Irwin, Robert
(2021)
Development of hyperpolarised xenon 129 production and MRI for a clinical setting.
PhD thesis, University of Nottingham.
Abstract
When the spin polarisation of a nuclear species' is increased far above levels observed at thermal equilibrium, it is said to be hyperpolarised (HP). These HP species can be created using many different methods for the purposes of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). HP Xenon 129 (129Xe) can be created using spin-exchange optical-pumping (SEOP), which uses circularly polarised light to polarise the electronic spins of alkali metal vapour. The polarised alkali metal electrons then transfer their polarisation to noble gas nuclei via Fermi contact two and three-body interactions. Other methods of HP are available such as dynamic nuclear polarization (DNP) and brute force (BF) polarisation.
One of the applications of HP 129Xe is clinical MRI imaging, which can be used to provide non-invasive structural and functional information about internal organs. This thesis focuses on 129Xe MRI for in-vivo lung imaging. This offers more sensitive localised information than spirometry, which can only provide an assessment of global lung function and does not provide localised structural or functional information. HP 129Xe MRI also does not use ionising radiation, unlike computerised tomography (CT) scans. CT and spirometry are the two most popular methods of assessing lung function and structure. This thesis examines the complete pathway of HP 129Xe production, from its polarisation to use in imaging, and starts by investigating the kinetics of 129Xe polarisation (PXe) inside the optical cell where SEOP takes place. This analysis was conducted by measuring PXe using low-field NMR in tandem with in-situ Raman spectroscopy to measure the in-cell N2 gas temperature. The ability of 4He to reduce thermal gradients across the cell was found to have no significant effect on the N2 temperature and PXe when using an alkali metal with a high surface area within a cylindrical optical cell with a 1-inch diameter. Furthermore, the first comparison of internal gas temperatures during SEOP when using Rb and Cs as the alkali metals of choice was undertaken. It showed that Cs entered alkali metal runaway at an oven temperature of 120 C and above, with N2 temperatures elevated in excess of 330 C, whereas, under identical conditions, the N2 temperature in an Rb cell remained stable, slightly above oven temperature. The PXe measurements also exhibited the results seen in previous studies, namely that, under optimal conditions, Cs can achieve up to twice the PXe that could be produced with Rb.
Additionally, the upgrade, redesign and testing of a stopped-flow hyperpolariser (N-XeUS2) intended for clinical use is described. The N-XeUS2 is based on the XeNA, XeUS and N-XeUS designs, which were previously developed by the consortium (University of Nottingham, Southern Illinois University Carbondale and Vanderbilt University) to scale up HP 129Xe production for a clinical setting. The upgrade and redesign were aimed at improving reliability, ease of use and cell lifetimes. This process involved redesigning the gas handling manifold, modifying the automation code and testing a 200 W laser at 794nm (Micro-channel cooled (MCC), QPC, Sylmar California, USA). The XeUS2 design was tested at Wayne State University, where the W-XeUS2 polariser was able to achieve a record PXes in a 2000 Torr cell of 59 ± 1.5%, 76 ± 2% and 98 ± 1.9% at Xe partial pressures of 1500, 1000 and 500 Torr, respectively. A long-term quality assurance (QA) study was undertaken on the W-XeUS to investigate its cell lifetime. It was found that useable PXe levels could still be produced even after ≈ 700 optical cell fills, equivalent to one to two years of typical use. This was the first study of its type on this polariser design.
The work from later chapters presented in this thesis took place in the Queens Medical Centre (QMC) in Nottingham and focuses on producing and imaging HP 129Xe in a clinical setting. The HP 129Xe produced in the QMC was undertaken using a Polarean 9810 continuous-flow polariser. An investigation looked at the PXe that could be produced with a 3% Xe gas mix at different flow rates through the optical cell. At clinically relevant time scales, the Polarean 9810 could produce a 1 L sample in 28 minutes, with a PXe of ≈ 16.7%.
The HP 129Xe in the QMC was generated for use on both a 0.5 T MROpen Upright Paramed Medical Systems (Upright) scanner and a General Electric (GE) 1.5 T HDx multi-nuclear Flatbed MRI scanner. The Upright scanner's open geometry increases its tolerability, increasing the cohort of patients that can be imaged in any orientation. Using the Upright scanner and a small surface coil manufactured by Clinical MR Solutions (CMRS), the first HP 129Xe imaging study was performed. It showed that the coil and scanner together could resolve millimetre-level detail when imaging a phantom filled with HP 129Xe. The setup was also able to perform dissolved-phase NMR and could clearly resolve the NMR peaks of 129Xe dissolved in water, olive oil, tert-butanol and ethanol. These NMR and MRI results indicated that, once the coil is approved for human use, it could be used to perform initial in-vivo 129Xe MRI lung imaging on the Upright scanner.
A new flexible chest coil from CMRS (CMRS coil) designed for use with the GE 1.5 T flatbed MRI scanner was procured and tested to determine whether it could act as a suitable replacement for the previously rigid chest coil made by Rapid biomedical. In quadrature transmit array receive (QTAR) mode, a drop in signal from anterior to posterior was observed, making it unfit human for use. The coil was then switched to Quadrature Tx array Rx (QUAD T/R) mode, which gave more consistent results under initial testing. The flexible coil design allows for larger volunteers to be images increasing the limited cohort of patients that could tolerate the previous rigid coil.
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