System Characterizations and Optimized Reconstruction Methods for Novel X-ray Imaging

In the past decade there have been many new emerging X-ray based imaging technologies developed for different diagnostic purposes or imaging tasks. However, there exist one or more specific problems that prevent them from being effectively or efficiently employed. In this dissertation, four different novel X-ray based imaging technologies are discussed, including propagation-based phase-contrast (PB-XPC) tomosynthesis, differential X-ray phase-contrast tomography (D-XPCT), projection-based dual-energy computed radiography (DECR), and tetrahedron beam computed tomography (TBCT). System characteristics are analyzed or optimized reconstruction methods are proposed for these imaging modalities. In the first part, we investigated the unique properties of propagation-based phase-contrast imaging technique when combined with the X-ray tomosynthesis. Fourier slice theorem implies that the high frequency components collected in the tomosynthesis data can be more reliably reconstructed. It is observed that the fringes or boundary enhancement introduced by the phase-contrast effects can serve as an accurate indicator of the true depth position in the tomosynthesis in-plane image. In the second part, we derived a sub-space framework to reconstruct images from few-view D-XPCT data set. By introducing a proper mask, the high frequency contents of the image can be theoretically preserved in a certain region of interest. A two-step reconstruction strategy is developed to mitigate the risk of subtle structures being oversmoothed when the commonly used total-variation regularization is employed in the conventional iterative framework. In the thirt part, we proposed a practical method to improve the quantitative accuracy of the projection-based dual-energy material decomposition. It is demonstrated that applying a total-projection-length constraint along with the dual-energy measurements can achieve a stabilized numerical solution of the decomposition problem, thus overcoming the disadvantages of the conventional approach that was extremely sensitive to noise corruption. In the final part, we described the modified filtered backprojection and iterative image reconstruction algorithms specifically developed for TBCT. Special parallelization strategies are designed to facilitate the use of GPU computing, showing demonstrated capability of producing high quality reconstructed volumetric images with a super fast computational speed. For all the investigations mentioned above, both simulation and experimental studies have been conducted to demonstrate the feasibility and effectiveness of the proposed methodologies

Implementation of Digital Tomosynthesis in a Real Radiology System

The work included in this thesis is framed on one of the lines of research carried out by the Biomedical Imaging and Instrumentation Group from the Bioengineering and Aerospace Department of Universidad Carlos III de Madrid working jointly with the Gregorio Marañón Hospital. Its goal is to design and develop a new generation of Radiology Systems, valid for clinical and veterinary applications, through the research and development of innovative technologies in advanced image processing oriented to increase image quality, to reduce dose and to incorporate tomographic capabilities. The latter will allow bringing tomography to situations in which a CT system is not allowable due to cost issues or when the patient cannot be moved (for instance, during surgery or ICU). It may also be relevant to reduce the radiation dose delivered to the patient, if we can obtain a tomographic image from fewer projections than using a CT. In that context, this thesis deals with incorporating pseudo-tomographic capabilities, through a tomosynthesis protocol, in a radiology room originally designed for planar images: the NOVA FA digital radiography system developed by SEDECAL. The room consists of an X-ray generator, a vertical wall stand system, a mobile elevating table and an automatic ceiling suspension which allows the X-ray source to cover the whole volume of the room. Images are acquired using a flat panel detector connected through Wi-Fi to the computer station. Having evolved from conventional tomography, tomosynthesis produces section images at any depth from projections obtained at different angles along a linear sweep through the use of a suitable reconstruction algorithm. A workflow was established for the incorporation of tomosynthesis protocols to the NOVA FA system starting from the design of the protocol down to the reconstruction step. This required the understanding of the system and the development of several software tools. For the design of new protocols, a tomosynthesis module was incorporated to an in-house X- ray simulation tool programmed in Matlab and CUDA. As the X-ray room was built specifically for research, everything is manual and all the software is open. This system is designed only for planar radiography and, as a consequence, it is very cumbersome to incorporate a protocol that involves more than one projection. Therefore, a new software tool was implemented in Matlab that allows the translation of each of the source-detector positions corresponding to the tomosynthesis design to the geometrical parameters of the NOVA FA system and their automatic addition to its database. To obtain a tomographic image from the data acquire, a reconstruction tool was developed in Matlab with the ability to use several reconstruction algorithms including Shift-and-Add and Backprojection. Finally, two different evaluations were conducted: a geometric evaluation to assess the correlation between the simulation tool and the X-ray room and an evaluation of the complete workflow through the design and implementation of a simple tomosynthesis protocol using a PBU-50 body phantom developed by Kyoto Kagatu. The results of these evaluation studies showed the feasibility of the proposal. It should be noted that the work of this thesis has a clear application in industry, since it is part of a proof of concept of the new generation of radiology systems which will be commercialised worldwide by the company SEDECAL.Ingeniería Biomédic

Endorectal Digital Prostate Tomosynthesis

Several areas of prostate cancer (PCa) management, such as imaging permanent brachytherapy implants or small, aggressive lesions, benefit from high image resolution. Current PCa imaging methods can have inadequate resolution for imaging these areas. Endorectal digital prostate tomosynthesis (endoDPT), an imaging method that combines an external x-ray source and an endorectal x-ray sensor, can produce three-dimensional images of the prostate region that have high image resolution compared to typical methods. This high resolution may improve PCa management and increase positive outcomes in affected men. This dissertation presents the initial development of endoDPT, including system design, image quality assessment, and examples of possible applications to prostate imaging. Experiments using computational phantoms, physical phantoms, and canine prostate specimens were conducted. Initial system design was performed computationally and three methods of endoDPT image reconstruction were developed: shift and add (SAA), backprojection (BP), and filtered BP (FBP). A physical system was developed using an XDR intraoral x-ray sensor and a GE radiography unit. The resolution and radiation dose of endoDPT were measured and compared to a GE CT scanner. Canine prostate specimens that approximated clinical cases of PCa management were imaged and compared using endoDPT, the above CT scanner, and a GE MRI scanner. This study found that the resolution of endoDPT was significantly higher than CT. The radiation dose of endoDPT was significantly lower than CT in the regions of the phantom that were not in the endoDPT field of view (FoV). Inside the endoDPT FoV, the radiation dose ranged from significantly less than to significantly greater than CT. The endoDPT images of the canine prostate specimens demonstrated qualitative improvements in resolution compared to CT and MRI, but endoDPT had difficulty in visualizing larger structures, such as the prostate border. Overall, this study has demonstrated endoDPT has high image resolution compared to typical methods of PCa imaging. Future work will be focused on development of a prototype system that improves scanning efficiency that can be used to optimize endoDPT and perform pre-clinical studies

Digital Tomosynthesis as a Problem-Solving Technique to Confirm or Exclude Pulmonary Lesions in Hidden Areas of the Chest

Objectives: To evaluate the capability of digital tomosynthesis (DTS) to characterize suspected pulmonary lesions in the so-called hidden areas at chest X-ray (CXR). Materials and Methods: Among 726 patients with suspected pulmonary lesions at CXR who underwent DTS, 353 patients (201 males, 152 females; age 71.5   10.4 years) revealed suspected pulmonary lesions in the apical, hilar, retrocardiac, or paradiaphragmatic lung zones and were retrospectively included. Two readers analyzed CXR and DTS images and provided a confidence score: 1 or 2 = definitely or probably benign pulmonary or extra-pulmonary lesion, or pulmonary pseudo-lesion deserving no further diagnostic work-up; 3 = indeterminate lesion; 4 or 5 = probably or definitely pulmonary lesion deserving further diagnostic work-up by CT. The nature of DTS findings was proven by CT (n = 108) or CXR during follow-up (n = 245). Results: In 62/353 patients the suspected lung lesions were located in the lung apex, in 92/353 in the hilar region, in 59/353 in the retrocardiac region, and in 140/353 in the paradiaphragmatic region. DTS correctly characterized the CXR findings as benign pulmonary or extrapulmonary lesion (score 1 or 2) in 43/62 patients (69%) in the lung apex region, in 56/92 (61%) in the pulmonary hilar region, in 40/59 (67%) in the retrocardiac region, and in 106/140 (76%) in the paradiaphragmatic region, while correctly recommending CT in the remaining cases due to the presence of true solid pulmonary lesion, with the exception of 22 false negative findings (60 false positive findings). DTS showed a significantly (p < 0.05) increased sensitivity, specificity, and overall diagnostic accuracy and area under ROC curve compared to CXR alone. Conclusions: DTS allowed confirmation or exclusion of the presence of true pulmonary lesions in the hidden areas of the chest

STATIONARY DIGITAL TOMOSYNTHESIS: IMPLEMENTATION, CHARACTERIZATION, AND IMAGE PROCESSING TECHNIQUES

The use of carbon nanotube cathodes for x-ray generation was pioneered and perfected by our team in the Applied Nanotechnology Laboratory at the University of North Carolina at Chapel Hill. Over the past decade, carbon nanotube (CNT) field emission x-ray source technology has matured and translated into multiple pre-clinical and clinical devices. One of the most prominent implementations of CNT x-ray technology is a limited angle tomography method called tomosynthesis, which is rapidly emerging in clinical radiography. The purpose of this project is two-fold, to develop and characterize to the latest iteration, stationary intraoral tomosynthesis, and develop a low-dose, effective scatter reduction technique for breast and chest tomosynthesis. The first portion of this project was to develop and evaluate a new quasi-3D imaging modality for dental imaging. My work consists of experiments which dictated the design parameters and subsequent system evaluation of the dedicated s-IOT clinical prototype system currently installed in the UNC Department of Oral and Maxillofacial Radiology clinic in the School of Dentistry. Experiments were performed in our lab to determine optimal source array geometry and system configuration. The system was fabricated by our commercial partner then housed in our research lab where I performed initial characterization and assisted with software development. After installation in the SOD, I performed additional system characterization, including source output validation, dosimetry, and quantification of resolution. The system components and software were refined through a rapid feedback loop with the engineers involved. Four pre-clinical imaging studies have been performed in collaboration with several dentists using phantoms, extracted teeth, and cadaveric dentition. I have generated an operating manual and trained four dental radiologists in the use of the s-IOT device. The system has now been vetted and is ready for patient use. The second portion of this project consists of hardware development and implementation of an image processing technique for scatter correction. The primary sampling scatter correction (PSSC) is a beam pass technique to measure the primary transmission through the patient and calculate the scatter profile for subtraction. Though developed for breast and chest tomosynthesis, utilization in mammography and chest radiography are also demonstrated in this project. This dissertation is composed of five chapters. Chapters one and two provide the basics of x-ray generation and a brief history of the evolution of carbon nanotube x-ray source technology in our lab at UNC. Chapter three focuses on stationary intraoral tomosynthesis. The first section provides background information on dental radiology and project motivation. Sections 3.2 and 3.3 detail my work in benchtop feasibility and optimization studies, as well as characterization and evaluation of the clinical prototype. Chapter four introduces scatter in imaging, providing motivation for my work on primary sampling scatter correction (PSSC) image processing method, detailed in chapter five.Doctor of Philosoph

Digital chest radiography: an update on modern technology, dose containment and control of image quality

The introduction of digital radiography not only has revolutionized communication between radiologists and clinicians, but also has improved image quality and allowed for further reduction of patient exposure. However, digital radiography also poses risks, such as unnoticed increases in patient dose and suboptimum image processing that may lead to suppression of diagnostic information. Advanced processing techniques, such as temporal subtraction, dual-energy subtraction and computer-aided detection (CAD) will play an increasing role in the future and are all targeted to decrease the influence of distracting anatomic background structures and to ease the detection of focal and subtle lesions. This review summarizes the most recent technical developments with regard to new detector techniques, options for dose reduction and optimized image processing. It explains the meaning of the exposure indicator or the dose reference level as tools for the radiologist to control the dose. It also provides an overview over the multitude of studies conducted in recent years to evaluate the options of these new developments to realize the principle of ALARA. The focus of the review is hereby on adult applications, the relationship between dose and image quality and the differences between the various detector systems

Iterative CT reconstruction from few projections for the nondestructive post irradiation examination of nuclear fuel assemblies

The core components (e.g. fuel assemblies, spacer grids, control rods) of the nuclear reactors encounter harsh environment due to high temperature, physical stress, and a tremendous level of radiation. The integrity of these elements is crucial for safe operation of the nuclear power plants. The Post Irradiation Examination (PIE) can reveal information about the integrity of the elements during normal operations and off‐normal events. Computed tomography (CT) is a tool for evaluating the structural integrity of elements non-destructively. CT requires many projections to be acquired from different view angles after which a mathematical algorithm is adopted for reconstruction. Obtaining many projections is laborious and expensive in nuclear industries. Reconstructions from a small number of projections are explored to achieve faster and cost-efficient PIE. Classical reconstruction algorithms (e.g. filtered back projection) cannot offer stable reconstructions from few projections and create severe streaking artifacts. In this thesis, conventional algorithms are reviewed, and new algorithms are developed for reconstructions of the nuclear fuel assemblies using few projections. CT reconstruction from few projections falls into two categories: the sparse-view CT and the limited-angle CT or tomosynthesis. Iterative reconstruction algorithms are developed for both cases in the field of compressed sensing (CS). The performance of the algorithms is assessed using simulated projections and validated through real projections. The thesis also describes the systematic strategy towards establishing the conditions of reconstructions and finds the optimal imaging parameters for reconstructions of the fuel assemblies from few projections. --Abstract, page iii

Advanced capabilities for planar X-ray systems

Mención Internacional en el título de doctorThe past decades have seen a rapid evolution towards the use of digital detectors in radiology and a more flexible robotized movement of the system components, X-ray tube and detector. This evolution opened the possibility for incorporating advanced capabilities in these planar X-ray systems, and for providing new valuable diagnostic information compared to the previous technology. Some of the current challenges for radiography are to obtain more quantitative images and to reduce the inherent superposition of tissues because of the 2D nature of the technique. Dual energy radiography, based on the acquisition of two images at different source voltages, enables a separate characterization of soft tissue and bone structures. Its benefits over conventional radiography have been proven in different applications, since it improves information content without adding significant extra acquisition time or radiation dose. In a different direction, a really disruptive advance would be to obtain 3D imaging with systems designed just for planar images. The incorporation of tomographic capabilities into these systems would have to deal with the acquisition of a limited number of projections, with non-standard geometrical configurations. This thesis presents original contributions in these two directions: dual energy radiography and 3D imaging with X-ray systems designed for planar imaging. The work is framed in a line of research of the Biomedical Imaging and Instrumentation Group from the Bioengineering and Aerospace Department of University Carlos III de Madrid working jointly with the University Hospital Gregorio Marañón, focused on the advance of radiology systems. This research line is carried out in collaboration with the group of Computer Architecture, Communications and Systems (ARCOS), from the same university, the Imaging Research Laboratory (IRL) of the University of Washington and the research center CREATIS, France. The research has a clear focus on technology transfer to the industry through the company Sedecal, a Spanish multinational among the 10 best world companies in the medical imaging field. The first contribution of this thesis is a complete novel protocol to incorporate dual energy capabilities that enable quantitative planar studies. The proposal is based on the use of a preliminary calibration with a very simple and low-cost phantom formed by two parts that represent soft tissue and bone equivalent materials. This calibration is performed automatically with no strict placement requirements. Compared to current Dual-energy X-ray Absorptiometry (DXA) systems, 1) it provides real mass-thickness values directly, enabling quantitative planar studies instead of relative comparisons, and 2) it is based on an automatic preliminary calibration without the need of interaction of an experienced technician. The second contribution is a novel protocol for the incorporation of tomographic capabilities into X-ray systems originally intended for planar imaging. For this purpose, we faced three main challenges. First, the geometrical trajectory of equipment follows non-standard circular orbits, thus posing severe difficulties for reconstruction. To handle this, the proposed protocol comprises a new geometrical calibration procedure that estimates all the system parameters per-projection. Second, the reconstruction of a limited number of projections from a reduced angular span leads to severe artifacts when using conventional reconstruction methods. To deal with these limited-view data, the protocol includes a novel advanced reconstruction method that incorporates the surface information of the sample, which can be extracted with a 3D light surface scanner. These data are introduced as an imposed constraint following the Split Bregman formulation. The restriction of the search space by exploiting the surface-based support becomes crucial for a complete recovery of the external contour of the sample and surroundings when the angular span is extremely reduced. The modular, efficient and flexible design followed for its implementation allows for the reconstruction of limited-view data with non-standard trajectories. Third, the optimization of the acquisition protocols has not yet explored with these systems. This thesis includes a study of the optimum acquisition protocols that allowed us to identify the possibilities and limitations of these planar systems. Using the surface-constrained method, it is possible to reduce the total number of projections up to 33% and the angular span down to 60 degrees. The contributions of this thesis open the way to provide depth and quantitative information very valuable for the improvement of radiological diagnosis. This could impact considerably the clinical practice, where conventional radiology is still the imaging modality most used, accounting for 80-90% of the total medical imaging exams. These advances open the possibility of new clinical applications in scenarios where 1) the reduction of the radiation dose is key, such as lung cancer screening or Pediatrics, according to the ALARA criteria (As Low As Reasonably Achievable), 2) a CT system is not usable due to movement limitations, such as during surgery or in an ICU and 3) where costs issues complicate the availability of CT systems, such as rural areas or underdeveloped countries. The results of this thesis has a clear application in the industry, since it is part of a proof of concept of the new generation of planar X-ray systems that will be commercialized worldwide by the company SEDECAL (Madrid, Spain).Los últimos años están viendo un rápido avance de los sistemas de radiología hacia el uso de detectores digitales y a una mayor flexibilidad de movimientos de los principales componentes del sistema, el tubo de rayos X y el detector. Esta evolución abre la posibilidad de incorporar capacidades avanzadas en sistemas de imagen plana por rayos X proporcionando nueva información valiosa para el diagnóstico. Dos retos en radiografía son obtener imágenes cuantitativas y reducir la superposición de tejidos debida a la naturaleza proyectiva de la técnica. La radiografía de energía dual, basada en la adquisición de dos imágenes a diferente kilovoltaje, permite obtener imágenes de tejido blando y hueso por separado. Los beneficios de esta técnica que aumenta la cantidad de información sin añadir un tiempo de adquisición o de dosis de radiación extra significativos frente al uso de radiografía convencional, han sido demostrados en diferentes aplicaciones. En otra dirección, un avance realmente disruptivo sería la obtención de imagen 3D con sistemas diseñados únicamente para imagen plana. La incorporación de capacidades tomográficas en estos sistemas tendría que lidiar con la adquisición de un número limitado de proyecciones siguiendo trayectorias no estándar. Esta tesis presenta contribuciones originales en esas dos direcciones: radiografía de energía dual e imagen 3D con sistemas de rayos X diseñados para imagen plana. El trabajo se encuadra en una línea de investigación del grupo de Imagen Biomédica e Instrumentación del Departamento de Bioingeniería e Ingeniería Aerospacial de la Universidad Carlos III de Madrid junto con el Hospital Universitario Gregorio Marañon, centrada en el avance de sistemas de radiología. Esta línea de investigación se desarollada en colaboración con el grupo Computer Architecture, Communications and Systems (ARCOS), de la misma universidad, el grupo Imaging Research Laboratory (IRL) de la Universidad de Washington y el centro de investigación CREATIS, de Francia. Se trata de una línea de investigación con un claro enfoque de transferencia tecnológica a la industria a través de la compañía SEDECAL, una multinacional española de entre las 10 líderes del mundo en el campo de la radiología. La primera contribución de esta tesis es un protocolo completo para incorporar capacidades de energía dual que permitan estudios cuantitativos de imagen plana. La propuesta se basa en una calibración previa con un maniquí simple y de bajo coste formado por dos materiales equivalentes de tejido blando y hueso respectivamente. Comparado con los sistemas actuales DXA (Dual-energy X-ray Absorptiometry), 1) proporciona valores reales de tejido atravesado, 2) se basa en una calibración automática que no requiere la interacción de un técnico con gran experiencia. La segunda contribución es un protocolo nuevo para la incorporación de capacidades tomográficas en sistemas de rayos X originariamente diseñados para imagen plana. Para ello, nos enfrentamos a tres principales dificultades. En primer lugar, las trayectorias que pueden seguir la fuente y el detector en estos sistemas no constituyen órbitas circulares estándares, lo que plantea retos importantes en la caracterización geométrica. Para solventarlo, el protocolo propuesto incluye una calibración geométrica que estima todos los parámetros geométricos del sistema para cada proyección. En segundo lugar, la reconstrucción de un número limitado de proyecciones adquiridas en un rango angular reducido da lugar a artefactos graves cuando se reconstruye con algoritmos convencionales. Para lidiar con estos datos de ángulo limitado, el protocolo incluye un nuevo método avanzado de reconstrucción que incorpora la información de superficie de la muestra, que se puede se obtener con un escáner 3D. Esta información se impone como una restricción siguiendo la formulación de Split Bregman, para compensar la falta de datos. La restricción del espacio de búsqueda a través de la explotación del soporte basado en superficie, es crucial para una recuperación completa del contorno externo de la muestra cuando el rango angular es extremadamente pequeño. El diseño modular, eficiente y flexible de la implementación propuesta permite reconstruir datos de ángulo limitado obtenidos con posiciones de fuente y detector no estándar. En tercer lugar, hasta la fecha, no se ha explorado la optimización del protocolo de adquisición con estos sistemas. Esta tesis incluye un estudio de los protocolos óptimos de adquisición que permitió identificar las posibilidades y limitaciones de estos sistemas de imagen plana. Gracias al método de reconstrucción basado en superficie, es posible reducir el número total de proyecciones hasta el 33% y el rango angular hasta 60 grados. Las contribuciones de esta tesis abren la posibilidad de proporcionar información de profundidad y cuantitativa muy valiosa para la mejora del diagnóstico radiológico. Esto podría impactar considerablemente en la práctica clínica, donde la radiología convencional es todavía la modalidad de imagen más utilizada, abarcando el 80- 90% del total de los exámenes de imagen médica. Estos avances abren la posibilidad de nuevas aplicaciones clínicas en escenarios donde 1) la reducción de la dosis de radiación es clave, como en screening de cáncer de pulmón, de acuerdo con el criterio ALARA (As Low As Reasonably Achievable), 2) no se puede usar un sistema TAC por limitaciones de movimiento como en cirugía o UCI, o 3) el coste limita la disponibilidad de sistemas TAC, como en zonas rurales o en países subdesarrollados. Los resultados de esta tesis presentan una clara aplicación industrial, ya que son parte de un prototipo de la nueva generación de sistemas planos de rayos X que serán distribuidos mundialmente por la compañía SEDECAL.This thesis has been developed as part of several research projects with public funding: - DPI2016-79075-R. ”Nuevos escenarios de tomografía por rayos X”, IP: Mónica Abella García, Ministerio de Economía y Competitividad, 01/01/2017-31/12/2019, 147.620 e. - ”Nuevos escenarios de tomografía por rayos X (NEXT) DPI2016-79075-R. Ministerio de Economía”, Industria y Competitividad. (Universidad Carlos III de Madrid). 30/12/2016-29/12/2019. 147.620 e. (…) - FP7-IMI-2012 (GA-115337), ”PreDict-TB: Model-based preclinical development of anti-tuberculosis drug combinations”. FP7-IMI - Seventh Framework Programme (EC-EFPIA). Unión Europea. (Universidad Carlos III de Madrid). 01/05/2012-31/10/2017. (…) - TEC2013-47270-R, ”Avances en Imagen Radiológica (AIR)”, Ministerio de Economía y Competitividad”, 01/01/2014-31/12/2016. IP: Mónica Abella Garcia and Manuel Desco Menéndez. 160.204 e (…) - RTC-2014-3028-1, ”Nuevos Escenarios Clínicos con Radiología Avanzada (NECRA)”, Ministerio de Economía y Competitividad, 01/06/2014-31/12/2016 IP: Mónica Abella García. 2014-2016. 219.458,96 e - IDI-20130301, ”Nuevo sistema integral de radiografía (INNPROVE: INNovative image PROcessing in medicine and VEterinary)”, IP: Mónica Abella García and Manuel Desco Menéndez. Ministerio de Economía y Competitividad. Subcontratación CDTI, 14/01/2013-31/03/2015. Total: 1.860.629e (UC3M: 325.000e). (Art. 83) - IPT-2012-0401-300000 INNPACTO 2012, ”Tecnologías para Procedimientos Intraoperatorios Seguros y Precisos. XIORT. MINECO. (Universidad Carlos III de Madrid). 01/01/2013-31/12/2015.Programa Oficial de Doctorado en Ingeniería MatemáticaPresidente: Doménec Ros Puig.- Secretario: Cyril Riddell.- Vocal: Yannick Boursie