Modeling the Anisotropic Resolution and Noise Properties of Digital Breast Tomosynthesis

Digital breast tomosynthesis (DBT) is a 3D imaging modality in which a reconstruction of the breast is generated from various x-ray projections. Due to the newness of this technology, the development of an analytical model of image quality has been on-going. In this thesis, a more complete model is developed by addressing the limitations found in the previous linear systems (LS) model [Zhao, Med. Phys. 2008, 35(12): 5219-32]. A central assumption of the LS model is that the angle of x-ray incidence is approximately normal to the detector in each projection. To model the effect of oblique x-ray incidence, this thesis generalizes Swank\u27s calculations of the transfer functions of x-ray fluorescent screens to arbitrary incident angles. In the LS model, it is also assumed that the pixelation in the reconstruction grid is the same as the detector; hence, the highest frequency that can be resolved is the detector alias frequency. This thesis considers reconstruction grids with smaller pixelation to investigate super-resolution, or visibility of higher frequencies. A sine plate is introduced as a conceptual test object to analyze super-resolution. By orienting the long axis of the sine plate at various angles, the feasibility of oblique reconstruction planes is also investigated. This formulation differs from the LS model in which reconstruction planes are parallel to the breast support. It is shown that the transfer functions for arbitrary angles of x-ray incidence can be modeled in closed form. The high frequency modulation transfer function (MTF) and detective quantum efficiency (DQE) are degraded due to oblique x-ray incidence. In addition, using the sine plate, it is demonstrated that a reconstruction can resolve frequencies exceeding the detector alias frequency. Experimental images of bar patterns verified the existence of super-resolution. Anecdotal clinical examples showed that super-resolution improves the visibility of microcalcifications. The feasibility of oblique reconstructions was established theoretically with the sine plate and was validated experimentally with bar patterns. This thesis develops a more complete model of image quality in DBT by addressing the limitations of the LS model. In future studies, this model can be used as a tool for optimizing DBT

An apodized-aperture x-ray detector design for improved image quality in mammography

X-ray imaging for early cancer detection, such as screening mammography, requires images with high signal-to-noise ratio (SNR) using low levels of radiation exposure. Conventional detectors consist of a matrix of sensor elements, producing images where each pixel corresponds to a single sensor element. This imposes a fundamental limitation on image contrast and SNR for imaging fine detail for a given exposure. The work presented here reconsiders x-ray image formation using a new x-ray detector design that synthesizes image pixels from a large number of very small sensor elements with the goal of optimizing contrast and SNR. Our new detector design, called apodized-aperture pixel (AAP), makes use of recent technology developments to produce images from an “over-sampled” sensor signal while suppressing both signal and noise aliasing to improve the modulation transfer function (MTF) and detective quantum efficiency (DQE). Signal and noise performance of the AAP approach is described theoretically using a cascaded-systems analysis. This approach preserves the MTF of the small sensor elements up to the image sampling cut-off frequency where the MTF is increased by up to 53%. Frequencies above the cut-off are suppressed, eliminating both signal and noise aliasing artifacts and corresponding to a high-frequency DQE increase by 2.5x. X-ray interactions in a scintillator introduce signal and noise correlations, including x-ray reabsorption and converter blur, resulting in reduced aliasing and decreased improvement in DQE. Best results with the AAP design were obtained using a high-resolution converter, such as selenium (Se), with little impact from reabsorption. Implementation on a Se/CMOS micro-sensor prototype with 7.8\mum element size with image pixel size approximately 50\mum showed a flat DQE curve (ideal) up to 10cycles/mm. AAP images of resolution test patterns, mammography phantoms, and specimen imaging of micro-calcifications from biopsies showed the expected improvements in SNR and visibility of fine-detail. It is concluded that synthesizing image pixels from small physical sensor elements can increase MTF and DQE, and eliminate aliasing artifacts, for a desired image pixel size. The resulting increase in SNR may benefit all forms of radiography, and in particular mammography, where accurate visualization of fine detail is important for early cancer detection

Image quality of energy-dependent approaches for x-ray angiography

Digital subtraction angiography (DSA) is an x-ray-based imaging method widely used for diagnosis and treatment of patients with vascular disease. This technique uses subtraction of images acquired before and after injection of an iodinated contrast agent to generate iodine-specific images. While it is extremely successful at imaging structures that are near-stationary over a period of several seconds, motion artifacts can result in poor image quality with uncooperative patients and DSA is rarely used for coronary applications. Alternative methods of generating iodine-specific images with reduced motion artifacts might exploit the energy-dependence of x-ray attenuation in a patient. This could be performed either by aquiring two or more post-injection images at different x-ray energies or from an analysis of the spectral shape of the transmitted spectrum. The first method, which we call energy-subtraction angiography (ESA), was introduced as a dual-energy alternative to DSA over two decades ago but technological limitations of the time resulted in poor image quality. The second potential method, energy-resolved angiography (ERA), requires energy-resolving photon-counting (EPC) x-ray detectors that are under development in a number of laboratories. The goals of this thesis were to: 1) develop a method of comparing image quality in terms of signal-to-noise ratio (SNR) obtained using ESA and ERA with DSA assuming ideal instrumentation for each; 2) develop a method of describing performance and image quality that can be obtained in practice with photon-counting detectors, and; 3) assess the potential of ESA and ERA by comparing the available iodine SNR with that of DSA including the effects of non-ideal detector performance. It is shown that using ideal instrumentation both ESA and ERA can provide iodine-specific images with SNR equal to that of DSA. However, stochastic x-ray interaction and detection processes will degrade SNR obtained with ERA and ESA to a larger extent than DSA. Energy-resolved angiography will achieve near-ideal performance only with low detector electronic noise levels, high collection efficiency of secondary quanta liberated in the detector, and low Compton cross sections. It is concluded that, when these conditions are satsified, ESA and ERA can provide iodine SNR within 25% of that of DSA for the same patient entrance exposure, and therefore may provide alternatives to DSA in situations where motion artifacts are expected to result in compromised DSA procedures, such as in coronary applications. This could have important applications for subtraction imaging of the coronary arteries in the near future

An experimental and theoretical study of the dark current and x-ray sensitivity of amorphous selenium x-ray photoconductors

Recently, the world of diagnostic radiography has seen the integration of digital flat panel x-ray image detectors into x-ray imaging systems, replacing analog film screens. These flat panel x-ray imagers (FPXIs) have been shown to produce high quality x-ray images and provide many advantages that are inherent to a fully digital technology. Direct conversion FPXIs based on a photoconductive layer of stabilized amorphous selenium (a-Se) have been commercialized and have proven particularly effective in the field of mammography. In the operation of these detectors, incident x-ray photons are converted directly to charge carriers in the a-Se layer and drifted to electrodes on either side of the layer by a large applied field (10 V/μm). The applied field causes a dark current to flow which is not due to the incident radiation and this becomes a source of noise which can reduce the dynamic range of the detector. The level of dark current in commercialized detectors has been reduced by the deposition of thin n- and p- type blocking layers between the electrodes and the bulk of the a-Se. Despite recent research into the dark current in metal/a-Se/metal sandwich structures, much is still unknown about the true cause and nature of this phenomenon. The work in this Ph.D. thesis describes an experimental and theoretical study of the dark current in these structures. Experiments have been performed on five separate sets of a-Se samples which approximate the photoconductive layer in an FPXI. The dark current has been measured as a function of time, sample structure, applied field, sample thickness and contact metal used. This work has conclusively shown that the dark current is almost entirely due to the injection of charge carriers from the contacts and the contribution of Poole-Frenkel enhanced bulk thermal generation is negligible. There is also evidence that while the dark current is initially controlled by the injection of holes from the positive contact, several minutes after the application of the bias, the dark current due to hole injection may decay to the point where the electron current becomes significant and even dominant. These conclusions are supported by numerical calculations of the dark current transients which have been calibrated to match experimental results. Work detailed in this Ph.D. thesis also focuses on Monte Carlo modeling of the x-ray sensitivity of a-Se FPXIs. The higher the x-ray sensitivity of a detector, the lower the radiation dose required to acquire an acceptable image. FPXIs can experience a decrease in the x-ray sensitivity of the photoconductive layer with accumulating exposure, leading to a phenomenon known as “ghosting”. Modeling this decrease in sensitivity can uncover the reasons behind it. The Monte Carlo model described in this thesis is a continuation of a previous model which now considers the effects of the n- and p-like blocking layers and the flow of dark current between x-ray exposures. The simulation results explain how deep trapping of photogenerated charge carriers, and the resulting effect on the electric field distribution, contribute to sensitivity loss. The model has shown excellent agreement with experimental data and has accurately predicted a sensitivity recovery once exposure has ceased which is due to primarily to the relaxation of metastable x-ray-induced carrier trap states

On the development of a novel detector for simultaneous imaging and dosimetry in radiotherapy

Radiotherapy uses x-ray beams to deliver prescribed radiation doses that conform to target anatomy and minimise exposure of healthy tissue. Accuracy of dose delivery is essential, thus verification of dose distributions in vivo is desirable to monitor treatments and prevent errors from compromising patient outcomes. Electronic portal imaging devices (EPIDs) are commonly used x-ray imagers, however their non water-equivalent response complicates use for dosimetry. In this thesis, a Monte Carlo (MC) model of a standard EPID was developed and extended to novel water-equivalent configurations based on prototypes in which the high atomic number components were replaced with an array of plastic scintillator fibres. The model verified that full simulation of optical transport is not necessary to predict the standard EPID dose response, which can be accurately quantified from energy deposited in the phosphor screen. By incorporating computed tomography images into the model, its capacity to predict portal dose images of humanoid anatomy was also demonstrated. The prototype EPID’s water-equivalent dose response was characterised experimentally and with the MC model. Despite exhibiting lower spatial resolution and contrast-to-noise ratio relative to the standard EPID, its image quality was sufficient to discern gross anatomical structures of an anthropomorphic phantom. Opportunities to improve imaging performance while maintaining a water-equivalent dose response were identified using the model. Longer fibres increased efficiency and use of an extra-mural absorber maximised spatial resolution. Optical coupling between the scintillator fibres and the imaging panel may further improve performance. This thesis demonstrates the feasibility of developing a next-generation EPID for simultaneous imaging and dosimetry in radiotherapy. Such a detector could monitor treatment deliveries in vivo and thereby facilitate adaptations to treatment plans in order to improve patient outcomes

Digital radiography: image acquisition and scattering reduction in x-ray imaging.

Since the discovery of the X-rays in 1895, their use in both medical and industrial imaging applications has gained increasing importance. As a consequence, X-ray imaging devices have evolved and adapted to the needs of individual applications, leading to the appearance of digital image capture devices. Digital technologies introduced the possibility of separating the image acquisition and image processing steps, allowing their individual optimization. This thesis explores both areas, by seeking the improvement in the design of the new family of Varex Imaging CMOS X-ray detectors and by developing a method to reduce the scatter contribution in mammography examinations using image post-processing techniques. During the CMOS X-ray detector product design phase, it is crucial to detect any short- comings that the detector might present. Image characterization techniques are a very efficient method for finding these possible detector features. This first part of the thesis focused in taking these well-known test methods and adapt and optimize them, so they could act as a red flag indicating when something needed to be investigated. The methods chosen in this study have proven to be very effective in finding detector short- comings and the designs have been optimised in accordance with the results obtained. With the aid of the developed imaging characterization tests, new sensor designs have been successfully integrated into a detector, resulting in the recent release into the market of a new family of Varex Imaging CMOS X-ray detectors. The second part of the thesis focuses in X-ray mammography applications, the gold standard technique in breast cancer screening programmes. Scattered radiation degrades the quality of the image and complicates the diagnosis process. Anti-scatter grids, the main scattering reduction technique, are not a perfect solution. This study is concerned with the use of image post-processing to reduce the scatter contribution in the image, by convolving the output image with kernels obtained from simplified Monte Carlo simulations. The proposed semi-empirical approach uses three thickness-dependant symmetric kernels to accurately estimate the environment contribution to the breast, which has been found to be of key importance in the correction of the breast-edge area. When using a single breast thickness-dependant kernel to convolve the image, the post-processing technique can over-estimate the scattering up to 60%. The method presented in this study reduces the uncertainty to a 4-10% range for a 35 to 70 mm breast thickness range, making it a very efficient scatter modelling technique. The method has been successfully proven against full Monte Carlo simulations and mammography phantoms, where it shows clear improvements in terms of the contrast to noise ratio and variance ratio when the performance is compared against images acquired with anti-scatter grids

On the development of a novel detector for simultaneous imaging and dosimetry in radiotherapy

Radiotherapy uses x-ray beams to deliver prescribed radiation doses that conform to target anatomy and minimise exposure of healthy tissue. Accuracy of dose delivery is essential, thus verification of dose distributions in vivo is desirable to monitor treatments and prevent errors from compromising patient outcomes. Electronic portal imaging devices (EPIDs) are commonly used x-ray imagers, however their non water-equivalent response complicates use for dosimetry. In this thesis, a Monte Carlo (MC) model of a standard EPID was developed and extended to novel water-equivalent configurations based on prototypes in which the high atomic number components were replaced with an array of plastic scintillator fibres. The model verified that full simulation of optical transport is not necessary to predict the standard EPID dose response, which can be accurately quantified from energy deposited in the phosphor screen. By incorporating computed tomography images into the model, its capacity to predict portal dose images of humanoid anatomy was also demonstrated. The prototype EPID’s water-equivalent dose response was characterised experimentally and with the MC model. Despite exhibiting lower spatial resolution and contrast-to-noise ratio relative to the standard EPID, its image quality was sufficient to discern gross anatomical structures of an anthropomorphic phantom. Opportunities to improve imaging performance while maintaining a water-equivalent dose response were identified using the model. Longer fibres increased efficiency and use of an extra-mural absorber maximised spatial resolution. Optical coupling between the scintillator fibres and the imaging panel may further improve performance. This thesis demonstrates the feasibility of developing a next-generation EPID for simultaneous imaging and dosimetry in radiotherapy. Such a detector could monitor treatment deliveries in vivo and thereby facilitate adaptations to treatment plans in order to improve patient outcomes

Contributions to the improvement of image quality in CBCT and CBμCT and application in the development of a CBμCT system

During the last years cone-beam x-ray CT (CBCT) has been established as a widespread imaging technique and a feasible alternative to conventional CT for dedicated imaging tasks for which the limited flexibility offered by conventional CT advises the development of dedicated designs. CBCT systems are starting to be routinely used in image guided radiotherapy; image guided surgery using C-arms; scan of body parts such as the sinuses, the breast or extremities; and, especially, in preclinical small-animal imaging, often coupled to molecular imaging systems. Despite the research efforts advocated to the advance of CBCT, the challenges introduced by the use of large cone angles and two-dimensional detectors are a field of vigorous research towards the improvement of CBCT image quality. Moreover, systems for small-animal imaging add to the challenges posed by clinical CBCT the need of higher resolution to obtain equivalent image quality in much smaller subjects. This thesis contributes to the progress of CBCT imaging by addressing a variety of issues affecting image quality in CBCT in general and in CBCT for small-animal imaging (CBμCT). As part of this work we have assessed and optimized the performance of CBμCT systems for different imaging tasks. To this end, we have developed a new CBμCT system with variable geometry and all the required software tools for acquisition, calibration and reconstruction. The system served as a tool for the optimization of the imaging process and for the study of image degradation effects in CBμCT, as well as a platform for biological research using small animals. The set of tools for the accurate study of CBCT was completed by developing a fast Monte Carlo simulation engine based on GPUs, specifically devoted to the realistic estimation of scatter and its effects on image quality in arbitrary CBCT configurations, with arbitrary spectra, detector response, and antiscatter grids. This new Monte Carlo engine outperformed current simulation platforms by more than an order of magnitude. Due to the limited options for simulation of spectra in microfocus x-ray sources used in CBμCT, we contributed in this thesis a new spectra generation model based on an empirical model for conventional radiology and mammography sources modified in accordance to experimental data. The new spectral model showed good agreement with experimental exposure and attenuation data for different materials. The developed tools for CBμCT research were used for the study of detector performance in terms of dynamic range. The dynamic range of the detector was characterized together with its effect on image quality. As a result, a new simple method for the extension of the dynamic range of flat-panel detectors was proposed and evaluated. The method is based on a modified acquisition process and a mathematical treatment of the acquired data. Scatter is usually identified as one of the major causes of image quality degradation in CBCT. For this reason the developed Monte Carlo engine was applied to the in-depth study of the effects of scatter for a representative range of CBCT embodiments used in the clinical and preclinical practice. We estimated the amount and spatial distribution of the total scatter fluence and the individual components within. The effect of antiscatter grids in improving image quality and in noise was also evaluated. We found a close relation between scatter and the air gap of the system, in line with previous results in the literature. We also observed a non-negligible contribution of forward-directed scatter that is responsible to a great extent for streak artifacts in CBCT. The spatial distribution of scatter was significantly affected by forward scatter, somewhat challenging the usual assumption that the scatter distribution mostly contains low-frequencies. Antiscatter grids showed to be effective for the reduction of cupping, but they showed a much lower performance when dealing with streaks and a shift toward high frequencies of the scatter distributions. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------A lo largo de los últimos años, el TAC de rayos X de haz cónico (CBCT, de “conebeam” CT) se ha posicionado como una de las técnicas de imagen más ampliamente usadas. El CBCT se ha convertido en una alternativa factible al TAC convencional en tareas de imagen específicas para las que la flexibilidad limitada ofrecida por este hace recomendable el desarrollo de sistemas de imagen dedicados. De esta forma, el CBCT está empezando a usarse de forma rutinaria en varios campos entre los que se incluyen la radioterapia guiada por imagen, la cirugía guiada por imagen usando arcos en C, imagen de partes de la anatomía en las que el TAC convencional no es apropiado, como los senos nasales, las extremidades o la mama, y, especialmente el campo de imagen preclínica con pequeño animal. Los sistemas CBCT usados en este último campo se encuentran habitualmente combinados con sistemas de imagen molecular. A pesar del trabajo de investigación dedicado al avance de la técnica CBCT en los últimos años, los retos introducidos por el uso de haces cónicos y de detectores bidimensionales son un campo candente para la investigación médica, con el objetivo de obtener una calidad de imagen equivalente o superior a la proporcionada por el TAC convencional. En el caso de imagen preclínica, a los retos generados por el uso de CBCT se une la necesidad de una mayor resolución de imagen que permita observar estructuras anatómicas con el mismo nivel de detalle obtenido para humanos. Esta tesis contribuye al progreso del CBCT mediante el estudio de usa serie de efectos que afectan a la calidad de imagen de CBCT en general y en el ámbito preclínico en particular. Como parte de este trabajo, hemos evaluado y optimizado el rendimiento de sistemas CBCT preclínicos en función de la tarea de imagen concreta. Con este fin se ha desarrollado un sistema CBCT para pequeños animales con geometría variable y todas las herramientas necesarias para la adquisición, calibración y reconstrucción de imagen. El sistema sirve como base para la optimización de protocolos de adquisición y para el estudio de fuentes de degradación de imagen además de constituir una plataforma para la investigación biológica en pequeño animal. El conjunto de herramientas para el estudio del CBCT se completó con el desarrollo de una plataforma acelerada de simulación Monte Carlo basada en GPUs, optimizada para la estimación de radiación dispersa en CBCT y sus efectos en la calidad de imagen. La plataforma desarrollada supera el rendimiento de las actuales en más de un orden de magnitud y permite la inclusión de espectros policromáticos de rayos X, de la respuesta realista del detector y de rejillas antiscatter. Debido a las escasas opciones ofrecidas por la literatura para la estimación de espectros de rayos X para fuentes microfoco usadas en imagen preclínica, en esta tesis se incluye el desarrollo de un nuevo modelo de generación de espectros, basado en un modelo existente para fuentes usadas en radiología y mamografía. El modelo fue modificado a partir de datos experimentales. La precisión del modelo presentado se comprobó mediante datos experimentales de exposición y atenuación para varios materiales. Las herramientas desarrolladas se usaron para estudiar el rendimiento de detectores de rayos tipo flat-panel en términos de rango dinámico, explorando los límites impuestos por el mismo en la calidad de imagen. Como resultado se propuso y evaluó un método para la extensión del rango dinámico de este tipo de detectores. El método se basa en la modificación del proceso de adquisición de imagen y en una etapa de postproceso de los datos adquiridos. El simulador Monte Carlo se empleó para el estudio detallado de la naturaleza, distribución espacial y efectos de la radiación dispersa en un rango de sistemas CBCT que cubre el espectro de aplicaciones propuestas en el entorno clínico y preclínico. Durante el estudio se inspeccionó la cantidad y distribución espacial de radiación dispersa y de sus componentes individuales y el efecto causado por la inclusión de rejillas antiscatter en términos de mejora de calidad de imagen y de ruido en la imagen. La distribución de radiación dispersa mostró una acentuada relación con la distancia entre muestra y detector en el equipo, en línea con resultados publicados previamente por otros autores. También se encontró una influencia no despreciable de componentes de radiación dispersa con bajos ángulos de desviación, poniendo en tela de juicio la tradicional asunción que considera que la distribución espacial de la radiación dispersa está formada casi exclusivamente por componentes de muy baja frecuencia. Las rejillas antiscatter demostraron ser efectivas para la reducción del artefacto de cupping, pero su efectividad para tratar artefactos en forma de línea (principalmente formados por radiación dispersa con bajo ángulo de desviación) resultó mucho menor. La inclusión de estas rejillas también enfatiza las componentes de alta frecuencia de la distribución espacial de la radiación dispersa