Dissertations / Theses on the topic 'X-ray imaging technique'

Nephrolithiasis can be a painful problem due to presence of kidney stones. Kidney stone is among the common painful disorders of the urinary system. Various imaging modalities are used to diagnose patients with symptoms of renal or urinary tract disease such as plain kidney, ureter, bladder x-ray (KUB), intravenous pyelography (IVP), and computed tomography (CT). As a traditional three-dimensional (3D) nephrolithiasis and kidney stones detection technique, computed tomography (CT) provides detailed cross-sectional images as well as 3D structure of kidney from moving the x-ray beam in a circle around the body. However, the risk of CT scans of the kidney is relatively higher exposure to radiation which is more than regular x-rays. C-arm technique is a new x-ray imaging modality that uses 2D array detector and cone shaped x-ray beam to create 3D information about the scanned object. Both x-ray source and 2D array detector cells mounted on C-shaped wheeled structure (C-arm). A series of projection images are acquired by rotating the C-arm around the patient in along circular path with a single rotation. The characteristic structure of C-arm allows to provide wide variety of movements around the patient that helps to remain the patient stationary during scanning time. In this work, we investigated a C-arm technique to generate a series of tomographic images for nephrolithiasis and detection of kidney stones. C-arm tomographic technique (C-arm tomosynthesis) as a new three dimensional (3D) kidney imaging method that provides a series of two dimensional (2D) images along partial circular orbit over limited view angle. Our experiments were done with kidney phantom which formed from a pig kidney with two embedded kidney stones inside it and low radiation dosage. Radiation dose and scanning time needed for kidney imaging are all dramatically reduced due to the cone beam geometry and also to limitation of angular rotation. To demonstrate the capability of our C-arm tomosynthesis to generate 3D kidney information for kidney stone detection, two groups of tomographic image reconstruction algorithms were developed for C-arm tomosynthesis: direct algorithms such as filtered back projection (FBP) and iterative algorithms such as simultaneous algebraic reconstruction technique (SART), maximum likelihood expectation maximization (MLEM), ordered- subset maximum likelihood expectation maximization (OS-MLEM) and Pre-computed penalized likelihood reconstruction (PPL). Three reconstruction methods were investigated including: pixel-driven method (PDM), ray-driven method (RDM) and distance driven method (DDM). Each method differs in their efficiency of calculation accuracy per computing time. Preliminary results demonstrated the capability of proposed technique to generate volumetric data about the kidney for nephrolithiasis and kidney stone detection by using all investigated reconstruction algorithms. In spite of each algorithms differs in their strategies, embedded kidney stone can be clearly visualized in all reconstruction results. Computer simulation studies were also done on simulated phantom to evaluate the results for each reconstruction algorithm. To mimic kidney phantom, simulated phantom was simulated with two different size kidney stones. Dataset of projection images was collated by using a virtual C-arm tomosynthesis with geometric configuration similar to real technique. All investigated algorithms were used to reconstruct 3D information. Different of image quality functions were applied to evaluate the imaging system and the reconstruction algorithms. The results show the capability of C-arm tomosynthesis to generate 3D information of kidney structures and to identify the size and location of kidney stones with limited amount of radiation dose.

Over the past couple of decades there has been tremendous advancements in the field of medicine and engineering technology. Increases in the level of integration between these two branches of science has led to better understanding of physiology and anatomy of a living organism, thus allowing for better understanding of diseases along with their cures and treatments. The work presented in this dissertation aims at improving the imaging aspects of x-ray image guided interventions with endovascular image guided intervention as the primary area of application.

Minimally invasive treatments for neurovascular conditions such as aneurysms, stenosis, etc involve guidance of catheters to the treatment area, and deployment of treatment devices such as stents, coils, balloons, etc, all under x-ray image guidance. The features in these device are in the order of a few 10 µm's to a few 100 µm's and hence demand higher resolution imaging than the current state of the art flat panel detector. To address this issue three high resolution x-ray cameras were developed. The Micro Angiography Fluoroscope (MAF) based on a Charge Coupled Device (MAF-CCD), the MAF based on Complementary Metal Oxide Semiconductors (MAF-CMOS) and the Solid State X-ray Image Intensifier based on Electron Multiplying CCDs. The construction details along with performance evaluations are presented. The MAF-CCD was successfully used in a few interventions on human patient to treat neurovascular conditions, primarily aneurysm. Images acquired by the MAF-CCD during these procedures are presented.

A software platform CAPIDS was previously developed to facilitate the use of the high resolution MAF-CCD in a clinical environment. In this work the platform was modified to be used with any camera. The upgrades to CAPIDS, along with parallel programming including both the Graphics Processing Unit (GPU) and Central Processing Unit (CPU) are presented.

With increasing use of x-ray guidance for minimally invasive interventions, a major cause of concern is that of prolonged exposure to x-ray radiation that can cause biological damage to the patient. Hence during x-ray guided procedures necessary steps must be taken to minimize the dose to the patient. In this work a novel dose reduction technique, using a combination of Region of Interest (ROI) fluoroscopy to reduce dose along with spatially different temporal filtering to restore image quality is presented.

Finally a novel ROI imaging technique for biplane imaging in interventional suites, combining the use of high resolution detector along with dose reduction technique using ROI fluoroscopy with spatially different temporal filtering is presented.

For the education of X-ray imaging, having a detailed knowledge on the interaction of radiation with matter is very important. Also the generation and detection concepts of the X-ray have to be grasped well. Sometimes it is not easy to visualize the interactions and assess the scheme in quantum physics level for the medical doctors and the engineers who have not studied on the modern physics in an appropriate level. This thesis aims to visualize these interactions, X-ray generation and detection, and computerized tomographic imaging. With these simulations, the user can 1) observe and analyze which type of interaction occurs under which condition, 2) understand the interaction cross sections and interaction results, 3) visualise X-ray generation and detection features, 4) clarify the method of image reconstruction, and the features affecting the image quality in computerized tomography system. This is accomplished by changing the controllable variables of the radiation and the systems with the provided interfaces. In this thesis, JAVA/FLASH based simulation interfaces are designed to easily assess the subject. The benefits of these software are their ability to execute the programs prepared on the World Wide Web media. The interfaces are accessible from anywhere, at any time.

X-ray micro computed tomography (Micro-CT) has emerged as a powerful tool in petroleum industry for non-destructive 3D imaging of rock samples, that offers micron-scale spatial resolution images of the distribution of porosity, permeability, and fluid phases of the specimens. Micro-CT obtain the radiographic projections of a sample at different angles and use a mathematical procedure to reconstruct a 3D tomogram of the sample's X-ray attenuation coefficients. Through my thesis, the aim was to investigate and improve two main issue which micro-CT suffers from: 1) beam hardening (BH) artefacts and, 2) the requirement of material characterisation. This thesis contributes in addressing these fundamental issues by providing the "energy selective techniques" as follows. Chapter 1 provides an overview of the basics of tomography including physics of X-rays and energy dependent form of attenuation coefficient. Chapter 2 reviews the BH effects and the existing correction methods, followed by a brief review of the material characterisation methods. Chapter 3 assess the accuracy of five different linearisation BH correction models including polynomial, bimodal, power law, cubic spline and zero-order using the sample that have been imaged at ANU CT facility by measuring the BH curves directly and remapping the inverse of the models to data. Chapter 4 is based on a published conference proceeding paper [1] that applies the power law BH correction method of chapter 3 to correct the artefacts of specimens composed of concentric cylinders, e.g., a rock core within a container. Chapter 5 is based on a published paper in the Journal of Applied Physics [2] that uses dual-energy CT and the Alvarez and Macovski [3] transmitted intensity (AMTI) model to estimate the maps of density (rho) and atomic number (Z) of mineralogical samples. In this method, the attenuation coefficients are represented in the form of the two most important interactions of X-rays with atoms that is, PE and CS. This enables material discrimination as PE and CS are respectively dependent on Z and rho of materials [3]. Chapter 6 implements two simplified form of the full model of chapter 5: 1) Alvarez and Macovski polynomial (AMP) model [3], Alvarez and Macovski presented the full model but used a polynomial simplified form of it to estimate rho and Z of materials, 2) Siddiqui and Khamees (SK) model [4] that simplified the attenuation model, by assuming two monochromatic radiations. Chapter 7 presents a method to estimate the properties of sample materials from measurements of transmitted intensity and its statistical variance (TIV model). The method only requires single energy imaging, i.e., eliminates the need for requirements of dual-energy imaging for AMTI method and its simplified forms. The registered intensity on the detector is proportional to a form of "average" energy of detected quanta of X-ray spectra. The variance images can serve the same purpose as the higher energy information required in dual-energy imaging. Chapter 8 modified the TIV model of chapter 7 to apply it directly for BH correction without necessarily estimation of the properties of sample materials. The chapter also presents a simplified form of TIV model (STIV) that normalises the average intensity image.

This dissertation presents the characterization and evaluation of a new radiological imaging modality, Toshiba Computed Radiography (TCR) 201. The characteristics of the TCR storage phosphor imaging plates such as energy-dependent x-ray quantum efficiency, stored signal decay, low exposure rate signal build-up, and spontaneous and stimulated gain measures are presented. The TCR 201 system is characterized by the signal transfer curve, the total root-mean-squared (rms) output noise, the signal-to-noise ratio, the modulation transfer function (MTF), its noise power spectrum (NPS), and the detective quantum efficiency (DQE). The system rms noise is photon-limited for exposures less than 1.0 mR, but has contributions from phosphor structure and quantization noise for exposures higher than 1.0 mR. The phosphor's information factor is shown to explain deviations from ideal photon-limited noise for exposures of less than 1.0 mR. The MTF of the system is measured for standard imaging plates, 10% at 2.8 lp/mm, and for high resolution imaging plates, 10% at 4.4 lp/mm. An expression for the NPS is statistically derived, and experimental measurements confirm the expression and show an increase in uncorrelated noise power above 1.0 mR which is consistent with rms measurements. Expressions for the DQE are presented. A psychophysical study is performed to directly compare the TCR to film/screen combinations in imaging low-contrast objects. The results of this study show the TCR provides better images for detectability as a function of exposure. Also, the use of the TCR 201 as a two dimensional dosimeter and in single-shot dual energy subtraction is presented.

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2008.
Includes bibliographical references (p. 50).
Improvised explosive devices (IED) pose a very serious threat to civilians and military forces around the world, and new technologies must be developed for the early detection of these objects. Because of the high concentrations of low atomic number material such as nitrogen and hydrogen present in these explosives, x-ray backscattering provides a viable method of collecting information about these targets by analyzing their shape. Furthermore, a coded aperture used in conjunction with dynamic reconstruction algorithms offers high sensitivity and resolution even while the target is moving towards the detector. This paper describes a lab-based system that simulated a source-target-detector arrangement to be utilized in a radiation detecting vehicle in order to test dynamic reconstruction methods. Using a 225 kVp x-ray tube as the source, a medical CT-system camera fitted with a drill mask of 50% fill factor as the detector, and both radioisotope sources and low Z backscatter targets, images were acquired and reconstructed. The geometry of the experimental setup was optimized to reduce background noise from air scatter and environmental sources, as well as to prevent incident photons from directly reaching the detector from the x-ray tube. Measurements of a Co-60 point source and Co-57 area source with high activity generated high contrast images for which the shapes of the sources were clearly resolved. Acquisitions with varying target-detector distance of low Z materials, including a filled water jug and a four inch thick polyethylene arrow, produced lower contrast images in which the shapes were not as easily distinguished. The radioisotope tests were a proof of principle for dynamic reconstruction and the backscatter targets provided much insight on methods for improving the lab system, including the addition of steel behind the target, the narrowing of the detector energy window, and reassessment of the x-ray cone-beam.
by Tiffany Lee.
S.B.

The primary aim of the work presented in this thesis is to elucidate novel information regarding the uptake, storage, distributions, and functions of both copper and zinc in mammalian cells by predominantly using a combination of the high resolution imaging modalities, synchrotron radiation X-ray fluorescence microscopy (SXRF) and standard fluorescence imaging. Results from studies using cell permeable, metal ion selective fluorescent probes suggested the presence of labile pools of copper and zinc localized within the mitochondria and Golgi apparatus. Furthermore, SXRF imaging of a cell line defective in the copper transporter, Atox1, revealed intriguing differences in the Cu distribution of Atox1-/- cells compared to the corresponding wild-type cells. Finally, spatially well-resolved SXRF elemental maps of single, adherent mouse cells revealed remarkable changes in the distributions of both zinc and copper as the cells progressed through the cell cycle. Taken together, findings suggested major roles for copper and zinc within a native biological setting.

Thesis (MSc)--Stellenbosch University, 2000.
ENGLISH ABSTRACT: A digital portal X-ray imaging system was developed to replace the radiographic X-ray films currently used for patient position verification at the National Accelerator Centre (NAC) proton therapy facility. The main advantage of a digital system is the short time in which the image can be obtained. Other advantages include optimisation of the image display, effective archiving of the digital images, access from various locations through data networks, and lower operational costs. The digital system described in this thesis consists of a Gd202S:Tb scintillator screen for converting X-rays to visible light, a protected aluminum front silvered mirror to direct the light to a Charge Coupled Device (CCD) camera for capture and a personal computer for data acquisition, processing and display. Compared with other digital imaging systems, this is a simple, compact and affordable system. The properties of the various components were investigated. The Rarex G-130 (Gd202S:Tb) scintillation screen was chosen for its good spatial resolution, high emission efficiency and good matching between the spectral emission wavelength peak and the quantum efficiency of the CCD camera. The spatial resolution measured for the system with a field of view (FOV) of 290 x 190 mnr' is 1.3 lp/mm, which can be improved by increasing the CCD chip resolution or decreasing the field of view, since the CCD camera limits the spatial resolution. Intrinsic detector noise determines the lower limit of the dynamic range of the detector and is reduced by cooling the CCD camera. A dark current exposure is subtracted from the image to remove the bias signal and background signal level mainly caused by thermal noise. Photon noise, beam in-homogeneity and efficiency variations across the CCD chip are removed by a flat field correction. The digital images obtained with this system compare very well with the currently used radiographic film images and they are satisfactory for the purpose of patient position verification. Using the digital system it is possible to reduce the patient dose by 19 % and still obtain satisfactory image quality.
AFRIKAANSE OPSOMMING: 'n Digitale X-straalafbeeldingstelsel is ontwikkel om die radiografiese X-straalfilm wat tans gebruik word vir die kontrolering van die pasientposisionering voor die toediening van protonterapie by die Nasionale Versnellersentrum, te vervang. Die voordeel van die digitale sisteem is dat die beelde feitlik onmiddellik beskikbaar is. Verdere voordele sluit die optimisering van die vertoon van beeldkontras, effektiewe liassering, vinnige bereik deur datanetwerke en lae lopende kostes in. Die digitale sisteem beskryf in die tesis bestaan uit 'n gadolinium oksi-sulfied (Gd202S:Tb) sintillasieskerm wat X-strale omskakel na sigbare lig, 'n eerste-oppervlak aluminiumspieël wat die lig na 'n digitale kamera (CCD kamera) weerkaats en In persoonlike rekenaar vir dataverwerwing, verwerking en vertoon. Vergeleke met ander digitale stelsels is hierdie digitale beeldingstelsel eenvoudig, kompak en bekostigbaar. Die eienskappe van die verskillende komponente van die stelsel is ondersoek. Die Rarex G- 130 (Gd202S:Tb) sintillasieskerm IS gekies vanweë goeie resolusie, hoë emissiedoeltreffendheid en die hoë omsettingsdoeltreffendheid van die digitale kamera by die spektrale emissiegolflengte van dié sintillasieskerm. Die ruimtelike oplosvermoë van die stelsel is bepaal met In veldgrootte van 290 x 190 mnr' as 1.3 lynpare per millimeter. Die ruimtelike oplosvermoë kan verhoog word deur die kameraresolusie te verhoog of die veldgrootte te verklein, omdat die resolusie van die kamera tans die oplosvermoë van die stelsel beperk. Intrinsieke ruis van die detektor beperk die onderste grens van die dinamiese reikwydte van die detektor en kan verminder word deur die kamera te verkoel. 'n Donkerstroom-beeld word van die X-straalbeelde afgetrek om die voorspanningsein en die agtergrondsein, wat hoofsaaklik veroorsaak word deur termiese ruis, te verwyder. Ruis wat ontstaan as gevolg van fluktuasies in die aantal fotone, nie-homogeniteite in die bundel of variasie van die sensitiwiteit in die skerm word verwyder met behulp van 'n plat vlak beeld. Die digitale beelde verkry met die stelsel vergelyk goed met die beelde wat tans op film geneem word en die beeldkwalitiet is voldoende vir die kontrolering van die pasientopstelling. Dit is moontlik om die pasiëntdosis met 19 % te verminder en steeds voldoende beeldkwaliteit te verkry.

The ongoing development of storage devices and technologies for medical image management has led to a growth in the digital archiving of these images. The characteristics of medical x-rays are examined, and a number of digital coding methods are considered. An investigation of several fast cosine transform algorithms is carried out. An adaptive cosine transform coding technique is implemented which produces good quality images using bit rates lower than 0.38 bits per picture element

We envisage a fundamental study of the physical mechanisms (dislocation slip versus deformation twinning) involved in plastic deformation of hexagonal close-packed (HCP) metals like titanium and magnesium. A novel combination of X-ray imaging and diffraction techniques, termed X-ray diffraction contrast tomography (DCT), will be used to investigate details of the deformation process in the bulk of polycrystalline specimen. DCT provides access to the position, 3D shape, (average) orientation and elastic strain tensor of grains in polycrystalline sample volumes containing up to 1000 grains and more. Ultimately, an extension of the X-ray DCT technique is associated with a section topography methodology on the same instrument. This combination enables the measurement of local orientation and elastic strain tensors inside selected bulk grains. A very preliminary study of this approach is carried out on a magnesium alloy, underlying the current limitations and possible improvements of such approach. In this thesis, the data acquisition and analysis procedures required for this type of combined characterisation approach have been developed. The work is supported by the use of neutron diffraction, for an in-situ loading experiments, and two-dimensional electron backscatter diffraction (EBSD), for the initial microstructure of the materials and cross-validation of the results obtained with the X-ray DCT technique.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, February 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Phase Contrast Imaging (PCI) was studied with the goal of understanding its relevance and its requirements. Current literature does not provide insight on the effect of a relaxation in coherence requirements on the PCI capabilities of an imaging system. This problem is all the more important since coherent X-ray and Neutron sources are mostly unavailable. We develop a model for PCI contribution to imaging for partially incoherent systems, and develop a methodology to identify a minimum and an optimum coherence length 4min and opt. We propose a figure-of-merit KPcI that quantifies the PCI capabilities of an imaging system. Our calculations show that X-ray PCI systems based on free space propagation using microfocus X-ray tubes have little PCI capabilities. We develop a model to explain the edge enhancement observed with those systems; our results suggest that scatter reduction is the process responsible for the observed edge enhancement. We performed experiments that show good agreement with the model. Coded Source Imaging (CSI) is proposed as a tool to produce highly coherent sources. The general theory of CSI is developed. We propose two possible systems: Fluorescent Coded Sources (FCS) and the AEB Encoded X-ray tube.
by Antonio Leonardo Damato.
Ph.D.

Multispectral imaging (MSI) used as Initial studies to identify and study painted layers as a non-destructive method. The use of MSI to tentatively identify pigments has an important advantage justifying its application the rapid and low-cost survey of large areas.it is possible to tentatively identify some historical pigments and discover the invisible layers, painting and writing. By means of MSI performed with simplified equipment and without the aid of imaging analysis software. The two selected objects from the Grand Egyptian Museum collection were rich in pigments, first object is polychrome anthropoid wooden coffin lid (GEM No. 22452) the date back to 21st Dynasty (c. 1070 - 945 B.c.) Late period, which belong to the collection of Bab el- Gusus tomb and the second is a Cartonnage mummy trappings on linen (GEM No. 8615) date back to27th dynasty, late period. Different imaging techniques of multispectral imaging like ultraviolet methods (UVF, UVR, and UVRFC) and Infrared methods (IRF, IR, IRFC and IRT) will be studied and evaluated regarding to the efficiency and effectively. Mixing between multispectral imaging and Reflectance transformation imaging will be applied and tested by mix and match between these two techniques we can add value for the results we can get. Several methods will be applied practically to have the required results for evaluating these methods. X-ray fluorescence (XRF) spectrometry was used as a complementary analysis for the identification of the pigments.

Natural stones have been widely used in the construction field since antiquity. Building materials undergo decay processes due to mechanical,chemical, physical and biological causes that can act together. Therefore an interdisciplinary approach is required in order to understand the interaction between the stone and the surrounding environment. Utilization of buildings, inadequate restoration activities and in general anthropogenic weathering factors may contribute to this degradation process. For this reasons, in the last few decades new technologies and techniques have been developed and introduced in the restoration field. Consolidants are largely used in restoration and conservation of cultural heritage in order to improve the internal cohesion and to reduce the weathering rate of building materials. It is important to define the penetration depth of a consolidant for determining its efficacy. Impregnation mainly depends on the microstructure of the stone (i.e. porosity) and on the properties of the product itself. Throughout this study, tetraethoxysilane (TEOS) applied on globigerina limestone samples has been chosen as object of investigation. After hydrolysis and condensation, TEOS deposits silica gel inside the pores, improving the cohesion of the grains. X-ray computed tomography has been used to characterize the internal structure of the limestone samples,treated and untreated with a TEOS-based consolidant. The aim of this work is to investigate the penetration depth and the distribution of the TEOS inside the porosity, using both traditional approaches and advanced X-ray tomographic techniques, the latter allowing the internal visualization in three dimensions of the materials. Fluid transport properties and porosity have been studied both at macroscopic scale, by means of capillary uptake tests and radiography, and at microscopic scale,investigated with X-ray Tomographic Microscopy (XTM). This allows identifying changes in the porosity, by comparison of the images before and after the treatment, and locating the consolidant inside the stone. Tests were initially run at University of Bologna, where characterization of the stone was carried out. Then the research continued in Switzerland: X-ray tomography and radiography were performed at Empa, Swiss Federal Laboratories for Materials Science and Technology, while XTM measurements with synchrotron radiation were run at Paul Scherrer Institute in Villigen.

The advent of highly-coherent x-ray light sources, such as those now available world-wide in modern third-generation synchrotrons and increasingly available in free-electron lasers, is driving the need for improved analytical and experimental techniques which exploit the coherency of the generated light. As the light illuminating a sample approaches full coherence, a simple Fourier transform describes the diffraction pattern generated by the scattered light in the far field; because the Fourier transform of an object is unique, coherent scattering can directly probe local structure in the scattering object instead of bulk properties. In this dissertation, we exploit the coherence of Advanced Light Source beamline 12.0.2 to build three types of novel coherent scattering microscopes. First, we extend the techniques of coherent diffractive imaging and Fourier transform holography, which uses iterative computational methods to invert oversampled coherent speckle patterns, into reflection geometry. This proof-of-principle experiment demonstrates a method by which reflection Bragg peaks, such as those from the orbitally-ordered phase of complex metal oxides, might eventually be imaged. Second, we apply a similar imaging method to the x-ray beam itself to directly image the mutual coherence function with only a single diffraction pattern. This technique supersedes the double-slit experiments commonly seen in the scattering literature to measure the mutual intensity function by using a set of apertures which effectively contains all possible double slit geometries. Third, we show how to evaluate the speckle patterns taken from a labyrinthine domain pattern for "hidden" rotational symmetries. For this measurement, we modify the iterative algorithms used to invert speckle patterns to generate a large number of domain configurations with the same incoherent scattering profile as the candidate pattern and then use these simulations as the basis for a statistical inference of the degree of ordering in the domain configuration. We propose extending this measurement to position-resolved speckle patterns, creating a symmetry-sensitive microscope. The three new techniques described herein may be employed at current and future light sources.

Physics
Ph.D.
In this dissertation, we have used a combination of synchrotron-based x-ray spectroscopic, scattering and imaging techniques to investigate the electronic, magnetic and structural properties of materials and material systems which exhibit natural as well as engineered nanoscale structural distortions. In order to investigate the interplay between the above-mentioned degrees of freedom with spatial and depth resolution, we have utilized non-destructive techniques, such as x-ray absorption spectroscopy (XAS), polarization-dependent photoemission electron microscopy (PEEM), nanoscale scanning x-ray diffraction microscopy (nano-SXDM) and standing-wave x-ray photoemission spectroscopy (SW-XPS). The results were compared to several types of state-of-the-art first-principles theoretical calculations. In the first part of the dissertation, we have investigated the nanoscale magneto-elastic structure of the Fe3Ga magnetic alloy, which was recently reported to exhibit non-volume conserving magnetostriction. As the result of our combined PEEM and nano-SXDM study, we have discovered the structural basis for this phenomenon – periodic long-wavelength (~269 nm) elastic domain walls, with domains (regions of zero-strain) existing as narrow transition regions. Atto-scale elastic gradients and self-strain across the elastic domain walls were quantitatively measured and imaged by nano-SXDM. Our measurements revealed that the gradients inside the elastic walls are accommodated by gradually increasing/decreasing inter-planar spacing resembling a longitudinal wave. Our element-specific polarization-dependent PEEM measurements revealed that the magnetic structure of the crystal modulates with similar periodicity (~255 nm), and the resulting magneto-elastic coupling produces a ‘giant’ field-induced bulk deformation, which is equal to the measured self-strain of the elastic domain wall. In the second part of this dissertation, we utilized a combination of soft x-ray standing-wave photoemission spectroscopy (SW-XPS), hard x-ray photoemission spectroscopy (HAXPES) and scanning transmission electron microscopy (STEM) to probe the depth-dependent and single-unit-cell resolved electronic structure of isovalent manganite superlattices (Eu0.7Sr0.3MnO3/La0.7Sr0.3MnO3)15 wherein the electronic and magnetic properties are intentionally modulated with depth via engineered O octahedral rotations and A-site displacements. Standing-wave-excited spectroscopy of the Mn 2p and O 1s core-levels confirmed the isovalent nature of the Mn ions in the superlattice and revealed significant depth-dependent variations in the local chemical and electronic environment around the O atoms, consistent with the state-of-the-art theoretical calculations. Furthermore, it was shown that a surface relaxation and orbital reconstruction in the several top Eu0.7Sr0.3MnO3 atomic layers produces substantial changes in the observed electronic structure, which, according to the first-principles theoretical calculations, occur due to the establishment of orbital stripe order in the top unit cell. In summary, we have used synchrotron-based x-ray spectroscopic and microscopic techniques, in conjunction with high-resolution electron microscopy, to study the electronic, magnetic and structural properties of advanced functional materials exhibiting strong nanoscale heterogeneity. We discovered a strong coupling between the nanoscale structural and magnetic properties in the non-conventional magnetostrictive Fe3Ga single crystal. Our results suggest that this coupling provides the fundamental basis for the non-conventional magnetostriction phenomenon in this material. We have also discovered that the electronic properties of the Eu0.7Sr0.3MnO3/La0.7Sr0.3MnO3 superlattices can be epitaxially tuned via engineered A-site cation displacement, which is a result of the strong interfacial coupling between the Eu0.7Sr0.3MnO3 and La0.7Sr0.3MnO3 layers. This suggests a new way of tailoring and spatially-confining electronic and ferroic behavior in complex oxide heterostructures and creating novel ordered surface-reconstruction effects.
Temple University--Theses

The advent of highly-coherent x-ray light sources, such as those now available world-wide in modern third-generation synchrotrons and increasingly available in free-electron lasers, is driving the need for improved analytical and experimental techniques which exploit the coherency of the generated light. As the light illuminating a sample approaches full coherence, a simple Fourier transform describes the diffraction pattern generated by the scattered light in the far field; because the Fourier transform of an object is unique, coherent scattering can directly probe local structure in the scattering object instead of bulk properties.

In this dissertation, we exploit the coherence of Advanced Light Source beamline 12.0.2 to build three types of novel coherent scattering microscopes. First, we extend the techniques of coherent diffractive imaging and Fourier transform holography, which uses iterative computational methods to invert oversampled coherent speckle patterns, into reflection geometry. This proof-of-principle experiment demonstrates a method by which reflection Bragg peaks, such as those from the orbitally-ordered phase of complex metal oxides, might eventually be imaged. Second, we apply a similar imaging method to the x-ray beam itself to directly image the mutual coherence function with only a single diffraction pattern.

This technique supersedes the double-slit experiments commonly seen in the scattering literature to measure the mutual intensity function by using a set of apertures which effectively contains all possible double slit geometries. Third, we show how to evaluate the speckle patterns taken from a labyrinthine domain pattern for "hidden" rotational symmetries. For this measurement, we modify the iterative algorithms used to invert speckle patterns to generate a large number of domain configurations with the same incoherent scattering profile as the candidate pattern and then use these simulations as the basis for a statistical inference of the degree of ordering in the domain configuration. We propose extending this measurement to position-resolved speckle patterns, creating a symmetry-sensitive microscope. The three new techniques described herein may be employed at current and future light sources.

The combination of X-ray imaging and diffraction techniques provides a unique tool for structural and mechanical analysis of engineering components. A variety of modes can be employed in terms of the spatial resolution (length-scale), time resolution (frequency), and the nature of the physical quantity being interrogated. This thesis describes my contributions towards the development of novel X-ray “rich” imaging experimental techniques and data interpretation. The experimental findings have been validated via comparison with other experimental methods and numerical modelling. The combination of fast acquisition rate and high penetration properties of X-ray beams allows the collection of high-resolution 3-D tomographic data sets at submicron resolution during in situ deformation experiments. Digital Volume Correlation analysis tools developed in this study help understand crack propagation mechanisms in quasi-brittle materials and elasto-plastic deformation in co-sprayed composites. For the cases of crystalline specimens where the knowledge of “live” or residual elastic strain distributions is required, diffraction techniques have been advanced. Diffraction Strain Tomography (DST) allows non-destructive reconstruction of the 2-D (in-plane) variation of the out-of-plane strain component. Another diffraction modality dubbed Laue Orientation Tomography (LOT), a grain mapping approach has been proposed and developed based on the translate-rotate tomographic acquisition strategy. It allows the reconstruction of grain shape and orientation within polycrystalline samples, and provides information about intragranular lattice strain and distortion. The implications of this method have been thoroughly investigated. State-of-the-art engineering characterisation techniques evolve towards scrutinising submicron scale structural features and strain variation using the complementarity of X-ray imaging and diffraction. The first successful feasibility study is reported of in operando stress analysis in an internal combustion engine. Finally, further advancement of ‘rich’ imaging techniques is illustrated via the first successful application of Time-of-Flight Neutron Diffraction Strain (TOF-NDST) tomography for non-destructive reconstruction of the complete strain tensor using an inverse eigenstrain formulation.

Cancer is one of the leading causes of death worldwide, and affects roughly 1.5 million new people in the United States every year. One of the leading tools in the detection and treatment of cancer is radiation. Tumors can be detected and identified using CT or PET scans, and can then be treated with external beam radiotherapy or brachytherapy. By taking advantage of the physical properties of gold and the biological properties of nanoparticles, gold nanoparticles (GNPs) can be used to improve both cancer radiotherapy and imaging. By infusing a tumor with GNPs, either using passive extravasation of nanoparticles by the tumor vasculature or active targeting of an antibody-conjugated nanoparticle to a specific tumor marker, the higher photon cross-section of gold will cause more radiation dose to be deposited in the tumor during photon-based radiotherapy. In principle, this would allow escalation of dose to the tumor while not increasing the dose to normal healthy tissue. Additionally, if a tumor infused with GNPs was irradiated by an external kilo-voltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration. This work has two main aims: to quantify the GNP-mediated dose enhancement during GNRT on a nanometer scale, and to develop a refined imaging modality capable of quantifying GNP location and concentration within a small-animal-sized object. In order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model was developed. This model combines both large-scale and small-scale calculations in order to accurately determine the heterogeneous dose distribution of GNPs. The secondary electron spectra were calculated using condensed history Monte Carlo, which is able to accurately take into account changes in beam quality throughout the tumor and calculate the average energy spectrum of the secondary charged particles created. Then, the dose distributions of these electron spectra were calculated on a nanometer scale using event-by-event Monte Carlo. The second aim is to develop an imaging system capable of reconstructing a tomographic image of GNP location and concentration in a small animal-sized object by capturing gold fluorescence photons emitted during irradiation of the object by an external beam. This would not only allow for localization of GNPs during gold nanoparticle-aided radiation therapy (GNRT), but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies. The purpose of this study is to develop a cone-beam implementation of XFCT that meets realistic constrains on image resolution, detection limit, scan time, and dose. A Monte Carlo model of this imaging geometry was developed and used to test the methods of data acquisition and image reconstruction. The results of this study were then used to drive the production of a functioning benchtop, polychromatic cone-beam XFCT system.

L’imagerie plénoptique est une technique basée sur l’acquisition des informations spatiales et angulaires des rayons lumineux provenant d’une scène. A partir d’une seule acquisition, un traitement numérique des données permet diverses applications comme la synthèse d’ouverture, le changement de point de vue, la refocalisation à différentes profondeurs, voire une reconstruction en 3D de la scène. L’imagerie plénoptique est beaucoup étudiée dans le visible. La transposition du visible dans le domaine des rayons X est un réel défi. L’imagerie plénoptique permettrait une imagerie 3D en rayons X à partir d’une seule acquisition. Cela aiderait à réduire fortement la dose absorbée par l’échantillon, par rapport à la tomographie qui nécessite une centaine de vues.Dans cette thèse, nous considérons une caméra plénoptique constituée d’une lentille principale, d’une matrice de microlentilles et d’un détecteur. Deux configurations optiques distinctes, constituées de ces trois éléments, sont présentées dans la littérature : la caméra plénoptique « traditionnelle » et celle « focalisée ». La principale différence se trouve dans les distances entre les éléments optiques. L’observation d’une continuité entre ces deux configurations nous a amené à établir un système unique d’équations permettant leur conception optique, ainsi que l’expression théorique des résolutions associées. Ces résolutions ont été validées expérimentalement dans le visible. De plus, l’étude de l’évolution du contraste en fonction de la profondeur a montré que le contraste diminue quand on s’éloigne d’une position privilégiée intrinsèque à la configuration. C’est un résultat important car il pourrait affecter la qualité de l’image reconstruite et l’extraction de la profondeur.Nous avons aussi travaillé sur les algorithmes de refocalisation préexistants, développés indépendamment pour chaque configuration. Nous avons élaboré un nouvel algorithme valide pour les deux configurations. Ce dernier est basé sur les distances physiques entre les éléments optiques, et permet une refocalisation à une distance arbitraire de la caméra. Tout d’abord, nous avons défini une nouvelle paramétrisation entre les espaces objet et image, en établissant la relation matricielle qui régit le trajet d’un rayon lumineux à l’intérieur de la caméra. Cette relation permet de projeter les données acquises par le capteur dans l’espace objet, et ainsi de reconstruire une image pixel par pixel à la profondeur choisie. En inversant les équations, nous avons montré qu’il était possible de créer des images plénoptiques synthétiques. La reconstruction de ces données synthétiques nous a permis de valider la cohérence des résultats après reconstruction, et de quantifier la précision de ce nouvel algorithme.Cet algorithme permet de reconstruire séparément chaque plan de profondeur. Dans chacun d’entre eux, les éléments physiques qui appartiennent réellement à ce plan sont nets, alors que les objets des plans adjacents sont flous. Nous utilisons cette propriété de contraste pour extraire l’information de profondeur dans les images refocalisées. Nous avons sélectionné plusieurs méthodes provenant du domaine de « depth from focus » et avons étudié leurs efficacités sur nos images.Dans le cadre d’une collaboration européenne, nous avons construit la première caméra plénoptique dans les rayons X au synchrotron PETRA III. Grâce au travail réalisé pendant cette thèse, nous avons choisi les configurations optiques les plus adaptées aux optiques disponibles et aux caractéristiques du faisceau. Nous avons réalisé le montage de la caméra, acquis des images plénoptiques en rayons X, refocalisé ces images avec notre algorithme, et vérifié les résolutions optiques. Les méthodes de « depth from focus » appliquées sur les images refocalisées ont permis de retrouver la profondeur attendue. Ce travail correspond aux premières images acquises avec une caméra plénoptique en rayons X
Plenoptic imaging is a technique that acquires spatial and angular information of the light rays incoming from a scene. After a single acquisition, numerical data treatment allows image manipulation such as synthetic aperture, changing viewpoint, refocusing at different depths, and consequently 3D reconstruction of the scene. Visible plenoptic has been widely studied. However, transposition from visible to X-rays has never been done and remains challenging. X-ray plenoptic would be beneficial to the X-ray imaging panorama. A single acquisition should be sufficient to reconstruct a volume, against 1000’s for X-ray tomography that is the today reference in 3D X-ray imaging.In this thesis, we consider plenoptic camera composed of a main lens, a microlens array and a detector. So far, two different configurations have been developed: the traditional and the focused plenoptic setups. Although these configurations are usually studied separately, they only differ by the distances between the optical elements. These two configurations were studied in detail to choose the most suitable for X-ray imaging, considering the constraints of X-ray optics. We observed a full continuity between the two systems. Therefore, we extended the previous work to more general formulas about optical configuration and theoretical resolutions. Theory about resolution along the depth axis was refined, as depth reconstruction and extraction are the main interest of X-ray plenoptic. Specific study was done on the evolution of contrast along depth as being a key parameter for depth reconstruction. We realized that contrast decreases when moving away from a privileged depth. This is important to consider as it can affect image reconstruction and quality of depth extraction.We also worked on refocusing algorithms. The refocusing algorithms are usually developed for each configuration separately. We worked to go beyond this separation. We developed a new algorithm valid for any configurations. Moreover, our algorithm is based on real distances between the optical elements, allowing generating images at any distances from the plenoptic camera. We defined a new parameterization between object and image spaces. Using geometrical optics, we calculated the matrix transformation between the two spaces. This allows back-projecting data from the acquired raw image to the object space, and reconstructing the pixels one by one, until the whole object. With this algorithm, we were able to simulate the process of image acquisition, and create synthetic plenoptic data. Reconstruction of these data was used to quantify the accuracy of the novel algorithm and prove its consistency.The refocusing algorithm allows reconstructing the depth planes one by one. Each refocused plane contains information about the whole 3D scene that has to be disentangled. The elements physically present at the refocused depth are intrinsically sharp, whereas the ones located at other depths are blurred. We used this contrast property to extract depth from the refocused images. We tested several existing methods derived from the field of depth from focus and studied their efficiency when applied to our images.In collaboration with European teams, we realized the first X-ray plenoptic camera that was tested at P05 beamline of PETRA III synchrotron. Based on the theoretical work developed in this thesis, we defined the best optical configuration, mounted the plenoptic camera, acquired X-ray plenoptic images, numerically refocused them using the new algorithm and verified the experimental resolutions and contrasts. Depth from focus techniques applied on the refocused stack allow to retrieve the expected depth plane. These are the first images acquired with an X-ray plenoptic camera

Este trabalho avalia a distribuição de dose recebida por trabalhadores envolvidos nos procedimentos de radiologia veterinária portátil digital e verifica a redução da dose obtida com a utilização de equipamentos de proteção individual. Para esta avaliação foram feitas medições utilizando dosímetros termoluminescentes tipo TLD-100, posicionados em sete diferentes pontos do corpo dos assistentes: mãos, tórax (por fora do avental), tireoide (por dentro do avental), cantos dos olhos esquerdo e direito e centro dos olhos e em cinco pontos diferente no médico veterinário: tórax (por fora do avental), tireoide (por dentro do avental), cantos dos olhos esquerdo e direito e centro dos olhos. As doses ocupacionais foram avaliadas em 63 procedimentos radiográficos de cães realizados com 49 assistentes e um médico veterinário na região metropolitana de Curitiba, PR. Os resultados mostram a importância do uso do protetor de tireoide e avental de chumbo para a redução da dose recebida pelos profissionais. As doses dos assistentes que seguraram os animais foram mais altas na região das mãos. Este estudo mostra a necessidade de medidas adicionais de proteção e a implementação de mecanismos de treinamento em proteção radiológica para os médicos e assistentes que trabalham com radiologia portátil digital.
This study evaluates the distribution of the dose received by work-people involved in portable digital veterinary radiology procedures and checks the dose reduction obtained with the use of individual protection equipments. For this evaluation measurements were made using TLD-100 thermoluminescent dosimeters,positioned at seven different spots on the body of the assistants: hands, chest (outside the apron), thyroid (inside the apron), left and right eye corners and at the forehead, and in five different spots in the veterinarian: chest (outside the apron), thyroid (inside the apron), left and right eye corners and the center of the eyes. The dosage was evaluated through the 63 procedures performed with 49 assistants and a veterinarian in the metropolitan region of Curitiba, PR. The results show the importance of using thyroid protection and lead aprons to reduce the dosage received by the veterinarian and assistants. The dosages of the assistants who held the animals were higher in the areas of the hands. This study shows the need for additional protective measurements and the implementation of training mechanisms in radiation protection for physicians and assistants who work with portable digital radiology.

Orientadores: Antonio Celso Fonseca de Arruda, Roberto de Alencar Lotufo
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica
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Resumo: A tomografia computadorizada de raios-x tem extrapolado a área médica e ganhado campo em inúmeras aplicações onde se faz necessária a interpretação (qualitativa e quantitativa) da estrutura interna de um material opaco, sem destruí-lo. O presente trabalho demonstra a aplicação desta técnica em ensaios não destrutivos, utilizando-se amostras de materiais e componentes de diferentes densidades e geometrias, com defeitos simulados e reais, ensaiados em tomógrafos médicos. Demonstra-se, também, o uso da técnica na caracterização de filtros eletroquímicos usados para remoção de agentes contaminantes (no caso, zinco) de efluentes industriais. Foram usadas técnicas de processamento digital de imagens (sistema Khoros) para a caracterização dos defeitos encontrados, através da medida do coeficiente de atenuação do material em regiões de interesse, e por meio do cálculo de parâmetros dimensionais tais como área e perímetro. Foram aplicadas operações de filtragem matemática para a correção do efeito de endurecimento de feixe, verificado nas imagens de materiais metálicos, sobretudo no alumínio. Devido à sua natureza qualitativa e quantitativa, a tomografia computadorizada de raios-x demonstrou ser uma ferramenta promissora em ensaios não destrutivos de materiais. Este trabalho demonstra e reforça sua aplicabilidade através do uso de processamento digital de imagens
Abstract: X-ray computed tomography (XCT), originally developed for medical purposes is becoming increasingly applied to several applications where it is necessary the interpretation of the internal structure of an object nondestructively. The present work shows the application of this technique to nondestructive testing using materiaIs and components of different density and geometry, with simulated and real defects tested in a medical scanner. Characterization of electrochemical filters used to remove contamination agents (in this case, zinc) in industrial effluents, by XCT technique is also described. Digital image processing have been used (software Khoros) for defects characterization, determining the attenuation coefficient in regions of interest and measuring parameters like area and perimeter. Digital filtering operations have been applied for beam hardening correction in metallic materiaIs images, mainly aluminum. Due its qualitative and quantitative nature, XCT technique established to be a promising tool of nondestructive materiaIs evaluation and this work emphasizes its applicability through digital image processing
Mestrado
Materiais e Processos de Fabricação
Mestre em Engenharia Mecânica

Orientador: Antonio Celso Fonseca de Arruda
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica
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Resumo: O objetivo deste trabalho foi o desenvolvimento de metodologias para o estudo de filtros e processos de filtração, utilizando a tomografia de raios-X, técnicas de processamento digital de imagens e simulação numérica. Os ensaios convencionais utilizados pelos fabricantes são realizados através da medida de parâmetros, tais como pressão e vazão, em pontos localizados a montante e a jusante do filtro. Estes ensaios não são eficientes na caracterização de defeitos e não revelam como ocorre o processo de saturação no interior do filtro. Neste trabalho, a tomografia de raios-X foi utilizada para duas finalidades básicas: estudar a distribuição de contaminantes e analisar defeitos no interior de elementos filtrantes. Os modelos de filtração encontrados na literatura não levam em conta o efeito do acúmulo de contaminantes no desempenho do filtro ao longo do processo de filtração. Neste trabalho, foi desenvolvido um modelo acoplando-se as equações de filtração com as equações fenomenológicas (lei de Darcy e equação da continuidade), de tal forma que o acúmulo de partículas no meio poroso (filtro) fosse considerado na simulação do processo de filtração. Os resultados demonstraram que o processo de saturação no interior dos elementos analisados não ocorre de forma homogênea, ou seja, o acúmulo de partículas é predominante em determinadas regiões. Em geral, há formação de canais preferenciais e o espaço interno do filtro não é totalmente utilizado na captura de partículas. Demonstrou-se também que, em alguns casos, o comportamento do filtro não é coerente com a especificação do fabricante. Foi possível, por fim, a utilização dos dados experimentais, obtidos via tomografia, para a validação do modelo teórico desenvolvido
Abstract: The development of methods for analysis of filters and filtration process, using X-ray computerized tomography, digital image processing and numerical simulation, was the objective of this work. Tests conventionally used by filter manufacturers are made through the measurement ofparameters, such as flow and pressure, at upstream and downstream ofthe filter. These tests are not efficient in the characterization of defects and do not reveal how the saturation process occurs within the filter. In this work, X-ray computerized tomography was used for two basic purposes: to evaluate contaminant distribution and to detect defects within the interior of the filter elements. The filtration models found in the literature do not consider the effect of contaminant concentration on the filter efficiency during the filtration processo In this work, filtration equations and phenomenological equations (Darcy's law and continuity equation) were coupled and a model that takes into account the contaminant accumulation on the filter performance was developed. The results demonstrated that the saturation process within the analyzed filters is not homogeneous, that is, the accumulation of partic1es is predominant in some regions. Generally, there are preferential channels and the interior of the filter elements is not totally utilized. In some cases, it was also demonstrated that the filter behavior does not agree with the manufacturer specifications. Finally, it was possible to use the experimental data obtained with X-ray computerized tomography, in order to validate the theoretical developed model
Doutorado
Materiais e Processos de Fabricação
Doutor em Engenharia Mecânica

Увод: Пинеална жлезда је неуроендокрини, циркумвентрикуларни орган филогенетски пореклом органа вида. Калцификације пинеалне жлезде су чест налаз приликом радиолошких претрага, без још увек довољно доказа да ли су оне нормалан налаз. Магнетна резонанца описује три морфолошка типа пинеалне жлезде. Циљеви: Утврдити степен корелације морфолошких типова пинеалне жлезде утврђених патохистолошким налазом са налазом компјутеризоване томографије, као и степен корелације присуства калцификација у пинеалној жлезди утврђених патохистолошким налазом и налазом компјутеризоване томографије. Утврдити степен калцификације пинеалне жлезде патохистолошким налазом у зависности од старости. Материјал и методе: Макроскопском морфолошком и микроскопском, хистолошком анализом обухваћено је 111 изолованих пинеалних жлезди осoба оба пола, не млађих од 18 година од којих је 27 снимљено апаратом Somatom Sensation 64 са дебљинама реконструисаних пресека 5 и 1mm, а још 9 апаратом Somatom Emotion 16. Резултати: Постоји статистички значајна разлика у одређивању сва три дијаметра епифизе петомилиметарским реконструкцијама, и при утврђивању два дијаметра једномилиметарским реконструкцијама. Постоји статистички значајна разлика у утврђивању морфолошких типова хистолошком и методом компјутеризоване томографије. Присутна је позитивна корелација калцификованости жлезде одређене мерењем њене густине у Хаунсфилдовим јединицама и утврђене микроскопски. Калцификованост пинеалног паренхима не корелира старости. Закључак: Наша студија је показала да су једномилиметарске реконструкције тачније у одређивању дијаметара жлезде. Макроскопским и микроскопским мерењем утврђена су сва три типа пинеалне жлезде описана магнетнорезонантним осликавањем. Утврђена је статистички значајна повезаност густине пинеалне жлезде измерене у Хаунсфилдовим јединицама на једномилиметарским реконструкцијама и степена калцификованости израженог у процентима. Није утврђена повезаност калцификованости епифизе мерене микроскопски и старости.
Uvod: Pinealna žlezda je neuroendokrini, cirkumventrikularni organ filogenetski poreklom organa vida. Kalcifikacije pinealne žlezde su čest nalaz prilikom radioloških pretraga, bez još uvek dovoljno dokaza da li su one normalan nalaz. Magnetna rezonanca opisuje tri morfološka tipa pinealne žlezde. Ciljevi: Utvrditi stepen korelacije morfoloških tipova pinealne žlezde utvrđenih patohistološkim nalazom sa nalazom kompjuterizovane tomografije, kao i stepen korelacije prisustva kalcifikacija u pinealnoj žlezdi utvrđenih patohistološkim nalazom i nalazom kompjuterizovane tomografije. Utvrditi stepen kalcifikacije pinealne žlezde patohistološkim nalazom u zavisnosti od starosti. Materijal i metode: Makroskopskom morfološkom i mikroskopskom, histološkom analizom obuhvaćeno je 111 izolovanih pinealnih žlezdi osoba oba pola, ne mlađih od 18 godina od kojih je 27 snimljeno aparatom Somatom Sensation 64 sa debljinama rekonstruisanih preseka 5 i 1mm, a još 9 aparatom Somatom Emotion 16. Rezultati: Postoji statistički značajna razlika u određivanju sva tri dijametra epifize petomilimetarskim rekonstrukcijama, i pri utvrđivanju dva dijametra jednomilimetarskim rekonstrukcijama. Postoji statistički značajna razlika u utvrđivanju morfoloških tipova histološkom i metodom kompjuterizovane tomografije. Prisutna je pozitivna korelacija kalcifikovanosti žlezde određene merenjem njene gustine u Haunsfildovim jedinicama i utvrđene mikroskopski. Kalcifikovanost pinealnog parenhima ne korelira starosti. Zaključak: Naša studija je pokazala da su jednomilimetarske rekonstrukcije tačnije u određivanju dijametara žlezde. Makroskopskim i mikroskopskim merenjem utvrđena su sva tri tipa pinealne žlezde opisana magnetnorezonantnim oslikavanjem. Utvrđena je statistički značajna povezanost gustine pinealne žlezde izmerene u Haunsfildovim jedinicama na jednomilimetarskim rekonstrukcijama i stepena kalcifikovanosti izraženog u procentima. Nije utvrđena povezanost kalcifikovanosti epifize merene mikroskopski i starosti.
Introduction: Pineal gland is a small neuroendocrine, circumventricular organ wich evolved from the eye. Calcifications were incidentally discovered and frequently without a proof whether they were normal or abnormal. Magnetic resonance imaging describes three morphological types. Aim: To determine if there is a correlation between pineal gland morphology types and calcifications established with histology and with computed tomography (CT) and if there is the correlation between calcifications and age. Method of work and material: Macroscopic and mycroscopic analysis encounted 111 isolated pineal glands of both sexes, no younger than 18, from wich 27 was examed with Somatom Sensation 64 and 9 with Somatom Emotion 16 with 5mm and 1mm reformated pictures. Results: All three diameters measured on 5mm reformated pictures and two measured on 1mm reformated pictures differed statistically compared to diameters measured macroscopically. There was siginificant difference between morphological types established on computed tomography and macroscopically. Pineal gland calcifications measured microscopically and with CT correlated positivelly. Pineal gland calcifications were not dependant on the patients age. Conclusion: Allthough 1mm reformated pictures are more accurate than 5mm, the pineal gland morpholgy types determined macroscopically and with CT are not correlated. However, calcification measurement with CT correlates with the microscopic measurement. Calcifications measured microscopically are not correlated with age.

This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.

This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.
Islamic University of Omdurman and the Ministry of Higher Education in Sudan

This thesis addresses the three principal questions concerning the development of CT urography for investigating haematuria and each question is the subject of a separate chapter. The questions are: What is the reasoning behind using CT urography? What is the optimum diagnostic strategy using CT urography? What are the problems with using CT urography and how may solutions be provided? Haematuria can signify serious disease such as urinary tract stones, renal cell cancer, upper tract urothelial cancer (UTUC) and bladder cancer (BCa). CT urography is defined as contrast enhanced CT examination of kidneys, ureters and bladder. The technique used here includes unenhanced, nephrographic and excretory-phases for optimized diagnosis of stones, renal masses and urothelial cancer respectively. The reasoning behind using excretory-phase CT urography for investigating haematuria is based on results showing its high diagnostic accuracy for UTUC and BCa. Patients with haematuria are classified as low risk or high risk for UTUC and BCa, by a risk score, determined by the presence/absence of risk factors: age > 50 years, visible or nonvisible haematuria, history of smoking and occupational exposure. The optimum diagnostic strategy for patients at high risk for urothelial cancer, uses CT urography as a replacement test for ultrasonography and intravenous urography and as a triage test for flexible and rigid cystoscopy, resulting in earlier diagnosis and potentially improving prognosis. For patients at low risk, ultrasonography, unenhanced and nephrographic-phase CT urography are proposed as initial imaging tests. Problems with using CT urography include false positive results for UTUC, which are eliminated by retrograde ureteropyelography-guided biopsy, an innovative technique, for histopathological confirmation of diagnosis. Recommendations for the NHS and possible future developments are discussed. CT urography, including excretory-phase imaging, is recommended as the initial diagnostic imaging test before cystoscopy for patients with haematuria at high risk for urothelial cancer.

Les travaux de cette thèse s’inscrivent dans le cadre du planning de traitements minimalement invasifs des lésions des artères coronaires. Le cardiologue réalise un examen coronarographique, puis dans la continuité, une angioplastie transluminale. L’angiographie rotationnelle à rayons X permet de visualiser sous différentes incidences 2D la lumière des artères coronaires sur plusieurs cycles cardiaques et aussi d’obtenir une reconstruction 3D+T des arbres coronaires. A partir de cette séquence, notre objectif est de déterminer automatiquement une incidence optimale 2D du segment sténosé compatible avec les angles du C-arm afin d’aider le cardiologue lors de l’intervention.Différentes étapes sont considérées pour calculer la position angulaire optimale du C-arm. Afin de suivre la zone de lésion durant le cycle cardiaque, une première méthode est proposée pour mettre en correspondance tous les arbres de la séquence 3D+T. Tout d’abord, un appariement deux à deux des arbres successifs est réalisé afin de construire un arbre d’union. Ces derniers sont ensuite fusionnés afin d’obtenir un arbre mosaïque représentant l’arbre le plus complet de la séquence. L’utilisation de mesures de similarités géométriques et hiérarchiques ainsi que l’insertion de nœuds artificiels permet de prendre en compte les différents mouvements non-rigides des artères coronaires subits au cours du cycle cardiaque et les variations topologiques dû à leurs extractions. Cet appariement nous permet de proposer une deuxième méthode afin d’obtenir une vue angiographique 2D optimale de la zone de lésion tout le long du cycle cardiaque. Cette incidence est proposée spécifiquement pour trois types de région d’intérêt (segment unique, segment multiple ou bifurcation) et est calculée à partir de quatre critères (raccourcissement, chevauchement interne et externe ou angle d’ouverture de bifurcation). Une vue 2D déployée du segment projeté avec le moins de superposition avec les structures vasculaires avoisinantes est obtenue. Nous donnons également la possibilité au cardiologue d’avoir une incidence optimale privilégiant soit le déploiement du stent ou soit le guidage d’outils de la racine de l’arbre à la zone sténosée. Nos différents algorithmes ont été évalués sur une séquence réelle de 10 phases segmentées à partir d’un CT et de 41 séquences simulées
The thesis work deals with the planning of minimally invasive surgery of coronary artery lesions. The physician performs a coronarography following by a percutaneous transluminal angioplasty. The X-ray rotational angiography permits to visualize the lumen artery under different projection angles in several cardiac cycles. From these 2D projections, a 3D+T reconstruction of coronary arteries can be obtained. Our goal is to determine automatically from this 3D+T sequence, the optimal angiographic viewing angle of the stenotic segment. Several steps are proposed to compute the optimal angular position of the C-arm. Firstly, a mosaic-based tree matching algorithm of the 3D+T sequence is proposed to follow the stenotic lesion in the whole cardiac cycle. A pair-wise inexact tree matching is performed to build a tree union between successive trees. Next, these union trees are merged to obtain the mosaic tree which represents the most complete tree of the sequence. To take into account the non-rigid movement of coronary arteries during the cardiac cycle and their topology variations due to the 3D reconstruction or segmentation, similarity measures based on hierarchical and geometrical features are used. Artificial nodes are also inserted. With this global tree sequence matching, we propose secondly a new method to determine the optimal viewing angle of the stenotic lesion throughout the cardiac cycle. This 2D angiographic view which is proposed for three regions of interest (single segment, multiple segment or bifurcation) is computed from four criteria: the foreshortening, the external and internal overlap and the bifurcation opening angle rates. The optimal view shows the segment in its most extended and unobstructed dimension. This 2D view can be optimal either for the deployment of the stent or for the catheter guidance (from the root to the lesion). Our different algorithms are evaluated on real sequence (CT segmentation) and 41 simulated sequences

碩士
元培科學技術學院
影像醫學研究所
94
Abstract We are presently faced with the threat of an avian flu outbreak in Taiwan. In response to this threat each unit in the hospital must develop a protocol for handling infected patients to protect the medical personnel and the patients being treated in the hospital. This abstract will discuss two issues the radiology department will have to deal with the possibility of an outbreak of avian flu. The first topic is suggestions for updating infectious control procedures in the radiology department. The second topic is a description of the dual energy X-ray image technique for acute respiratory diseases. Patients with an acute infectious disease will have symptoms of upper respiratory infection on their way to the hospital. It is often necessary to order a chest X ray based on the patient’s symptoms. Avian Flu and SARS have similar symptoms therefore proper precautions must be taken. We learned during the SARS outbreak the physicians and medical personnel did not take enough precautions. They did not have a clear idea of how easily the disease could spread, that strong measures of protection that were needed or they neglected using the type of protection recommended. Some medical personnel got infected and some sacrificed their lives as a result of the lack of proper precautions against the spread of SARS. There needs to be new protocol for examining patients in order to prevent the spread of the disease. Even so, X- ray technicians must be careful to use precautions while performing the X-Rays. Before putting on the outer protection equipment, they must spray themselves with phosphor from head to foot. Only after being sprayed can the technician wear the protective covering. After the work is completed, the protective clothing will be taken off and should be wrapped tightly in a bundle inside out. The protective clothes and the technician will be exposed to ultraviolet to check for any relation with the phosphor. If there is no reaction, the protective clothing will be placed into an infectious control container. The technicians are then clear to leave the work place. The traditional X-Ray technique currently used in the hospital does not allow for early diagnosis of pulmonary consolidation. There is a new X-Ray technique that allows for early diagnosis and containment of the disease. Breaking out of the traditional routine imaging technique gives us a golden opportunity for early treatment. When a patient has cough and fever, he may be suspeeted of having respiratory infection. X- rays are usually used to diagnose the infection. However, early pulmonary consolidation has a relatively low absorption coefficient in the early stage alveolar infiltration. There is an x-ray imaging technique that can be used to contrast images to find pulmonary consolidation in the early stages. Computer Radiography uses a Dual-Energy Radiography to produce two different energy images: low-energy images and high-energy images. The images are then stored in the Picture Archiving Communication stem (PACS). After transmission and storage, it is possible to use subtraction technology so that pulmonary consolidation can be seen more clearly in the early stages of infection. The low energy image is organized by the computer in many windows on the screen in different widths and values. The high-energy image is organized together with the low energy image and can cover (mask) some parts of the low-energy image. The high-energy images can be subtracted (eliminated) one by one from the low energy images. After the high-energy images are subtracted (eliminated), the contrast image of tissues will appear more clearly on the screen. Patients with early stage pulmonary consolidation have relatively low absorption coefficient of the X-rays. The use of the subtraction method allows the pulmonary consolidation to be seen more easily. Early identification of pulmonary consolidation seen in the contrast image allows for early treatment of the patient. The staff working in the radiology department must not only use safety practices to protect themselves from infection. but also transmit information about any infections quickly and effectively to the hospital staff in order to avoid further spread of the infection. We should be rigorous in developing procedures and taking precautions to fight against the threat of Avian Flu. We can break out of using the traditional X-Ray techniques and experiment with new methods that are more effective and sensitive for diagnosing infections early. The main focus of this abstract is to introduce a dual-energy X-ray technique that will help us obtain the correct diagnosis and help the patients with acute infections to get early and effective treatment.

Thesis (Ph. D.)--University of Wisconsin-Madison, 1987.
Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 153-168).

Contrast-enhanced mammography (CEM) relies on visualizing the growth of new blood vessels (i.e. tumor angiogenesis) to provide sufficient materials for cell proliferation during the development of cancer. Since cancers will accumulate an injected contrast agent more than other tissues, it is possible to use one of several methods to enhance the area of lesions in the x-ray image and remove the contrast of normal tissue. Large area flat panel detectors may be used for CEM wherein the subtraction of two acquired images is used to create the resulting enhanced image. There exist several methods to acquire the images to be subtracted, which include temporal subtraction (pre- and post-contrast images) and dual-energy subtraction (low- and high-energy images), however these methods suffer from artifacts due to patient motion between image acquisitions. In this research the use of a multilayer flat panel detector is examined for CEM that is designed to acquire both (low- and high-energy) images simultaneously, thus avoiding motion artifacts in the resulting subtracted image. For comparison, a dual-energy technique prone to motion artifacts that uses a single-layer detector is also investigated. Both detectors are evaluated and optimized using amorphous selenium as the x-ray to charge conversion material, however the theoretical analysis could be extended to other conversion materials. Experimental results of single pixel prototypes of both multilayer and single-layer detectors are also discussed and compared to theoretical results. For a more comprehensive analysis, the motion artifacts present in dual-exposure techniques are modeled and the performance degradation due to motion artifacts is estimated. The effects of noise reduction techniques are also evaluated to determine potential image quality improvements in CEM images.

X-ray computed tomography (CT) imaging constitutes one of the most widely used diagnostic tools in radiology today with nearly 85 million CT examinations performed in the U.S in 2011. CT imparts a relatively high amount of radiation dose to the patient compared to other x-ray imaging modalities and as a result of this fact, coupled with its popularity, CT is currently the single largest source of medical radiation exposure to the U.S. population. For this reason, there is a critical need to optimize CT examinations such that the dose is minimized while the quality of the CT images is not degraded. This optimization can be difficult to achieve due to the relationship between dose and image quality. All things being held equal, reducing the dose degrades image quality and can impact the diagnostic value of the CT examination.

A recent push from the medical and scientific community towards using lower doses has spawned new dose reduction technologies such as automatic exposure control (i.e., tube current modulation) and iterative reconstruction algorithms. In theory, these technologies could allow for scanning at reduced doses while maintaining the image quality of the exam at an acceptable level. Therefore, there is a scientific need to establish the dose reduction potential of these new technologies in an objective and rigorous manner. Establishing these dose reduction potentials requires precise and clinically relevant metrics of CT image quality, as well as practical and efficient methodologies to measure such metrics on real CT systems. The currently established methodologies for assessing CT image quality are not appropriate to assess modern CT scanners that have implemented those aforementioned dose reduction technologies.

Thus the purpose of this doctoral project was to develop, assess, and implement new phantoms, image quality metrics, analysis techniques, and modeling tools that are appropriate for image quality assessment of modern clinical CT systems. The project developed image quality assessment methods in the context of three distinct paradigms, (a) uniform phantoms, (b) textured phantoms, and (c) clinical images.

The work in this dissertation used the “task-based” definition of image quality. That is, image quality was broadly defined as the effectiveness by which an image can be used for its intended task. Under this definition, any assessment of image quality requires three components: (1) A well defined imaging task (e.g., detection of subtle lesions), (2) an “observer” to perform the task (e.g., a radiologists or a detection algorithm), and (3) a way to measure the observer’s performance in completing the task at hand (e.g., detection sensitivity/specificity).

First, this task-based image quality paradigm was implemented using a novel multi-sized phantom platform (with uniform background) developed specifically to assess modern CT systems (Mercury Phantom, v3.0, Duke University). A comprehensive evaluation was performed on a state-of-the-art CT system (SOMATOM Definition Force, Siemens Healthcare) in terms of noise, resolution, and detectability as a function of patient size, dose, tube energy (i.e., kVp), automatic exposure control, and reconstruction algorithm (i.e., Filtered Back-Projection– FPB vs Advanced Modeled Iterative Reconstruction– ADMIRE). A mathematical observer model (i.e., computer detection algorithm) was implemented and used as the basis of image quality comparisons. It was found that image quality increased with increasing dose and decreasing phantom size. The CT system exhibited nonlinear noise and resolution properties, especially at very low-doses, large phantom sizes, and for low-contrast objects. Objective image quality metrics generally increased with increasing dose and ADMIRE strength, and with decreasing phantom size. The ADMIRE algorithm could offer comparable image quality at reduced doses or improved image quality at the same dose (increase in detectability index by up to 163% depending on iterative strength). The use of automatic exposure control resulted in more consistent image quality with changing phantom size.

Based on those results, the dose reduction potential of ADMIRE was further assessed specifically for the task of detecting small (<=6 mm) low-contrast (<=20 HU) lesions. A new low-contrast detectability phantom (with uniform background) was designed and fabricated using a multi-material 3D printer. The phantom was imaged at multiple dose levels and images were reconstructed with FBP and ADMIRE. Human perception experiments were performed to measure the detection accuracy from FBP and ADMIRE images. It was found that ADMIRE had equivalent performance to FBP at 56% less dose.

Using the same image data as the previous study, a number of different mathematical observer models were implemented to assess which models would result in image quality metrics that best correlated with human detection performance. The models included naïve simple metrics of image quality such as contrast-to-noise ratio (CNR) and more sophisticated observer models such as the non-prewhitening matched filter observer model family and the channelized Hotelling observer model family. It was found that non-prewhitening matched filter observers and the channelized Hotelling observers both correlated strongly with human performance. Conversely, CNR was found to not correlate strongly with human performance, especially when comparing different reconstruction algorithms.

The uniform background phantoms used in the previous studies provided a good first-order approximation of image quality. However, due to their simplicity and due to the complexity of iterative reconstruction algorithms, it is possible that such phantoms are not fully adequate to assess the clinical impact of iterative algorithms because patient images obviously do not have smooth uniform backgrounds. To test this hypothesis, two textured phantoms (classified as gross texture and fine texture) and a uniform phantom of similar size were built and imaged on a SOMATOM Flash scanner (Siemens Healthcare). Images were reconstructed using FBP and a Sinogram Affirmed Iterative Reconstruction (SAFIRE). Using an image subtraction technique, quantum noise was measured in all images of each phantom. It was found that in FBP, the noise was independent of the background (textured vs uniform). However, for SAFIRE, noise increased by up to 44% in the textured phantoms compared to the uniform phantom. As a result, the noise reduction from SAFIRE was found to be up to 66% in the uniform phantom but as low as 29% in the textured phantoms. Based on this result, it clear that further investigation was needed into to understand the impact that background texture has on image quality when iterative reconstruction algorithms are used.

To further investigate this phenomenon with more realistic textures, two anthropomorphic textured phantoms were designed to mimic lung vasculature and fatty soft tissue texture. The phantoms (along with a corresponding uniform phantom) were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Scans were repeated a total of 50 times in order to get ensemble statistics of the noise. A novel method of estimating the noise power spectrum (NPS) from irregularly shaped ROIs was developed. It was found that SAFIRE images had highly locally non-stationary noise patterns with pixels near edges having higher noise than pixels in more uniform regions. Compared to FBP, SAFIRE images had 60% less noise on average in uniform regions for edge pixels, noise was between 20% higher and 40% lower. The noise texture (i.e., NPS) was also highly dependent on the background texture for SAFIRE. Therefore, it was concluded that quantum noise properties in the uniform phantoms are not representative of those in patients for iterative reconstruction algorithms and texture should be considered when assessing image quality of iterative algorithms.

The move beyond just assessing noise properties in textured phantoms towards assessing detectability, a series of new phantoms were designed specifically to measure low-contrast detectability in the presence of background texture. The textures used were optimized to match the texture in the liver regions actual patient CT images using a genetic algorithm. The so called “Clustured Lumpy Background” texture synthesis framework was used to generate the modeled texture. Three textured phantoms and a corresponding uniform phantom were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Images were reconstructed with FBP and SAFIRE and analyzed using a multi-slice channelized Hotelling observer to measure detectability and the dose reduction potential of SAFIRE based on the uniform and textured phantoms. It was found that at the same dose, the improvement in detectability from SAFIRE (compared to FBP) was higher when measured in a uniform phantom compared to textured phantoms.

The final trajectory of this project aimed at developing methods to mathematically model lesions, as a means to help assess image quality directly from patient images. The mathematical modeling framework is first presented. The models describe a lesion’s morphology in terms of size, shape, contrast, and edge profile as an analytical equation. The models can be voxelized and inserted into patient images to create so-called “hybrid” images. These hybrid images can then be used to assess detectability or estimability with the advantage that the ground truth of the lesion morphology and location is known exactly. Based on this framework, a series of liver lesions, lung nodules, and kidney stones were modeled based on images of real lesions. The lesion models were virtually inserted into patient images to create a database of hybrid images to go along with the original database of real lesion images. ROI images from each database were assessed by radiologists in a blinded fashion to determine the realism of the hybrid images. It was found that the radiologists could not readily distinguish between real and virtual lesion images (area under the ROC curve was 0.55). This study provided evidence that the proposed mathematical lesion modeling framework could produce reasonably realistic lesion images.

Based on that result, two studies were conducted which demonstrated the utility of the lesion models. The first study used the modeling framework as a measurement tool to determine how dose and reconstruction algorithm affected the quantitative analysis of liver lesions, lung nodules, and renal stones in terms of their size, shape, attenuation, edge profile, and texture features. The same database of real lesion images used in the previous study was used for this study. That database contained images of the same patient at 2 dose levels (50% and 100%) along with 3 reconstruction algorithms from a GE 750HD CT system (GE Healthcare). The algorithms in question were FBP, Adaptive Statistical Iterative Reconstruction (ASiR), and Model-Based Iterative Reconstruction (MBIR). A total of 23 quantitative features were extracted from the lesions under each condition. It was found that both dose and reconstruction algorithm had a statistically significant effect on the feature measurements. In particular, radiation dose affected five, three, and four of the 23 features (related to lesion size, conspicuity, and pixel-value distribution) for liver lesions, lung nodules, and renal stones, respectively. MBIR significantly affected 9, 11, and 15 of the 23 features (including size, attenuation, and texture features) for liver lesions, lung nodules, and renal stones, respectively. Lesion texture was not significantly affected by radiation dose.

The second study demonstrating the utility of the lesion modeling framework focused on assessing detectability of very low-contrast liver lesions in abdominal imaging. Specifically, detectability was assessed as a function of dose and reconstruction algorithm. As part of a parallel clinical trial, images from 21 patients were collected at 6 dose levels per patient on a SOMATOM Flash scanner. Subtle liver lesion models (contrast = -15 HU) were inserted into the raw projection data from the patient scans. The projections were then reconstructed with FBP and SAFIRE (strength 5). Also, lesion-less images were reconstructed. Noise, contrast, CNR, and detectability index of an observer model (non-prewhitening matched filter) were assessed. It was found that SAFIRE reduced noise by 52%, reduced contrast by 12%, increased CNR by 87%. and increased detectability index by 65% compared to FBP. Further, a 2AFC human perception experiment was performed to assess the dose reduction potential of SAFIRE, which was found to be 22% compared to the standard of care dose.

In conclusion, this dissertation provides to the scientific community a series of new methodologies, phantoms, analysis techniques, and modeling tools that can be used to rigorously assess image quality from modern CT systems. Specifically, methods to properly evaluate iterative reconstruction have been developed and are expected to aid in the safe clinical implementation of dose reduction technologies.

Dissertation

Mercury (Hg) compounds are some of the most toxic compounds of any heavy metal on earth. Due to long-range transport from point sources Hg can be found world-wide in air, soil, water, and living organisms. Mercury compounds can cause a number of adverse effects, with the unborn fetus, infants, and children being most susceptible. Zebrafish (Danio rerio) are an excellent vertebrate model system for toxicological studies, including developmental effects. The overall objective of this research was to investigate the effects of inorganic forms of Hg in zebrafish larvae. Unique accumulation patterns were observed using synchrotron X-ray fluorescence imaging after zebrafish were exposed to one of four Hg compounds (i.e. mercuric chloride, mercury bis-L-cysteineate, methylmercury chloride, methylmercury L-cysteineate). Specifically, we noted chemical form dependant and tissue-specific Hg accumulation including the sensory cells of the olfactory epithelia and the neuromasts. Phenylthiourea (PTU) is commonly used to block zebrafish melanogenesis to generate transparent larvae to aid with enhanced visualization of immunohistochemical and vital stains. It was determined that PTU dramatically alters Hg toxicity through chemical interaction with Hg so that further studies were conducted in the absence of PTU. To investigate the effects of Hg on primary neurons, the immunohistochemistry protocol using anti-acetylated tubulin was performed and the results demonstrated that mercuric chloride damages primary neurons particularly in the olfactory pits. To study potential detoxification of Hg in zebrafish we examined the efficacy of two sequestration agents, dimercaptosuccinic acid and alpha lipoic acid, as well as endogenous selenium. The levels of Hg were not significantly lower following treatment with either sequestration agent under the conditions used in this research. Previous work examining the antagonistic relationship between Hg and selenium has been conducted by dosing animals with both Hg and selenium (Se). We discovered a mixed chalcogenide of the general form HgSxSe(1-x) forming in vivo following exposure to mercuric chloride without the addition of selenium. Indeed the selenium may have been remobilized from natural stores in the pigment spots. The research presented herein demonstrates that the target tissues for Hg depend strongly on chemical form. In particular inorganic Hg can accumulate in a number of important tissues including sensory systems. The formation of insoluble and non-toxic HgSxSe(1-x) in zebrafish larvae suggests that endogenous selenium may play critical roles in modulating toxicity.

Cartilage tissue engineering has been emerging as a promising therapeutic approach, where engineered constructs or scaffolds are used as temporary supports to promote regeneration of functional cartilage tissue. Hybrid constructs fabricated from cells, hydrogels, and solid polymeric materials show the most potential for their enhanced biological and mechanical properties. However, fabrication of customized hybrid constructs with impregnated cells is still in its infancy and many issues related to their structural integrity and the cell functions need to be addressed by research. Meanwhile, it is noticed that nowadays monitoring the success of tissue engineered constructs must rely on animal models, which have to be sacrificed for subsequent examination based on histological techniques. This becomes a critical issue as tissue engineering advances from animal to human studies, thus raising a great need for non-invasive assessments of engineered constructs in situ. To address the aforementioned issues, this research is aimed to (1) develop novel fabrication processes to fabricate hybrid constructs incorporating living cells (hereafter referred as “construct biofabrication”) for cartilage tissue regeneration and (2) develop non-invasive monitoring methods based on synchrotron X-ray imaging techniques for examining cartilage tissue constructs in situ. Based on three-dimensional (3D) printing techniques, novel biofabrication processes were developed to create constructs from synthetic polycaprolactone (PCL) polymer framework and cell-impregnated alginate hydrogel, so as to provide both structural and biological properties as desired in cartilage tissue engineering. To ensure the structural integrity of the constructs, the influence of both PCL polymer and alginate was examined, thus forming a basis to prepare materials for subsequent construct biofabrication. To ensure the biological properties, three types of cells, i.e., two primary cell populations from embryonic chick sternum and an established chondrocyte cell line of ATDC5 were chosen to be incorporated in the construct biofabrication. The biological performance of the cells in the construct were examined along with the influence of the polymer melting temperature on them. The promising results of cell viability and proliferation as well as cartilage matrix production demonstrate that the developed processes are appropriate for fabricating hybrid constructs for cartilage tissue engineering. To develop non-invasive in situ assessment methods for cartilage and other soft tissue engineering applications, synchrotron phase-based X-ray imaging techniques of diffraction enhanced imaging (DEI), analyzer based imaging (ABI), and inline phase contrast imaging (PCI) were investigated, respectively, with samples prepared from pig knees implanted with low density scaffolds. The results from the computed-tomography (CT)-DEI, CT-ABI, and extended-distance CT-PCI showed the scaffold implanted in pig knee cartilage in situ with structural properties more clearly than conventional PCI and clinical MRI, thus providing information and means for tracking the success of scaffolds in tissue repair and remodeling. To optimize the methods for live animal and eventually for human patients, strategies with the aim to reduce the radiation dose during the imaging process were developed by reducing the number of CT projections, region of imaging, and imaging resolution. The results of the developed strategies illustrate that effective dose for CT-DEI, CT-ABI, and extended-distance CT-PCI could be reduced to 0.3-10 mSv, comparable to the dose for clinical X-ray scans, without compromising the image quality. Taken together, synchrotron X-ray imaging techniques were illustrated promising for developing non-invasive monitoring methods for examining cartilage tissue constructs in live animals and eventually in human patients.