Alginate is a popular biomaterial in tissue engineering. When crosslinked with calcium ions (Ca2+), alginate forms a hydrogel which provides necessary mechanical support as a scaffold. The material properties as well as the biological properties of alginate scaffold are of great importance. In this thesis, the aim is to use traditional methods, such as scanning electron microscopy (SEM) and light microscopy, and emerging X-ray imaging techniques, such as micro-computed tomography (micro-CT) and synchrotron radiation (SR) X-ray imaging, to characterize the alginate scaffolds. Firstly, the material properties of freeze-dried alginate scaffolds were evaluated using micro-CT, as it is a non-destructive and non-invasive imaging method, and can provide three-dimensional information. Alginate scaffolds made with different sodium alginate concentrations and frozen to different temperatures were scanned and analyzed in micro-CT. Results indicated that lower freezing temperature and higher sodium alginate concentration lead to smaller pore size and porosity. Secondly, cell culture experiments were carried out to study the biological properties and the interactions of alginate hydrogel with cells. A Schwann cell line was either blended with alginate solution before crosslinking with calcium chloride (CaCl2) or put around alginate gel in the culture dish. Light microscopy of sectioned slices showed that cells surrounding the alginate gel could not grow into the gel, while cells blended with alginate solution before crosslinking could proliferate inside the hydrogel. Cells grown inside a thin slice of alginate gels appeared to be in better condition and were larger in size and also grew in clusters. Thirdly, in order to image soft tissue buried inside alginate gels, such as brain slices, novel imaging methods based on synchrotron radiation (SR) were applied, such as absorption and phase contrast imaging, diffraction-enhanced imaging (DEI) and also combined with computed tomography (CT). Synchrotron-based monochromatic X-ray imaging proved to be good at distinguish objects of similar density, especially biological soft tissue samples, even without any staining material, such as osmium tetroxide (OsO4). These three pieces of research work show the potential in applying the emerging X-ray imaging in soft tissue engineering.

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.

An increasing number of fields would benefit from a single analytical probe that can characterise bulk objects that vary in morphology and/or material composition. These fields include security screening, medicine and material science. In this study the X-ray region is shown to be an effective probe for the characterisation of materials. The most prominent analytical techniques that utilise X-radiation are reviewed. The study then focuses on methods of amalgamating the three dimensional power of kinetic depth X-ray (KDFX) imaging with the materials discrimination of angular dispersive X-ray diffraction (ADXRD), thus providing KDEX with a much needed material specific counterpart. A knowledge of the sample position is essential for the correct interpretation of diffraction signatures. Two different sensor geometries (i.e. circumferential and linear) that are able to collect end interpret multiple unknown material diffraction patterns and attribute them to their respective loci within an inspection volume are investigated. The circumferential and linear detector geometries are hypothesised, simulated and then tested in an experimental setting with the later demonstrating a greater ability at discerning between mixed diffraction patterns produced by differing materials. Factors known to confound the linear diffraction method such as sample thickness and radiation energy have been explored and quantified with a possible means of mitigation being identified (i.e. via increasing the sample to detector distance). A series of diffraction patterns (following the linear diffraction appoach) were obtained from a single phantom object that was simultaneously interrogated via KDEX imaging. Areas containing diffraction signatures matched from a threat library have been highlighted in the KDEX imagery via colour encoding and match index is inferred by intensity. This union is the first example of its kind and is called diffraction enhanced KDEX imagery. Finally an additional source of information obtained from object disparity is explored as an alternative means of calculating sample loci. This offers a greater level of integration between these two complimentary techniques as object disparity could be used to reinforce the results produced by the linear diffraction geometry.

Dual-energy (DE) x-ray imaging of the chest decomposes two radiographs acquired at low- and high x-ray energies into 'soft-tissue' and 'bone' images, reducing the influence of background anatomical noise and providing increased conspicuity of subtle underlying structures compared to conventional radiography. This thesis derives a quantitative theoretical model of imaging performance in DE x-ray imaging and employs the resulting framework to system optimization in thoracic imaging. Fourier domain metrics of signal and noise performance - including the noise-power spectrum (NPS), modulation transfer function (MTF), detective quantum efficiency (DQE), and noise-equivalent quanta (NEQ) - were computed using cascaded systems analysis extended to DE imaging and combined with a quantitative model of imaging task to yield estimates of detectability across a broad range of DE image acquisition and decomposition techniques. Specifically, the detectability index provided an objective function for optimizing the selection of kVp pair, added filtration, allocation of dose between low- and high- energy views, and choice of decomposition algorithm and parameters therein. Theoretical calculations were validated in comparison to measurements of NPS, MTF, DQE, and NEQ performed on an experimental DE imaging system and through human observer studies for a variety of imaging tasks. Overall, the detectability index was found to provide a reliable predictor of human observer performance. Results identified optimal DE image acquisition and decomposition techniques that boost detectability beyond that achieved by conventional radiography or other DE imaging approaches, in many cases boosting conspicuity of subtle lesions from barely visible to highly conspicuous at fixed dose to the patient. The results are particularly encouraging, as such performance was achieved with the DE imaging dose equivalent to that of a single chest radiograph. The theoretical framework provided a valuable guide to optimization of a clinical prototype for high-performance DE chest imaging and may be extended to other DE imaging approaches, such as DE mammography and DE computed tomography.

Dual-energy (DE) x-ray imaging of the chest decomposes two radiographs acquired at low- and high x-ray energies into 'soft-tissue' and 'bone' images, reducing the influence of background anatomical noise and providing increased conspicuity of subtle underlying structures compared to conventional radiography. This thesis derives a quantitative theoretical model of imaging performance in DE x-ray imaging and employs the resulting framework to system optimization in thoracic imaging. Fourier domain metrics of signal and noise performance - including the noise-power spectrum (NPS), modulation transfer function (MTF), detective quantum efficiency (DQE), and noise-equivalent quanta (NEQ) - were computed using cascaded systems analysis extended to DE imaging and combined with a quantitative model of imaging task to yield estimates of detectability across a broad range of DE image acquisition and decomposition techniques. Specifically, the detectability index provided an objective function for optimizing the selection of kVp pair, added filtration, allocation of dose between low- and high- energy views, and choice of decomposition algorithm and parameters therein. Theoretical calculations were validated in comparison to measurements of NPS, MTF, DQE, and NEQ performed on an experimental DE imaging system and through human observer studies for a variety of imaging tasks. Overall, the detectability index was found to provide a reliable predictor of human observer performance. Results identified optimal DE image acquisition and decomposition techniques that boost detectability beyond that achieved by conventional radiography or other DE imaging approaches, in many cases boosting conspicuity of subtle lesions from barely visible to highly conspicuous at fixed dose to the patient. The results are particularly encouraging, as such performance was achieved with the DE imaging dose equivalent to that of a single chest radiograph. The theoretical framework provided a valuable guide to optimization of a clinical prototype for high-performance DE chest imaging and may be extended to other DE imaging approaches, such as DE mammography and DE computed tomography.

Small-animal x-ray imaging is an important tool for medical research. The penetration power of x-rays makes it possible to investigate the 3D structure of small animals and other thick biological samples by computed tomography (CT). However, small-animal x-ray imaging often requires high resolution due to the small structures involved, and short exposure times due to sample movement. This constitutes a challenge, since these two properties require compact x-ray sources with parameters that are not widely available. In this Thesis we present the first application of liquid-metal-jet sources for small-animal imaging. This source concept was invented at KTH just over ten years ago. The use of a high-speed metal jet as electron-beam target, instead of a solid anode, enables higher x-ray flux while maintaining a small x-ray spot for high-resolution imaging. In the present work, a liquid-metal jet source with a higher-energy spectrum has been developed. It has stronger 24 keV radiation compared to previous sources, which makes it more suitable for imaging of small animals and other few-cm-thick objects, which require the higher penetration of 20-35 keV x-rays. We have applied the liquid-metal-jet x-ray sources for whole-body imaging of sacrificed mice and zebrafish. With high-resolution absorption-contrast CT we have visualized fine bone details of mice. We have also used phase contrast, a new method that can considerably improve imaging of, e.g., soft tissue, for demarcation of mm-sized tumors inside a full mouse and for mouse cartilage imaging. In zebrafish imaging, we have exploited the greatly enhanced contrast of phase-imaging to resolve single muscle fibers (and possibly even myofibrils) in whole zebrafish in a laboratory setting for the first time. The muscle structures have diameters in the 5-7 μm range and extremely low contrast, which makes them difficult to observe. With phase contrast, we have demonstrated low-dose and high-resolution angiography of mouse and rat organs and tissues ex vivo. We show detection of blood vessels with diameters below 10 μm with radiation doses compatible with living small animals, which is not possible with absorption contrast and iodinated contrast agents. In addition, we have investigated the vascular network of tumors in mouse ears and visualized the chaotic arrangement of newly-formed blood vessels. Finally, we present the first results from a new high-power liquid-metal-jet x-ray source prototype, operating at 10× the power of our previous sources, with the same x-ray spot size. This source constitutes an important step towards future in-vivo small-animal laboratory imaging with high resolution. / Röntgenavbildning av små försöksdjur är en viktig metod inom medicinsk forskning. Röntgenstrålar penetrerar material, vilket gör det möjligt att undersöka 3D-strukturen hos försöksdjur och andra tjocka biologiska prov med hjälp av datortomografi (CT). Tyvärr kräver smådjursavbildning ofta dels hög upplösning, eftersom de relevanta strukturerna är små, dels korta exponeringstider, eftersom objektet tenderar att röra sig. Detta är en utmaning, då båda egenskaperna kräver kompakta röntgenkällor med speciella egenskaper som inte är brett tillgängliga. I denna avhandling visar vi den första användningen av metallstråleröntgenkällor för avbildning av hela smådjur. Den här typen av röntgenkälla uppfanns vid KTH för drygt tio år sedan. Genom att låta elektronerna träffa en stråle av flytande metall, istället för en solid metallanod, kan vi generera mer röntgenstrålning men samtidigt behålla en liten källpunkt, vilket behövs för avbildning med hög upplösning. En ny metallstrålekälla utvecklades som en del av denna avhandling. Den ger ett röntgenspektrum med högre energier, vilket gör källan mer lämpad än tidigare källor för avbildning av små försöksdjur och andra centimetertjocka biologiska objekt. Vi har använt metallstrålekällor för att avbilda intakta, avlivade möss och zebrafiskar. Med högupplöst absorptions-CT har vi detekterat små bendetaljer inuti möss. Vi har även använt faskontrastavbildning, en ny metod som avsevärt kan förbättra avbildning av mjukvävnad, till att demarkera millimeterstora tumörer inuti en hel mus, samt för avbildning av brosk i leder hos möss. Faskontrast ger en kraftig förstärkning av kontrasten i bilden, vilket även har använts för att för första gången detektera individuella muskelfibrer (och eventuellt även myofibriller) inuti zebrafiskar med en kompakt röntgenkälla. Muskelstrukturerna har diametrar på 5-7 μm och låg kontrast, vilket gör dem svåra att observera. Med hjälp av faskontrast har vi utvecklat en metod för att avbilda blodkärl med diametrar under 10 μm inuti organ och vävnader från möss och råttor ex vivo, med stråldoser som är kompatibla med studier av levande smådjur. Detta är inte möjligt med konventionell absorptionskontrast och jod-baserade kontrastmedel. Vi har dessutom avbildat nyformade blodkärl kring tumörer i musöron och observerat kärlens kaotiska struktur. Slutligen presenterar vi de första resultaten från en prototyp av en ny högeffektskälla. Källan har tio gånger högre effekt än tidigare metallstrålekällor, men bibehåller samma storlek på källpunkten. Den här högeffektskällan är ett viktigt steg mot framtida laboratoriebaserad avbildning av levande små försöksdjur med hög upplösning. / <p>QC 20150331</p>

An increasing number of fields would benefit from a single analytical probe that can characterise bulk objects that vary in morphology and/or material composition. These fields include security screening, medicine and material science. In this study the X-ray region is shown to be an effective probe for the characterisation of materials. The most prominent analytical techniques that utilise X-radiation are reviewed. The study then focuses on methods of amalgamating the three dimensional power of kinetic depth X-ray (KDFX) imaging with the materials discrimination of angular dispersive X-ray diffraction (ADXRD), thus providing KDEX with a much needed material specific counterpart. A knowledge of the sample position is essential for the correct interpretation of diffraction signatures. Two different sensor geometries (i.e. circumferential and linear) that are able to collect end interpret multiple unknown material diffraction patterns and attribute them to their respective loci within an inspection volume are investigated. The circumferential and linear detector geometries are hypothesised, simulated and then tested in an experimental setting with the later demonstrating a greater ability at discerning between mixed diffraction patterns produced by differing materials. Factors known to confound the linear diffraction method such as sample thickness and radiation energy have been explored and quantified with a possible means of mitigation being identified (i.e. via increasing the sample to detector distance). A series of diffraction patterns (following the linear diffraction appoach) were obtained from a single phantom object that was simultaneously interrogated via KDEX imaging. Areas containing diffraction signatures matched from a threat library have been highlighted in the KDEX imagery via colour encoding and match index is inferred by intensity. This union is the first example of its kind and is called diffraction enhanced KDEX imagery. Finally an additional source of information obtained from object disparity is explored as an alternative means of calculating sample loci. This offers a greater level of integration between these two complimentary techniques as object disparity could be used to reinforce the results produced by the linear diffraction geometry.

Abstract Research on X-ray imaging sensors and systems have been carried out for several decades. To make these X-ray scanners smaller with better performance and higher operating speed is an important subject for scientific research and industrial applications. This thesis covers a whole X-ray line-scan camera system. Special attention is given to the smart sensor micromodule design and processing technology. The smart sensor micromodule is an integrated sensor card that includes both silicon X-ray sensor array and signal-processing integrated circuits, which can perform the functions of both an optical sensor and an analog signal processor. Digital signal processing (DSP) made by application specific integrated circuits (ASICs) is also covered in this thesis. Processing technology of the photodiode array, design of the integrated circuit, design and packaging of the micromodules are presented in this thesis. The mechanism of photodiode leakage current is studied in detail. Measured results show that the leakage current level of the photodiode array achieves 80 pA/cm2 under zero bias condition, which outperforms the best photodiode reported so far. The algorithm of the digital signal processing is also studied. The X-ray scanning system can achieve 2 m/s scanning speed with a spatial resolution of 400 mm.

X-ray imaging scintillators and detectors play a critical role in numerous everyday life applications, including medical radiography, high-energy physics research, and security inspections. Despite its importance, current X-ray imaging technologies are not fully equipped to meet the growing demands for flexible, cost-efficient, and environment-friendly solutions. To overcome the limitations associated with traditional imaging scintillators, recent research efforts have focused on developing lead-free luminescent materials. Of particular interest are Cu(I) complexes, which exhibit excellent photoluminescence behavior, a facile synthesis process, and a high atomic number, making them an ideal candidate for X-ray imaging applications. Our work focuses on developing a low-dimensional Cu(I) organometallic halide and utilizing it as an imaging scintillator for real-life X-ray imaging. By utilizing the 0D Cu(I)-based imaging scintillators, we successfully obtained detailed images of both biological and non-biological objects, with a low detection limit of 458.3 nGy/s and high resolution of 16.8 lp/mm. This study not only provides a design roadmap for Cu(I) luminescent materials, but also highlights their potential for high-impact real-life X-ray imaging applications. Overall, our findings represent a significant step forward for X-ray imaging technology and its widespread applications in fields such as medicine and security.

X-ray detection methods have increasingly been used as an effective means for the automatic detection of explosives. While a number of devices are now commercially available, most of these technologies are not yet mature. The purpose of this research has been to investigate methods for using x-ray dual-energy transmission and scatter imaging technologies more effectively. Followed by an introduction and brief overview of x-ray detection technologies, a model for a prototype x-ray scanning system, which was built at Virginia Tech, is given. This model has primarily been used for the purpose of system analysis, design and simulations. Then, an algorithm is developed to correct the non-uniformity of transmission detectors in the prototype scanning system. The x-ray source output energy in the prototype scanning system is not monochromatic, resulting in two problems: spectrum overlap and output signal unbalance between high and low energy levels, which will degrade the performance of dual-energy x-ray sensing. A copper filter has been introduced and a numerical optimization method to remove thickness effect of objects has been developed to improve the system performance. The back scattering and forward scattering signals are functions of solid angles between the object and detectors. A given object may be randomly placed anywhere on the conveyor belt, resulting in a variation in the detected signals. Both an adaptive modeling technique and least squares method are used to decrease this distance effect. Finally, discriminate function methods have been studied experimentally, and classification rules have been obtained to separate explosives from other types of materials. In some laboratory tests on various scenarios by inserting six explosive simulants, we observed improvements in classification accuracy from 60% to 80%, depending on the complexity of luggage bags. / Ph. D.