Lighting up Magnetic Resonance: SABRE optimisation powered by in situ detection

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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. This means that 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 (parts per million) 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 increasing the fraction of detected nuclei by factors of up to 100,000. In this work we focus on a method called SABRE (signal amplification by reversible exchange), which uses a special form of hydrogen gas, called parahydrogen (p-H2), to generate the hyperpolarisation effect. SABRE uses a transition metal complex to catalytically transfer polarisation from the p-H2 gas to a molecule of interest. This method has many exciting applications. For example, in clinical MRI, hyperpolarised agents have been injected into patients and then tracked to obtain diagnostic information about function and/or disease. This is only made possible by the hyperpolarisation, which allows the relatively small amount of the injected agent to be detected against the background of all of the other molecules in the body. Compared to other approaches, SABRE is a relatively new technology and so the underlying fundamental physics of the polarisation transfer process from p-H2 to the target molecule is poorly understood. Many theoretical models have been proposed but their simplifying assumptions are very difficult to test experimentally. This is because, in the standard approach, the detection stage of the SABRE experiment is separated in time and space from the polarisation stage, making direct interrogations of the transfer process challenging. Understanding SABRE is important not simply as an academic exercise. In order to transform SABRE into a universal hyperpolarisation technique, an efficient route to optimising the polarisation of new target molecules is required. Current empirical optimisation methods are time consuming, expensive, and not guaranteed to work. The central hypothesis of this work is that direct measurements of the SABRE effect carried out in situ - that is under the same conditions of magnetic field as where the polarisation transfer takes place - are the best route to developing a rigorous model for SABRE and thus enabling rational and rapid optimisation going forward. In this project, we will assemble a low-field (1 - 20 mT) NMR instrument that can be used as a platform to directly study the polarisation transfer process at the heart of SABRE. These experimental results will be combined with theoretical insights in order to devise a rigorous model that takes into account the many complexities of the SABRE process. This will lead to new strategies for polarisation transfer optimisation and consequently to an increase in the scope of SABRE applications in areas like medicine and industrial manufacturing.