High image fidelity in Magnetic Resonance Imaging (MRI) relies on precise magnetic field control of encoding gradient fields and background B0 magnetic fields. To ensure a high degree of accuracy in the spatial location of the proton spins and the resultant object geometry, conventional image encoding using linear gradient fields, as well as advanced techniques with non-linear encoding, requires field generating hardware capable of excellent field shaping capabilities and accuracy. Non-homogeneous B0 background fields in MR imaging cause faster relaxation, signal dropout, and geometry distortion, resulting in inferior image quality and reduced diagnostic accuracy. Besides manufacturing imperfections in the magnet and site conditions, the magnetic field inside the imaging object is not homogeneous due to the differences in geometries and magnetic properties of individual human tissues, which is recognized as the primary source of B0 variation in MRI. Considering the differences of B0 conditions across subjects, it is essential for MR imaging to utilize flexible B0 shimming techniques such as active shimming in order to produce a highly homogeneous B0 field. The control capability and optimized control strategy for these magnetic fields require the development of new hardware and methodologies. B0 background field generated by the magnet and the encoding gradient field from gradient coil are two critical pillars of MR imaging. Since the multi-coil array provides advanced shim capability and is proven to be capable of imaging encoding with a compact size, it is considered a perfect component as a combination of B0 shim coil and encoding gradient coil for an accessible head-only MR scanner. MR scanners like this type provide unique features that will enable researchers to develop new MRI methodologies and conduct research into the functionalities of the human brain through more natural human behaviors. Its clinical applications will be more accessible to the general population for disease screening and diagnosis due to its portability and low energy requirements. Since the multi-coil array has the advantage of smaller volume and wall thickness than the traditional gradient coil, its design and implementation is challenging because of its compact space, irregular curved shape of coil elements, mechanical reliability requirements during scan and good thermal control for long working periods. It was the challenges involved in the design and implementation of the multi-coil array that initiated the first project of my dissertation. In this project, we present 1) a novel molding method for the construction of resin-impregnated wire patterns with irregular curved shapes along with a microcontroller-driven motorized machine for automated coil construction, 2) the design and validation of a water-cooling system using multiple parallel pipes impregnated with thermal epoxy, 3) a quality-controlled procedure of building the multi-coil array employing the technique of vacuum resin infusion. A multi-coil array was fabricated successfully and evaluated in multiple sites and then integrated into the first-prototype of the accessible head-only MR scanner. The similar quality of experimental images from the fabricated multi-coil array compared to those from conventional gradient coils indicates that the multi-coil array can effectively shape fields for both image encoding and B0 shimming. Our lab has shown that multi-coil technology offers advanced shim capability when imaging the human brain, but it could potentially benefit the imaging of other organs like the heart. The MR imaging of the heart is subject to dark band artifacts or signal loss caused by B0 inhomogeneity, which can result in misinterpretation of lesions and a reduction in diagnostic accuracy. It has been demonstrated in a recent study that the use of multi-coil techniques can significantly reduce B0 inhomogeneity within the heart based on shim analysis using in vivo B0 maps. Multi-coil arrays are not a standard configuration in commercial scanners but are normally used for research, B0 shimming is typically implemented by using the commonly-installed spherical harmonic shim coils in the first, second, and potentially third orders. The development of multi-coil technology, more in-depth design of the coil structure and geometry as well as the optimal use of the current spherical harmonic shim technology require a thorough understanding of cardiac B0 conditions across subjects and at a population level. Since the in vivo cardiac B0 measurement is not a routine clinical protocol and dedicated in vivo measurement for a large sample size are extremely labor intensive and expensive, the lack of such B0 data is a long-standing problem, especially for the subject groups like pediatric or elderly patients who cannot undergo B0 map measurement with breath hold. This challenge could be resolved by the use of B0 simulation on the basis of structural images from different imaging modalities, assuming that the B0 distributions inside the human heart depends on the anatomical structures surrounding heart and across the entire body. The challenge and assumption led to my second project regarding B0 magnetic field simulation in the human heart. We proposed a novel B0 simulation approach based on chest-abdomen-pelvis structural CT images and validated it using in vivo acquired B0 maps in the heart from the same subjects. This B0 simulation approach was then applied to CT images from more than one thousand subjects and the resultant large set of simulated B0 maps were analyzed with different shim types for searching optimal shim solution based on popular spherical harmonic decomposition. The derived B0 conditions were also statistically analyzed for potential correlation and linear association with demographic parameters of these subjects for investigating potential population-based shim strategy. By the use of in vivo acquisition, we also investigated the B0 magnetic field variation across cardiac cycle and evaluated the impact of these variations on in vivo cardiac B0 shimming. The results of this study allow us to better understand the primary sources and characteristics of B0 distributions in the heart as well as pave the way for developing optimal B0 shim methods within heart in both subject-specific and population-based manners.

Call number: LD2668 .T4 1965 G66 / Master of Science

The multi-order response of the tuned secondary circuit of a Tesla transformer, following impulse excitation from its tuned primary circuit, is presented and analysed at the fundamental resonant frequency and at higher-order mode frequencies. A novel way of modifying the frequency response of the secondary coil is then investigated by utilising a technique normally applied to the design of a certain type of filter known as a helical filter. In general, these are used in radio and microwave frequency circuits in order to pass certain frequencies with little attenuation whilst significantly attenuating other frequencies. Design techniques, developed over several decades, modify and optimise the performance of such filters. The frequency response of the helical filter is modified by altering the geometry of the helical resonator component therein, which is typically in the form of an air-cored single-layer solenoid. A Tesla transformer whose secondary is constructed to be some form of single-layer solenoidal winding resonates at its designed frequency - its fundamental mode - but also at non-integer harmonics (higher-order anharmonic frequencies, also known as overtones). Those multi-order oscillatory voltages and currents energised in the secondary circuit have been identified and measured and research has determined the fundamental and higher-order mode frequencies and amplitudes for various experimental secondary winding configurations derived from helical filter design techniques. Applied to the Tesla transformer secondary winding, such techniques lead to a new design with a performance that is improved by the suppression of higher- order anharmonic frequencies whilst imparting little change to the fundamental response. It is anticipated that this feature will lead to Tesla transformers which exhibit enhanced spectral purity and which will be better suited to use in certain pulsed power applications than conventionally wound designs.

Background Superparamagnetic particles of iron oxide (SPIO) are part of a novel and exciting class of ‘smart’ magnetic resonance imaging (MRI) contrast agents that are taken up by inflammatory cells. Ultrasmall SPIO (USPIO; ~30 nm diameter) can be used to assess cellular tissue inflammation and SPIO (80-150 nm) have the potential to be used to label cells ex vivo for in vivo cell tracking studies. Objectives The aims of the thesis were therefore (i) to develop and validate quantitative MRI methodology for assessing SPIO uptake within tissues, (ii) to demonstrate USPIO accumulation within the aortic wall and its implications in patients with abdominal aortic aneurysms (AAA), and (iii) to develop and apply a Good Manufacturing Practice (GMP) compliant method of SPIO cell labelling in healthy volunteers. Methods Patients with asymptomatic AAA >4.0 cm in diameter were recruited. Imaging sequences were optimised in eight patients using a 3 tesla MRI scanner. Data were analysed using the decay constant for multi echo T2* weighted (T2*W) sequences (T2*) or its inverse (R2*) and the repeatability of these measurements was established. A further twenty-nine patients underwent MRI scanning before and 24- 36 hours after administration of USPIO. T2 and multi echo T2*W sequences were performed and ultrasound-based growth rate data were collected. Operative aortic wall tissue samples were obtained from patients undergoing open surgical aneurysm repair. A GMP compliant protocol was developed for labelling cells with SPIO for clinical cell tracking studies. The effects of SPIO-labelling on cell viability and function were assessed in vitro. A phased-dosing protocol was used to establish the safety of intravenous administration of SPIO-labelled cells in healthy volunteers. The feasibility of imaging cells at a target site in vivo following local or systemic administration was assessed. Tracking of SPIO-labelled cells to a target site was investigated by inducing an iatrogenic inflammatory focus in the skin of the anterior thigh of healthy volunteers, following which autologous SPIO-labelled cells were administered and their accumulation was assessed using MRI scanning and histology of skin biopsies. Results Robust and semi-quantitative data acquisition and image analysis methodology was developed for the assessment of SPIO accumulation in tissues. In patients with AAA, histological analysis of aortic wall tissue samples confirmed USPIO accumulation in areas of cellular inflammation. USPIO-enhanced MRI detected aortic wall inflammation and mural USPIO uptake was associated with a 3-fold higher aneurysm expansion rate. Human mononuclear cells were labelled with SPIO under GMP compliant conditions without affecting cell viability or function. Both local and intravenous administration of SPIO-labelled cells was safe and cells were detectable in vitro and in vivo using a clinical MRI scanner. SPIO-labelled cells tracked to a focal iatrogenic inflammatory focus following intravenous administration in humans and were detectable on MRI scanning and histological examination of skin biopsies. Conclusions SPIO contrast agents have an extensive range of potential clinical applications. USPIO uptake in the wall of AAA appears to identify cellular inflammation and predict accelerated aneurysm expansion. This is therefore a promising investigative tool for stratifying the risk of disease progression in patients with AAA, and may also be considered as a biomarker for response to novel pharmacological agents. The ability to label cells for non-invasive cell tracking studies would facilitate the further development of novel cell-based therapies and would enable assessment of dynamic inflammatory processes through inflammatory cell tracking.

Embodied Cognition accounts propose that motor activation contributes to semantic representations in action language (Fischer & Zwaan, 2008). However, the nature of this activation remains largely unspecified: in particular, which processes result in relevant activation? Long-term motor experience (e.g., the comprehender’s dominant hand), short-term motor experience (e.g., the hand the comprehender has recently used), and action planning (e.g., the hand the comprehender is planning to use) are all potential candidates. This thesis uses a range of psycholinguistic methods (e.g., timed sentence-picture matching, two-alternative forced-choice sentence-picture matching, spoken sensibility judgements) to distinguish between these possibilities. A first set of experiments investigated how comprehenders’ handedness affects their interpretation of sentences describing manual actions (e.g., I am slicing the tomato). Participants matched sentences of actions to pictures of that action. The Body-Specificity Hypothesis (Casasanto, 2009; Willems, Hagoort, & Casasanto, 2010) predicts that right-handed and left-handed comprehenders will interpret manual action sentences differently, according to whether they would perform that action with their right or their left hand. However, we found that comprehenders appear to interpret manual action sentences according to the hand they use to respond to the task, and not the hand they would typically use to perform manual actions. In addition, this effect was stronger for first-person than third-person sentences, implying that the effect of motor activation is moderated by linguistic context. A second set of experiments used the same paradigm but manipulated at what point comprehenders knew which hand they would use to respond to the sentences: during sentence processing, or after sentence processing was complete. We replicated the finding that comprehenders interpret manual action sentences according to their response hand, and that this effect was stronger for first- than for third-person sentences; but only when comprehenders knew their response hand during sentence processing. In both sets of experiments, there was no effect of whether the picture of the action was presented from an egocentric or allocentric perspective, implying that action sentences are encoded for what effector (in this case, hand) will be used in the action, but not necessarily from what perspective the action will occur. A third set of experiments investigated the existence of a causal role of action planning-based activation on sentence processing. Many studies have shown an effect of language processing on action execution (e.g., Glenberg & Kaschak, 2002; Glenberg et al., 2008), but a fully embodied theory of language also predicts an effect of motor activation on language processing. Here, right-handed participants made spoken judgements about sentences while planning an action with their right or left hand that matched or did not match the action described in the sentence. An effect of response hand on accuracy was found when the task required participants to explicitly judge the congruency of sentence and the action they were preparing, but not otherwise. These results corroborate recent research suggesting that activation of embodied lexical representations may be goal-driven rather than an automatic aspect of language processing (Hoedemaker & Gordon, 2013). Overall, the experiments presented in this thesis suggest a possible role for planning-based motor activation in sentence processing, in line with embodied approaches; however, the results challenge strong accounts of embodiment by suggesting that the effect of planning-based activation is not automatic, and is moderated by linguistic context and task demands.

Ultrasound contrast agents have the ability to provide locally increased echogenicity, improving the sensitivity and specificity of images. Due to the unique interaction of microbubbles with the imaging ultrasound field, contrast ultrasonography offers both improved diagnostic techniques, and the potential therapeutic uses of gene and drug delivery through the use of targeted agents. By enhancing the contrast at the tissue-blood interface, an improved image of the structure of organs can be achieved, which is useful in many areas of medical ultrasound imaging. Monitoring the flow of contrast agent in the blood stream also offers information on the degree of blood perfusion into an organ or microvasculature. Present knowledge of the interaction of microbubbles with ultrasound is far from complete. The full potential of contrast agents in improving diagnostic and therapeutic techniques has therefore not yet been achieved. The nonlinear and dynamic properties of microbubble response offer potentially large improvements in contrast to tissue ratio, through intelligent pulse sequence design and/or improved signal processing. Due to various drawbacks of populations studies, only by studying the response from single microbubbles can the interaction be fully understood. The variations of microbubble size and shell parameters within a typical sample of contrast agent dictate that a large number of single scatterer data are necessary to obtain information on the variability of microbubble response, which is not possible with current optical systems. This thesis aims to be a contribution to the understanding of contrast behaviour in response to medical imaging ultrasound pulses. A fully characterized microacoustic system, employing a wide-band piezoelectric transducer from a commercial ultrasound imaging system, is introduced, which enables the measurement of single scattering events. Single microbubble signals from two commercially available contrast agents, Definity R and biSphereTM, have been measured experimentally in response to a range of clinically relevant imaging parameters. The data has been analyzed, together with the results from appropriate theoretical models, in order to gain physical insight into the evolution and dynamics of microbubble signals. A theoretical model for the lipid shelled agent Definity has been developed, and the predicted response from a real sample of single microbubbles investigated. Various characteristics of resonant scatter have been identified, and used to distinguish resonant scatter in experimental acoustic single bubble data for the first time. A clear distinction between the populations of resonant and off-resonant scatter has been observed for a range of incident frequencies and acoustic pressures. Results from consecutive imaging pulses have been used to gain understanding of how initial size, shell material and encapsulated gas may effect the lifetime of a microbubble signal. The response to a basic pulse sequence is also investigated, and an alternative processing method which takes advantage of observed behaviour is presented. Improved understanding of the contrast-ultrasound interaction will provide the basis for improved signal processing tools for contrast enhanced imaging, with potential benefits to both diagnostic techniques and microbubble manufacture.

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This thesis consists of two completely separate parts. In Part I, we look at disorder in fastionic conductors, and in Part II we examine the pseudoquadrupole effect in ordered magnets. Part I looks at two aspects of the disordered state in fastionics, where the disorder is due to ions moving off their regular sites to positions close to other regular sites, a feature especially characteristic of the fluorites. The first aspect is how Coulomb interactions could be responsible for the co-operative behaviour of defects which causes the transition to fastionic behaviour. We look at this with a model of charged defects on a lattice, applying techniques involving classical diagrammatic perturbation theory to find the free energy of our model system. Using elementary thermodynamics, we show how this model can predict co-operative behaviour. The second aspect is the nature of the disorder above the fastionic transition. We look at disorder in lead fluoride using a molecular dynamics simulation with an interionic potential that we obtained. We use the simulation to examine the distribution of anions in both real space and k space. Simulations have been made on the other fluorites CaF₂ and SrCl₂ and it is possible that the high dielectric constant of lead fluoride might lead to qualitatively different behaviour. Our results show that this is not the case and we find defect concentrations similar to those obtained from CaF₂ and SrCl₂. Our Is space analysis however gives defect concentrations an order of magnitude larger, in approximate agreement with experiment. In Part II we set up a theory for the pseudoquadrupole effect in cubic ferromagnets and show that it is related to the difference in longitudinal and transverse magnetic susceptibilities. Model calculations are performed for a Heisenberg ferromagnet using molecular field theory near the critical temperature t_c, and spin wave theory at low temperatures; and the itinerant model at absolute zero and t_c. We find that the pseudoquadrupole effect in iron and nickel and at impurities in these metals appears to be very much less than measured quadrupole effects. We also look at the effect in GdAl₂ and show that it can not explain a temperature dependent quadrupole interaction seen experimentally We therefore conclude that the observed quadrupole effects are due to real electric field gradients.