three minutes. This was repeated with and without heart tissue in the NMR sample. The presence of biological tissue, added after the formation of the singlet state, resulted in an increased signal and it is argued that this is evidence of an interaction between the tissue and the hyperpolarised molecule, It is suggested that the singlet state evolves into observable magnetisation on interaction with the tissue and that this could form the basis of a unique imaging contrast storage and readout method for specific molecular-tissue interactions.