The initial aim of the work presented in this thesis was to increase the soft x-ray quantum detection efficiency of a tandem-pair microchannel plate detector by the use of a CsI deposition photocathode. This aim was achieved. The coating technique and initial measurements are presented herein. After showing the use of such photocathodes, we investigated their stability and reproducibility. The effects of storage in poor vacuum, high vacuum and desiccated air are presented as is the stability of CsI photocathodes under prolonged X-ray bombardment. One consequence of the use of CsI is that a degree of energy resolution can be conferred upon a microchannel plate detector. We present further research in this field, including measurements performed on detectors with eight micron diameter channels. A feature of microchannel plate operation that is undesirable is the phenomenon of gain degradation. We performed a series of lifetests on a number of microchannel plate detectors.

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X-ray medical imaging provides invaluable medical information, while subjecting patients to hazardous ionizing radiation. The dosage that the patient is exposed to may be reduced, at the cost of image resolution. A technology that promises lower dosage for a given resolution is direct conversion digital imaging, typically based on amorphous Selenium semiconductor. Sufficient exposure should be used for the first exposure to avoid subsequent exposures; a challenge is then to reduce the necessary exposure for a suitable image. To quantify how little radiation the detector can reliably discriminate, one needs an analysis of the variance that 1/f and white noise contribute to the signal of such detectors. An important consideration is that the dark current, which varies with time, is subtracted from the photo-current, to reduce the spurious spatial variance in the image. In this thesis, the variance that 1/f noise contributes to integrating detectors is analysed, for a very general integrating detector. Experiments were performed to verify the theoretical results obtained for the 1/f noise variance contribution.

X-ray medical imaging provides invaluable medical information, while subjecting patients to hazardous ionizing radiation. The dosage that the patient is exposed to may be reduced, at the cost of image resolution. A technology that promises lower dosage for a given resolution is direct conversion digital imaging, typically based on amorphous Selenium semiconductor. Sufficient exposure should be used for the first exposure to avoid subsequent exposures; a challenge is then to reduce the necessary exposure for a suitable image. To quantify how little radiation the detector can reliably discriminate, one needs an analysis of the variance that 1/f and white noise contribute to the signal of such detectors. An important consideration is that the dark current, which varies with time, is subtracted from the photo-current, to reduce the spurious spatial variance in the image. In this thesis, the variance that 1/f noise contributes to integrating detectors is analysed, for a very general integrating detector. Experiments were performed to verify the theoretical results obtained for the 1/f noise variance contribution.

The extra energy information provided by spectral x-ray imaging using novel photon counting x-ray detectors may allow for improved decomposition of materials compared to conventional and dual-energy imaging. The information content of spectral x-ray images, however, depends on how the photons are grouped together. This thesis deals with the theoretical aspect of optimising material discrimination in spectral x-ray imaging. A novel theoretical model was developed to map the confidence region of material thicknesses to determine the uncertainties in thickness quantification. Given the thickness uncertainties, photon counts per pixel can be optimised for material quantification in the most dose efficient manner. Minimisation of the uncertainties enables the optimisation of energy bins for material discrimination. Using Monte Carlo simulations based on the BEAMnrc package, material decomposition of up to 3 materials was performed on projection images, which led to the validation of the theoretical model. With the inclusion of scattered radiation, the theoretical optima of bin border energies were accurate to within 2 keV. For the simulated photon counts, excellent agreement was achieved between the theoretical and the BEAMnrc models regarding the signal-to-noise ratio in a decomposed image, particularly for the decomposition of two materials. Finally, this thesis examined the implementation of the Medipix detector. The equalisation of pixel sensitivity variations and the processing of photon counting projection images were studied. Measurements using the Medipix detector demonstrated promising results in the charge summing and the spectroscopic modes of acquisition, even though the spectroscopic performance of the detector was relatively limited due to electronic issues known to degrade the equalisation process. To conclude, the theoretical model is sufficient in providing guidelines for scanning parameters in spectral x-ray imaging and may be applied on spectral projection measurements using e.g. the redesigned MedipixRX detector with improved spectroscopic performance, when it becomes available.

Coherent Diffractive Imaging (CDI) has become an increasingly popular frame work in which to solve the classic phase problem in imaging due to benefits in resolution and the facility of collecting data in this modality. In particular, there is considerable interest in using the short wavelength and high coherence of fourth generation x-ray sources with CDI techniques to phase non-crystalline, or nano-crystalline biomolecular samples. CDI provides an opportunity to determine the structure of proteins and other biological samples which are unable to be phased with the standard techniques of protein crystallography, typically due to lack of adequate crystalline samples. Methods of non-crystalline phase retrieval are legion, however many suffer from limitations in resolution or the inability to recover phase fields containing a pathological singularity. Wavefields containing phase singularities are common in optical fields. The creation of an x-ray wavefield containing a pathological phase singularity is demonstrated. In this thesis a form of CDI termed astigmatic diffraction is presented, that is able tophase uniquely this class of wavefield. This is achieved by illuminating the sample with beams containing known phase curvature. The theory of the method and simulations of its application to a nano-crystalline biomolecule are presented. The experimental recovery of the direction of the phase gradient of a sample illuminated with coherent x-rays produced by a synchrotron source is shown to verify this method.

Thesis (Ph.D.)--Boston University / Lutetium oxide doped with europium oxide (Lu20 3:Eu3+) has been established to be a bright, dense scintillator materi al with vast potential in both medical and high resolution X-ray imaging applications. Unfortunately its commercial viability has been restricted due to the manufacturing and post treatment costs associated with device fabrication. This research was aimed at the development of two vapor deposition techniques; chemical and physical vapor deposition (CVD and PVD), to produce coatings of Lu203:Eu3+ for various X-ray imaging applications. A customized CVD process to codeposit Lu20 3 and Eu20 3 was developed using lutetium and europium chloride (LuCb and EuCI3) precursors and reacting with carbon dioxide (C02) and hydrogen (H2) . An in depth study was performed by systematically varying the process parameters to explore the deposition kinetics and identify the rate limiting steps and their effects on the growth morphology using both cold and hot wall CVD reactors. The activation energy for the kinetically limited deposition of Lu20 3 from the LuCI3 - Ar - C02 - H2 system was identified to be approximately 170 kJ/mol , which is significantly lower than expected. The predominant growth orientations were identified to be { 111} and { 100} , depending on the deposition conditions. As the temperature is increased, the growth orientation preference decreases to produce a randomly oriented growth at 1150°C. The scintillation and X-ray imaging characteristics of a co-deposited Lu203:Eu3+ thin film with a {100} orientation were measured, confirming the feasibility and applicability of the CVD system to produce thick scintillator x-ray imaging devices. A fundamental study of the PVD process was performed by sputtering of Lu203:Eu3+ using a single target magnetron sputtering gun. Systematic vatiations of the deposition parameters were used to understand the effect of the ejected flux kinetic energies and deposition rate on the deposit density, stress, optical and scintillation properties. The deposition system was subsequently optimized for rapid, dense growth of a 10 um thick Lu203:Eu3+ coating at elevated temperatures. The X-ray imaging properties were measured and the results yielded an X-ray imaging resolution slightly better than 1 um with the potential for 0.5 um with further optimization, a level never before attained.

A new class of scintillation detector has emerged that combines columnar scintillators and CCD/CMOS sensors for high-resolution imaging. Originally developed for single-photon gamma-ray imaging, these detectors provide better than an order-of-magnitude improvement in spatial resolution compared to conventional photomultiplier tube (PMT)-based gamma cameras; sub-100 micron detector resolutions have been achieved. This work reviews the several detector configurations developed in recent years, with a specific emphasis on a type of CCD/CMOS detector developed at the Center for Gamma-Ray Imaging, which we call BazookaSPECT, that amplifies scintillation light using an image intensifier to achieve both high spatial resolution and high event-rate capability.Ongoing research into scintillator deposition techniques has led to a new form of scintillation material where crystallites are organized into columns. Similar to optical fibers, this columnar structure helps to channels scintillation light towards an exit face while restricting lateral light spread. However, because they are not perfect optical fibers, light spreads laterally and is absorbed by an amount relating to the interaction depth. Taking advantage of this phenomenon, we discuss the use of maximum-likelihood methods to estimate the 3D position and energy of gamma-ray interactions in columnar CsI(Tl)/EMCCD-based detectors.Finally, we present new imaging applications that have arisen from BazookaSPECT. These include the the development of a gamma-ray microscope using micro-coded apertures, feasibility studies for photon-counting digital mammography and eventually X-ray CT, and FastSPECT III -- a third generation small animal stationary SPECT imager. FastSPECT III system design, fabrication methods, data acquisition system, system calibration procedure, and initial tomographic reconstructions are presented.

Satellite cells are adult stem cells that contribute to hypertrophy and repair in muscles. It is hypothesized that in muscular dystrophy, the satellite cells population is depleted at a very early age, due to repeated muscle damage and repair. Satellite cell transplantation is a potentially useful therapy for muscle diseases, but the lack of an efficient delivery system has hindered its application. The presented work focuses on two specific aims that address the need for more effective cell delivery methods for cell-based therapy. In Specific Aim 1 enhanced tissue culture techniques, such as heat stress, are used to increase cell survival in satellite cell transplantation studies. Also addressed within this specific aim are methods to label and evaluate performance using real-time PCR techniques.Although much work remains to enhancing the viability of in vitro expanded myoblasts derived from satellite cells, a second important hurdle is the systemic delivery of satellite cells to multiple sites (all muscles, in the case of muscular dystrophies). In vitro and in vivo experiments are being undertaken to explore the physiological role of cell signaling systems involved in directed migration and to determine if these chemokine and growth factors can be manipulated to enhance efficacy of cell-based therapies involving skeletal muscle satellite cells. Specific Aim 2 addresses migration of satellite cells to sites of injury and methods to track transplanted cells within the host. Presented here is the use of FAST SPECT II imaging of 111-Indium oxine radiolabeled satellite cells. The long lifetime of 111-indium oxine and the ability to quantify label using FAST SPECT imaging techniques make this technique ideal for in-vivo tracking of transplanted satellite cells for week long studies. Without in-vivo imaging techniques cell fate studies require sequential animal sacrifice with histological sectioning. This not only increases the number of animals used but also adds a significant inter-animal variability to their assessment. The determination of cell fate after transplantation will have a major impact on cell therapy for treatment of muscle disease as well as other stem cell therapies.

For high-resolution X-ray imaging scintillator applications, we have prepared and optically characterized divalent samarium doped fluorochlorozirconate (FCZ:Sm2+) glasses and glass-ceramics. Sm2+ doped FCZ glasses were obtained by adding a reducing agent, NaBH4 into the initial melt to convert some of the Sm3+ to Sm2+. However, the Sm2+ concentration at most was estimated to be only approximately 0.003 %. The as-prepared glass samples were further heat treated to obtain glass-ceramics; the nucleation and growth of BaCl2 nanocrystals were confirmed by powdered X-ray diffraction (XRD) experiments. Depending on the heat treatment conditions (temperature and time), the average nanocrystal size varies from 8 to 170 nm, and the sample contains BaCl2 nanocrystals with the orthorhombic and/or hexagonal structure. The optical absorption spectra for our glass-ceramic samples suggested the substitution of Sm2+ ions into the BaCl2 lattice site. The FCZ:Sm2+ glass-ceramics samples showed strong fluorescence in the red region of spectrum (approximately 8 times that of an as-prepared glass), and the transparency can be very high (transmittance > 80 % for samples with thickness about 0.5 mm) and can be equivalent to that of an as-prepared glass . These two results promise potential as a high-resolution X-ray scintillator due to the emission wavelength range and high transparency. Extensive studies of photoluminescence (PL) spectra at low temperatures (12 -- 200 K) for FCZ:Sm2+ glass-ceramics suggested useful indicators of the crystal structure and average size of embedded BaCl2 nanocrystals. A detailed analysis of the optical spectra has lead to the identification of the origin of the emission peaks and the location of Sm ions at specific crystallographic sites. X-ray induced luminescence (XL) studies have suggested a strong dependence of the fluorescence intensity on the concentration of Sm2+ ions. In addition, for more efficient fluorescence, a sample should be heat treated in a hydrogen containing atmosphere (e.g. H2 + Ar gas), and the heat treatment conditions should be such that the nanocrystals grow in the hexagonal structure.