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No description available.

Fast Field-Cycling (FFC) MRI allows the magnetic field to be switched during an imaging scan. FFC-MRI can be used to exploit a characteristic of contrast agents, i.e. the variation of its spin-lattice relaxation time (T1) or rate (R1= 1/T1) with magnetic field in order to increase contrast. Contrast agents play an essential role in MRI, allowing improved diagnosis and delineation of diseased tissue. However, the R1, and hence the effectiveness of contrast agents, varies significantly with magnetic field. Thus, Fast Field-Cycling (FFC) MRI can be used to take advantage of this variation to improve image contrast, allowing more sensitive detection of the agent. In this project new contrast agents, developed by a collaborating group (Invento S.r.l., Italy) were investigated for use with FFC-MRI. R1 dispersion curves of samples containing a range of contrast agents were first obtained using both a commercial relaxometer and a home-built whole-body FFC-MRI system, and the accuracy of the home-built FFC-MRI system was verified. The magnetisation behaviour of these samples during field-cycling pulse sequences was modelled in order to predict the pulse sequence parameters necessary for maximum T1 contrast. Images were obtained, using a number of novel imaging techniques developed on the home-built whole-body FFC-MRI system, and also, using standard T1 weighted imaging on a 3 T Philips clinical MRI scanner. A new FFC-MRI imaging method, ΔR1 mapping was employed to show an increase in contrast using a novel Mn2+ based liposomal contrast agent compared with T1 weighted images at 5 mT, 59 mT and 3 T. The low concentrations of Mn2+ based liposomal contrast agents used with ΔR1 mapping indicate suitability for molecular imaging

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.

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.