Low-field NMR and MRI using in situ parahydrogen hyperpolarisation

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Magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) spectroscopy are powerful tools for applications that range from synthetic chemistry to medical diagnosis. However, these methods suffer from low sensitivity because only tens out of every million atomic nuclei in the sample being studied are actually detected. For example, the fraction of the 1H nuclei that are detected in standard NMR experiments is approximately 3.5 ppm for every Tesla of magnetic field that is applied. Therefore, only relatively large quantities of substances can be investigated and expensive high-magnetic-field devices are required. One promising route to dramatically improving magnetic resonance is through the use of hyperpolarisation. This is the name given to methods that increase the fraction of detected nuclei by perturbing the nuclear spin state populations far from equilibrium. One of the areas of magnetic resonance made possible by hyperpolarisation is the use of low-cost NMR and MRI devices that generate the necessary magnetic field using either simple electromagnets (tens of mT) or even the Earth's magnetic field (50 uT). The aims of this project are to develop optimised hyperpolarisation strategies for uT-mT NMR and MRI and to explore the potential applications of this technology, particularly as a low-cost analytical tool for industrial use. The focus will be on the SABRE (signal amplification by reversible exchange) method, which uses a form of hydrogen gas known as parahydrogen (p-H2), to generate the hyperpolarisation effect. Specifically, SABRE uses a transition metal complex to catalytically transfer polarisation from parahydrogen (the singlet nuclear spin isomer of H2) to a molecule of interest in solution thereby increasing the detectability of the target molecule by many orders of magnitude. A key feature of SABRE is that the exchange reaction step, where the polarisation transfer takes place, must be carried out in a very low field of a few mT in order for the transfer to be efficient. In the standard approach, SABRE polarisation transfer is achieved over a period of seconds in a mT field (called the polarisation transfer field or PTF) and then the sample is transported (either manually or under flow) to the NMR spectrometer for signal detection at a much stronger field (> 1T). In this project, the SABRE polarisation transfer and the subsequent NMR detection will be carried out in situ, without the need to shuttle the sample between two different fields. The in situ approach will be exploited to directly probe the polarisation transfer process and so obtain new physical insights into the SABRE technique for a range of chemical systems. These insights will be used to design and implement new methods for optimising polarisation transfer, particularly for diagnostically important nuclei such as 13C. The optimised hyperpolarisation methods will then be used to develop novel methods to obtain chemically diagnostic information in the uT - mT regime, where chemical shift resolution is unavailable. This will include the use of imaging as well as NMR parameters such as molecular self-diffusion, heteronuclear scalar (J) coupling, and NMR relaxation rates to differentiate the hyperpolarised responses from different chemical species.