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.

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.

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 (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 89-90).

Thesis (Ph. D.)--University of Queensland, 2001. / Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xviii, 105 p.; also contains graphics (some col.). Includes abstract and vita. Advisor: David L. Clark, Dept. of Anatomy. Includes bibliographical references (p. 98-105).

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xxx, 268 p.: ill. Includes abstract and vita. Advisor: Robert Lee, Dept. of Electrical Engineering. Includes bibliographical references (p. 256-268).

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy