Spin-exchange optical pumping (SEOP) is a hyperpolarisation method used in the hyperpolarisation of noble gases and can enhance nuclear spin polarisation by five orders of magnitude. Hyperpolarised (HP) 129-Xe has many properties that make it ideally suited to clinical lung imaging, but since its first demonstration in animals in 1994 and humans in 1996, translation to the clinic has been hampered by challenges associated with scaling up production. Within this thesis, construction and demonstration of a clinical-scale stopped-flow hyperpolariser is described, the design of which is based on the record holding XeUS and XeNA polarisers developed previously by our consortium, which had aimed to address the issue of production scale-up. Modifications enhancing the ease of operation and utility in-clinic are presented, as are modifications that reduce the capital cost of such a system. These include a re-design of the gas manifold and the development of a low-cost low-field NMR spectrometer which achieved an SNR of 125 at a cost of ~$300, a 13-fold improvement in cost/SNR compared with the existing spectrometer at a saving of ~$19,000. In continuous-flow 129-Xe polarisers there has long been a discrepancy in the polarisation achieved and that predicted by the standard model of SEOP which was shown recently to be due to the presence of rubidium clusters. Here, the standard model is applied to- and validated for the first time against the stopped-flow regime. The validated model is used to explore parameter space to identify the most effective ways to increase production yield in future stopped-flow polarisers. Stopped-flow SEOP in the xenon-rich regime presents unique thermal management problems due to the absence of gas flow and abundance of poorly thermally conductive, Rb spin destroying Xe. Raman spectroscopy is used to spatially examine in-cell thermal behaviour under steady-state and turbulent 'rubidium runaway' conditions as a function of temperature and Xe density and the beneficial impact of adding thermally conductive helium to the standard N2-Xe gas mix is demonstrated. Hybrid Rb-Cs-Xe SEOP is demonstrated for the first time and examined using in-situ NMR and Raman spectroscopies. High polarisations of ~50% were obtained. Finally, progress on the HP-Xe clinical trial is presented to illustrate the impact of the 4-fold increase in SNR that will come with the installation of the new N-XeUS stopped-flow polariser.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:728460 |
| Date | January 2017 |
| Creators | Skinner, J. G. |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/41416/ |
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