Magnetisation Transfer Contrast (MTC) is a well-established magnetic resonance imaging (MRI) contrast-generating mechanism, and is widely used for clarifying MR-invisible macromolecular information indirectly via MR-detectable free protons using an offresonance pre-saturation radiofrequency (RF) pulse (or MT pulse). As a result of MT pulse irradiation, magnetisation between both proton pools is exchanged and the signal intensity of mobile protons is decreased in relation to the amount of macromolecules. MTC MRI is normally implemented at a fixed magnetic field; however, it may be useful to evaluate changes of the MT effect as a function of magnetic field (B0). In order to explore fielddependent MTC experiments using a single MR instrument, two techniques are required, which enable simultaneously shifting both B0 and the resonance frequency of an RF coil (f0) during MT pulse irradiation and returning them to the original condition during MR data acquisition. Switching of B0 is achieved by fast field-cycling (FFC). FFC is a novel technique allowing B0 to shift between levels rapidly during the pulse sequence. This makes it possible to perform a number of beneficial field-dependent studies and/or to provide new MR contrast mechanisms. Switching of f0 requires an actively frequencyswitchable RF coil. This coil was designed and constructed for frequencies at and below 2.5 MHz proton Larmor frequency. The design employed PIN diodes, and enabled switching f0 between five different values. Using these techniques and tools, fielddependent MTC experiments were carried out with a control sample and samples with different concentrations of agarose gel. Due to the absence of macromolecules in the control, the MT effect was almost zero, whereas the MT effect observed in agarose samples increased with increasing concentration of macromolecules. Furthermore, MT effects ((for a given set of MT pulse conditions) were larger at higher B0.

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.

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.

No description available.

The major work involved is the debugging procedure on the Varian Model V-21003 electromagnet, power supply and spectrometer and the design and construction of supporting structure to house the various pieces of apparatus which were required to complete the system.Equipment which was not immediately available was then designed and constructed, with the final step being the testing. of the entire system for its integrity.Adjustments to each component was then carried out to obtain the best signal possible, noting the various changes caused by the condition and setting of each section of the system.

This thesis comprises a computer analysis of NMR-determined interatomic distance in strontium formate dihydrate. The computer program is designed to locate the hydrogen atoms associated with the water molecules in strontium formate dihydrate. The bond length of the oxygen-hydrogen bond is assumed to be fixed. The program varies the hydrogen separation, plotting total proton interaction against the hydrogen separation distance. Using Van Vleck's second moment theory, the hydrogen-hydrogen distances were determined.. The value of the second moment of the NMR absorption curve is 24.6 gauss2, obtained from investigation by Dr. D. E. Koltenbah. The result of this thesis is that the proton separation is 1.47± .02 A. This result is found to be close enough to other studies to conclude that the program analysis is essentially sound.

Multidimensional nuclear magnetic resonance (NMR) spectroscopy has become one of the most important techniques available for studying the structure and function of biological macromolecules at atomic resolution. The conventional approach to multidimensional NMR involves the sampling of the time domain on a Cartesian grid followed by a multidimensional Fourier transform (FT). While this approach yields high quality spectra, as the number of dimensions is increased the time needed for sampling on a Cartesian grid increases exponentially, making it impractical to record 4-D spectra at high resolution and impossible to record 5-D spectra at all. This thesis describes new approaches to data collection and processing that make it possible to obtain spectra at higher resolution and/or with a higher dimensionality than was previously feasible with the conventional method. The central focus of this work has been the sampling of the time domain along radial spokes, which was recently introduced into the NMR community. If each radial spoke is processed by an FT with respect to radius, a set of projections of the higher-dimensional spectrum are obtained. Full spectra at high resolution can be generated from these projections via tomographic reconstruction. We generalized the lower-value reconstruction algorithm from the literature, and later integrated it with the backprojection algorithm in a hybrid reconstruction method. These methods permit the reconstruction of accurate 4-D and 5- D spectra at very high resolution, from only a small number of projections, as we demonstrated in the reconstruction of 4-D and 5-D sequential assignment spectra on small and large proteins. For nuclear Overhauser spectroscopy (NOESY), used to measure interproton distances in proteins, one requires quantitative reconstructions. We have successfully obtained these using filtered backprojection, which we found was equivalent to processing the radially sampled data by a polar FT. All of these methods represent significant gains in data collection efficiency over conventional approaches. The polar FT interpretation suggested that the problem could be analyzed using FT theory, to design even more efficient methods. We have developed a new approach to sampling, using concentric rings of sampling points, which represents a further improvement in efficiency and sensitivity over radial sampling. / Dissertation

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI/Dissertation Abstracts International.