Cardiovascular disease (CVD) is a term used to describe a variety of diseases and events that impact the heart and circulatory system. CVD is the United Kingdom's (UKs) biggest killer, causing more than 50,000 premature deaths each year. Early recognition of the potential for magnetic resonance imaging (MRI) to provide a versatile, non-ionising, non-invasive, technique for the assessment of CVD resulted in the modality becoming an area of intense interest in the research, radiology and cardiology communities. The first half of this thesis reviews some of the key developments in magnetic resonance hardware and software that have led to cardiac magnetic resonance imaging (CMRI) emerging as a reliable and reproducible tool, with a range of applications ideally suited for the evaluation of cardiac morphology, function, viability, valvular disease, perfusion, and congenital cardiomyopathies. In addition to this, the advantages and challenges of imaging at 3.0T in comparison to 1.5T are discussed. The second half of this thesis presents a number of investigations that were specifically designed to explore the capability of CMRI to accurately detect subtle age and disease related changes in the human heart. Our investigations begin with a study at 1.5T that explores the clinical and scientific significance of the less frequently used measure of right ventricular function to test the hypothesis that the inclusion of this data provides a more informative assessment of overall cardiac function. The focus then shifts to imaging at 3.0T and the challenges of optimising cardiac imaging at this field strength are discussed. Normal quantitative parameters of cardiac function are established at this field strength for the left ventricle and the left atrium of local volunteers. These values are used to investigate disease related changes in left ventricle and left atrium of distinct patient cohorts. This work concludes by investigating the impact of gadolinium-based contrast agents on the quantitative parameters of cardiac function.

The initial aim of this project was to improve the performance of a chromatographic bioreactor-separator (CBRS). In such a system, a dilute enzyme solution is pumped continuously through a preparative chromatographic column, while pulses of substrate are periodically injected on to the column. Enzymic reaction and separation are therefore performed in a single unit operation. The chromatographic columns used were jacketed glass columns ranging from 1 to 2 metres long with an internal diameter of 1.5 cm. Linking these columns allowed 1, 2, 3 and 4 metre long CBRS systems to be constructed. The hydrolysis of lactose in the presence of β~galactosidase was the reaction of study. From previous work at Aston University, there appeared to be no difficulties in achieving complete lactose hydrolysis in a CBRS. There did, however, appear to be scope for improving the separative performance, so this was adopted as an initial goal. Reducing the particle size of the stationary phase was identified as a way of achieving this improvement. A cation exchange resin was selected which had an average particle size of around half that previously used when studying this reaction. A CBRS system was developed which overcame the operational problems (such as high pressure drop development) associated with use of such a particle size. A significant improvement in separative power was achieved. This was shown by an increase in the number of theoretical plates (N) from about 500 to about 3000 for a 2 metre long CBRS, coupled with higher resolution. A simple experiment with the 1 metre column showed that combined bioreaction and separation was achievable in this system. Having improved the separative performance of the system, the factors affecting enzymic reaction in a CBRS were investigated; including pulse volume and the degree of mixing between enzyme and substrate. The progress of reaction in a CBRS was then studied. This information was related to the interaction of reaction and separation over the reaction zone. The effect of injecting a pulse over a length of time as in CBRS operation was simulated by fed batch experiments. These experiments were performed in parallel with normal batch experiments where the substrate is mixed almost instantly with the enzyme. The batch experiments enabled samples to be taken every minute and revealed that reaction is very rapid. The hydrodynamic characteristics of the two injector configurations used in CBRS construction were studied using Magnetic Resonance Imaging, combined with hydrodynamic calculations. During the optimisation studies, galactooligosaccharides (GOS) were detected as intermediates in the hydrolysis process. GOS are valuable products with potential and existing applications in food manufacture (as nutraceuticals), medicine and drug targeting. The focus of the research was therefore turned to GOS production. A means of controlling reaction to arrest break down of GOS was required. Raising temperature was identified as a possible means of achieving this within a CBRS. Studies were undertaken to optimise the yield of oligosaccharides, culminating in the design, construction and evaluation of a Dithermal Chromatographic Bioreactor-separator.

Fast field-cycling MRI (FFC-MRI) is a novel technique that promises to expand upon the diagnostic capabilities of conventional MRI by allowing the main magnetic field, B0, to be varied during the imaging pulse sequence. By doing this it is possible to gain access to information that is hidden to conventional scanners - namely the variation of the spin-lattice relaxation time, T1, with field strength, known as T1 dispersion. However, adding B0 as a new dimension to the imaging process necessitates a longer scan time which can limit the techniques application to clinical research. In this thesis, several methods are explored for reducing FFC-MRI scan times. A rapid imaging pulse sequence based on the well-known Fast Spin-Echo imaging sequence is presented, as well as an adaptation of the “keyhole” acquisition strategy. A method of determining T1 which requires significantly less data - and hence scan time - is also presented. When combined, these techniques are demonstrated to reduce total scan time from several hours to minutes without compromising access to T1 dispersion information. The techniques are demonstrated in phantom studies and in vivo results from volunteers are presented as proof of concept. The reduction in scan time demonstrated by these methods will significantly improve the applicability of FFC-MRI for clinical trials which are currently being worked towards.

NMR spectroscopy is a powerful technique that allows the study of short-range electronic effects and local structure. The aim of the work has been to separate and manipulate the many different interactions so that they can be individually measured. For this we have used multinuclear techniques and probes. We have measured a range of spectra for different organotin, iminophosphorane and lithium compounds. We have obtained a selection of spectra including (^19(F {(^1)H} and doubly-decoupled (^119)Sn {(^1)H, (^19)F} for the organotin fluorides (^n)Bu(_3)SnF, Mes(_3)SnF, SnF(_2), Me(_2)SnF(_2), and (^n)Bu(_2)SnF(_2). These have been used to calculate the effective shielding anisotropies, asymmetries, effective dipolar coupling (D'), and the anisotropy in the indirect coupling (∆J), using analyses of the spinning-sideband manifolds. Simulation programs have been written to simultaneously fit multiple sets of data, which reduce the fitting errors and give the relative orientations of the tensor interactions. The (^19)F chemical shifts, indirect coupling (^1)j(SnF) and (^1)∆J(SnF) data have been summarised. For (^n)Bu(_2)SnF(_2), a structure has been proposed based on comparisons with the NMR results from the other compounds. For the iminophosphoranes, the dipolar tensor and its orientation can be measured from the (^31)P static spectrum, whilst in the MAS spectrum residual dipolar coupling lineshapes are visible. These give information about the electric dipole nature of the P-N bond and the nature of its bonding. For the lithium nuclei, the quadrupolar interaction is small, but can be directly studied. With the two NMR-active isotopes both tire shielding and quadrupolar interactions can be measured. Ab initio calculations have been used to calculate certain NMR parameters such as the shielding, quadrupolar and indirect coupling tensors from the molecular structure. Experimental data have been compared against tlie calculations to verify the accuracy of the model. At present, there is good agreement between experimental and calculated results for (^6,7)Li, (^13)C, (^14,15)N and (^31)P, though (^119)Sn remains a challenge.

This thesis deals with the synthesis of dendritic gadolinium complexes based on DOTA, with a view to obtaining enhanced relaxivities. Li addition to the inherently long electronic relaxation time and high paramagnetic moment of the gadolinium (III) ion, the speed of rotation of its complexes in solution is a decisive parameter in the determination of the relaxivity. This parameter is dependent on the molecular mass of the complex. Initially, the enantioselective synthesis of novel a-substituted analogues of DOTA was attempted but was not successful due to difficulties encountered in attaining the tetraalkylation of cyclen and the purification of the products obtained. Therefore, further studies were carried out based on the known [Gd(gDOTA)]" system. The synthesis of three medium M(_W) dendrons, each with a focal primary amino group was carried out. Their structures may be described as dendrimeric analogues of poly(ethylene glycol). Two of these structures were successfully coupled to the gadolinium (III) chelate, [Gd.gDOTA]. The acid-catalysed epimerisation of the statistical distribution of stereoisomers yielded solely the (RRRR)/(SSSS) isomeric pair. This system had previously been shown to undergo fast water exchange. The coupling and deprotection procedure yielded paramagnetic dendritic complexes with molecular weights of 2013 and 3535.Relaxivity measurements were carried out on these systems and the results showed significantly higher relaxivities of 18 and 21 mM(^-1) s(^-1) respectively, compared with a value of 7.8 mM(^-1) s(^-1) for the parent compound. Examination of NMRD profiles for the larger system showed a decrease in the rotational correlation time to 310 ps at 298 K, as expected. However, this was accompanied by an increase in the inner-sphere water exchange lifetime to 570 ns at 298 K. Therefore, although an improvement in relaxivity was obtained through a coupling to the slower rotation of the system in solution, this enhancement was limited by the accompanying decrease in the rate of water exchange. The best fitting procedure of the NMRD profiling procedure revealed the presence of 8 second-sphere water molecules at an average distance of 4Å. The second sphere contribution was shown to be the dominant contributor to the overall relaxivity. This accounted for >50% of the increased relaxivity.

Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 100-103.

by Lee Hon Shing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 105-106). / Text in English; abstracts in English and Chinese. / by Lee Hon Shing. / Acknowledgements --- p.i / Abstract --- p.ii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Theory --- p.4 / Chapter 2.1 --- Radiation pressure on a microdroplet --- p.5 / Chapter 2.2 --- Mie scattering theory --- p.8 / Chapter 2.3 --- Laser levitation of a microdroplet --- p.11 / Chapter Chapter 3 --- Dual wavelength experiment --- p.14 / Chapter 3.1 --- Introduction --- p.15 / Chapter 3.2 --- Experiment --- p.16 / Chapter 3.2.1 --- Dual wavelength experiment --- p.16 / Chapter 3.2.2 --- Measurement of the levitating laser beam waist --- p.20 / Chapter 3.2.3 --- Measurement of the levitating laser beam profile --- p.22 / Chapter 3.3 --- Data analysis and results --- p.25 / Chapter 3.3.1 --- Deducing the size of a microdroplet by exploiting Ib(t) and Ig(t) --- p.27 / Chapter 3.3.2 --- Intensity as functions of size parameter --- p.32 / Chapter 3.3.3 --- Vertical position as a function of size parameter --- p.39 / Chapter 3.3.4 --- Comparison between experimental and theoretical results --- p.43 / Chapter 3.3.5 --- Broadening of MDRs --- p.55 / Chapter 3.3.6 --- Fine correction factor --- p.60 / Chapter Chapter 4 --- Deformation of a laser-levitated water microdroplet --- p.63 / Chapter 4.1 --- Introduction --- p.64 / Chapter 4.2 --- Experiment --- p.65 / Chapter 4.2.1 --- Dual wavelength experiment --- p.65 / Chapter 4.2.2 --- Double-slit experiment --- p.65 / Chapter 4.3 --- Data analysis and results --- p.68 / Chapter 4.3.1 --- """Cross-talk"" in dual wavelength experiment" --- p.69 / Chapter 4.3.2 --- MDR-induced oscillation of a laser-levitated water mircodroplet in dual wavelength experiment --- p.74 / Chapter 4.3.3 --- MDR-induced oscillation of a laser-levitated water mircodroplet in double-slit experiment --- p.81 / Chapter Chapter 5 --- Step-function levitation force experiment --- p.85 / Chapter 5.1 --- Introduction --- p.86 / Chapter 5.2 --- Step-function levitation force experiment --- p.87 / Chapter 5.3 --- Data analysis and results --- p.90 / Chapter 5.3.1 --- Deducing the size of the microdroplet by its vertical position --- p.91 / Chapter 5.3.2 --- Intensity curves of the step-function levitation force experiment --- p.95 / Chapter Chapter 6 --- Conclusion and future outlook --- p.99 / Chapter 6.1 --- Conclusion --- p.99 / Chapter 6.2 --- Future outlook --- p.101 / Appendix A --- p.103 / Appendix B --- p.104 / References --- p.105

Fu Pengpeng. / Thesis submitted in: August 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 98-98). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.iii / Table of Contents --- p.vii / List of Figures --- p.xii / List of Tables --- p.xiii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Background --- p.1 / Chapter 1.2 --- A Simple 2-D Mie Scattering Model --- p.2 / Chapter 1.3 --- Topics in the Following Chapters --- p.7 / Chapter 2 --- Beam-shape Coefficients for 2-D Monochromatic Laser Beam --- p.9 / Chapter 2.1 --- General Case --- p.9 / Chapter 2.2 --- Plane Wave Case --- p.13 / Chapter 2.3 --- General Case of An Arbitrary Beam --- p.15 / Chapter 3 --- "Modified Explicit Asymptotic Formulas for the Positions, Widths of Resonances in 2-D Mie Scattering" --- p.17 / Chapter 3.1 --- Introduction --- p.17 / Chapter 3.1.1 --- Positions --- p.19 / Chapter 3.1.2 --- Widths --- p.20 / Chapter 3.2 --- Positions of Resonances --- p.21 / Chapter 3.2.1 --- Derivation --- p.21 / Chapter 3.2.2 --- Numerical Comparison --- p.28 / Chapter 3.2.3 --- Separation --- p.30 / Chapter 3.2.4 --- Conclusion --- p.32 / Chapter 3.3 --- LineWidth --- p.32 / Chapter 3.3.1 --- TE Mode --- p.34 / Chapter 3.3.2 --- TM Mode --- p.36 / Chapter 3.3.3 --- Conclusion --- p.38 / Chapter 3.4 --- Conclusion --- p.39 / Chapter 4 --- Effects of Surface Perturbation of 2-D Mie Scattering --- p.42 / Chapter 4.1 --- Experimental Background --- p.42 / Chapter 4.2 --- Theoretical Derivation --- p.44 / Chapter 4.3 --- Numerical Results --- p.57 / Chapter 5 --- Conclusions and Discussions --- p.79 / Appendix --- p.81 / Chapter A --- Approximate Solution to One Matrix Equation with Pertur- bation --- p.82 / Chapter B --- Airy Functions --- p.87 / Chapter C --- Bessel Functions --- p.89 / Chapter C.1 --- Basic Properties of the Bessel Functions --- p.89 / Chapter C.2 --- Numerical Evaluation of The Bessel Functions --- p.91 / Bibliography --- p.94

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