Low-field NMR and MRI with in situ parahydrogen hyperpolarisation

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. Hyperpolarisation methods amplify signals by several orders of magnitude by dramatically increasing the fraction of nuclei detected. By overcoming the sensitivity barrier in NMR and MRI, hyperpolarisation holds great transformative potential. This is particularly true for applications of low-cost and portable NMR and MRI, where devices have low magnetic fields, ranging from µT (Earth’s field) up to 2T (permanent magnet arrays,) and so suffer from significantly lower sensitivity than traditional NMR spectrometers based on superconducting magnets with fields of 7 T and above. This project concerns the application of hyperpolarisation to NMR in the very low-field range (µT – mT) and will focus on the implementation and optimisation of the hyperpolarisation as well as the development of new applications for hyperpolarised low-field NMR and MRI more generally.
In the project we will focus primarily on the SABRE (signal amplification by reversible exchange) approach to hyperpolarisation that was developed in York by Prof Simon Duckett, the director of the Centre for Hyperpolarisation in Magnetic resonance (CHyM). SABRE is a catalytic process for transferring polarisation from parahydrogen (the singlet nuclear spin isomer of H2) to a molecule of interest in solution. SABRE is an attractive hyperpolarisation approach, particularly for low-field NMR, because it benefits from fast polarisation times (seconds), high potential polarisation levels (approaching 100%) that are detection-field independent and a relatively simple experimental implementation. 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 detection fields. This will be implemented in two ways: first with NMR and MRI detection in the Earth’s magnetic field and second with NMR detection in the polarisation transfer field itself. The project will involve adapting currently available low-field NMR and MRI hardware to suit the purpose, the design and implementation of novel experiment protocols and the application of these new experiments to study and optimise the hyperpolarisation process for a range of chemical systems of potential interest to industrial process monitoring and/or clinical diagnosis.

All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills

The project will be carried out under the supervision of Dr Meghan Halse and will be based in the Centre for Hyperpolarisation in Magnetic Resonance (CHyM), a cutting edge research facility in the Department of Chemistry that specializes in the development of p-H2 based methodologies in liquid-state NMR, with a particular focus on the development of hyperpolarised agents for use in clinical MRI. Throughout the project the student will gain advanced training in MR based analytical chemistry with additional skills in the theoretical basis of NMR and MRI, advanced data analysis and NMR and MRI experiment design and implementation on a range of instruments. This project will be carried out within the context of the large multidisciplinary research program within CHyM and therefore, through participation in group meetings, the student will be exposed to the wide range of expertise within the centre including NMR spectroscopy, hyperpolarisation, MR theory, photochemistry, catalysis and kinetics.

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. Shortlisted applicants will be invited for an interview to take place at the University of York on either the 13 or 15 February 2018. Candidates will be asked to give a short presentation prior to their interview by an academic panel.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. This PhD project is available to study full-time or part-time (50%).