Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references (leaves 122-135). Also available in electronic version.

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains xi, 104 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 99-104).

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.

There is increasing interest in the use of small field of view (SFOV) portable gamma cameras in medical imaging. A novel hybrid optical-gamma camera (HGC) has been developed through a collaboration between the Universities of Leicester and Nottingham. This system offers high resolution gamma and optical imaging and shows potential for use at the patient bedside, or in the operating theatre. The aim of this thesis was to translate the HGC technology from in vitro laboratory studies to clinical use in human subjects. Pilot studies were undertaken with the HGC as part of this thesis. Furthermore, efforts have been made to transform the HGC technologies into a new medical device, known as Nebuleye. Initial physical evaluation of the pre-production prototype camera was carried out as part of the device developmental process, highlighting some aspects of the design that require further modification. A complete and rigorous testing scheme to assess the pre-production prototype camera has been developed and successfully implemented. The newly introduced tests enabled the system uniformity, system sensitivity, detector head shielding leakage, optical-gamma image alignment and optical image quality of the hybrid camera to be assessed objectively. This harmonised testing scheme allows characterisation and direct comparison of SFOV gamma cameras. In vitro and in vivo preclinical imaging was undertaken to examine the performance of the SFOV gamma cameras for experimental animal studies. The results of animal study have shown for the first time the feasibility and performance of these SFOV gamma cameras for imaging mice injected with a newly developed 111In labelled hybrid tracer. Further investigations are needed to improve the system resolution and prepare the camera system for combined gamma-near infrared fluorescence imaging in future. A systematic in vitro laboratory assessment method has been established to examine the imaging performance of the SFOV gamma camera in radioguided sentinel lymph node biopsy (SLNB) and radioactive seed localisation procedures for breast cancer surgery. Further preparatory work was undertaken to carry out a pilot clinical trial of the use of the pre-production prototype camera in sentinel node localisation procedures during breast cancer surgery. The clinical study protocol and routine quality control procedures have been established and are suitable for future use. Baseline data on the camera performance assessed using the routine quality control scheme have been obtained. Finally, the capabilities of the SFOV gamma camera were assessed. This has provided baseline data on user feedback and the imaging consequences on operator motion effects, as well as examining the detectability of a range of radionuclides, including 99mTc, 111In, 123I, 125I and 75Se. The first clinical results of the use of the HGC in clinical hybrid optical-gamma imaging in patients administered with 99mTc and 123I labelled radiopharmaceuticals have been reported. This clinical study has demonstrated the feasibility and capability of HGC in various clinical applications performed at the patient bedside, which included patients undergoing bone, thyroid, lacrimal drainage and lymphatic imaging as well as DaTscan studies. In conclusion, the work in this thesis has demonstrated the successful translation of an SFOV hybrid gamma camera for clinical use. This system would be ideally suited for use in the operating theatre for radioguided procedures such as sentinel node detection and tumour localisation. This system also offers potential for use with the new generation of hybrid fluorescent-radionuclide tracers currently under development.

When performing nuclear magnetic resonance (NMR) it is desirable to maximise the available polarisation of the spin system in order to achieve optimal signal-to-noise ratios. One method of achieving this is via the process of spin-exchange optical pumping (SEOP). SEOP can be used to produce hyperpolarised (HP) noble gases, which possess numerous applications in the fields of science and medicine, ranging from spectroscopic imaging of porous media to Magnetic Resonance Imaging (MRI) of the human lungs. The SEOP process involves transfer of angular momentum from circularly polarised laser photons to the electrons of an alkali metal vapour. Noble gas nuclei can then be polarised via collisions with the alkali metal vapour. Ultra-low frequency Raman Spectroscopy may be used to perform rotational temperature measurements of a nitrogen buffer gas in these SEOP experiments in real-time, in an attempt to understand the poorly understood and highly complex system dynamics and energy transport processes. The work contained in this thesis aims to investigate the co-dependence of these dynamics, in order to characterise the SEOP process in greater detail for a variety of gas mixtures, temperatures and alkali metal targets. With this, it is hoped that HP noble gases may be produced with greater efficiency, achieving faster build-up rates and higher net magnetisation. In addition to in situ Raman spectroscopy, additional diagnostic techniques were implemented in order to illustrate the co-dependence of variables during the thermal exchange processes present in SEOP. Low-field NMR spectroscopy was utilised to determine the 129Xe net spin polarisation (P_Xe) as a function of time and position within the SEOP vessel, whilst near-infra-red (NIR) optical absorption spectroscopy allowed an estimate of the alkali metal polarisation and global pump laser power absorption to be determined. Additionally, initial studies into the use of optical absorption spectroscopy at various wavelengths for determination of the alkali metal number density are discussed. A chronology of experiments conducted using an `in-line', optically filtered Raman probe arrangement will be presented, culminating in the development of a fully automated, single-axis translational stage to perform rapid measurement of the rotational nitrogen temperature (T_N2) within the optical pumping cell with a high degree of temporal and spatial precision. The automated nature of the system facilitates a >3-fold improvement in the rate of thermal data acquisition, with greater ease and reliability than the previous manual method. In addition to pure rubidium, rotational temperature determination via Raman spectroscopy is demonstrated in a variety of rubidium/caesium hybrid alloy mixtures. In this way it may be possible to more efficiently utilise the greater spin exchange rate of caesium with 129Xe to achieve hybrid Rb/Cs cross-polarisation. The result of this is the first observation of 129Xe polarisation in a hybrid Rb/Cs system exceeding that of an equivalent pure Rb system under otherwise identical experimental conditions.

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Hyperpolarized 83Kr has previously demonstrated MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. One-dimensional nuclear magnetic resonance spectroscopy of hyperpolarized 83Kr has also revealed distinctive longitudinal relaxation times from selected regions of an ex vivo rat lung originating from differences in surface to volume ratio. However, at the time, MRI using longitudinal relaxation for contrast was not attempted due to limited signal intensities. Methodological advances of the spin exchange optical pumping process have led to a substantial increase in the 83Kr hyperpolarization and the resulting signal intensity. This methodology originates from a below-ambient pressure hyperpolarization technique explored and developed in this work. Using the improved methodology for spin exchange optical pumping of isotopically enriched 83Kr has resolved anatomical details of ex vivo rodent lungs using hyperpolarized 83Kr MRI for the first time. Different 83Kr longitudinal relaxation times were found between the main bronchi and the parenchymal regions of the lung. The T1 weighted hyperpolarized 83Kr MRI provided the first demonstration of surface quadrupolar relaxation pulmonary MRI contrast. Novel hyperpolarization techniques of 129Xe have also been explored resulting a study into the combustion process of methane. Using 129Xe as a probe into the combustion process permitted the first in situ MRI of combustion and enabled spatial-velocity profiles.