Design and characterization of advanced diffractive devices for imaging and spectroscopy

Due to the ever-increasing demands of highly integrated optical devices in imaging, spectroscopy, communications, and so on, there is a compelling need to design and characterize novel compact photonic components. The traditional approaches to realizing compact optical devices typically result in large footprints and sizable optical thicknesses. Moreover, they offer few degrees of freedom (DOF), hampering on-demand functionalities, on-chip integration, and scalability. This thesis will address the design and development of ultracompact diffractive devices for imaging and spectroscopy, utilizing advanced machine learning techniques and optimization algorithms. I first present the inverse design of ultracompact dual-focusing lenses and broad-band focusing spectrometers based on adaptive diffractive optical networks (a-DONs), which combine optical diffraction physics and deep learning capabilities for the inverse design of multi-layered diffractive devices. I designed two-layer diffractive devices that can selectively focus incident radiation over well-separated spectral bands at desired distances and also optimized a-DON-based focusing spectrometers with engineered angular dispersion for desired bandwidth and nanometer spectral resolution. Furthermore, I introduced a new approach based on a-DONs for the engineering of diffractive devices with arbitrary k-space, which produces improved imaging performances compared to contour-PSF approaches to lens-less computational imaging. Moreover, my method enables control of sparsity and isotropic k-space in pixelated screens of dielectric scatterers that are compatible with large-scale photolithographic fabrication techniques. Finally, by combining adjoint optimization with the rigorous generalized Mie theory, I developed and characterize functionalized compact devices, which I called "photonic patches," consisting of ~100 dielectric nanocylinders that achieve predefined functionalities such as beam steering, Fresnel zone focusing, local density of states (LDOS) enhancement, etc. My method enables the inverse design of ultracompact focusing spectrometers for on-chip planar integration. Leveraging multiple scattering of light in disordered random media, I additionally demonstrated a novel approach to on-chip spectroscopy driven by high-throughput multifractal (i.e., multiscale) media, resulting in sub-nanometer spectral resolution at the 50×50 µm²-scale footprint

A multi-technique hierarchical X-ray phase-based approach for the characterization and quantification of the effects of novel radiotherapies

Cancer is the first or second leading cause of premature deaths worldwide with an overall rapidly growing burden. Standard cancer therapies include surgery, chemotherapy and radiotherapy (RT) and often a combination of the three is applied to improve the probability of tumour control. Standard therapy protocols have been established for many types of cancers and new approaches are under study especially for treating radio-resistant tumours associated to an overall poor prognosis, as for brain and lung cancers. Follow up techniques able to monitor and investigate the effects of therapies are important for surveying the efficacy of conventionally applied treatments and are key for accessing the curing capabilities and the onset of acute and late adverse effects of new therapies. In this framework, this doctoral Thesis proposes the X-ray Phase Contrast Im-aging - Computed Tomography (XPCI-CT) technique as an imaging-based tool to study and quantify the effects of novel RTs, namely Microbeam and Minibeam Radiation therapy (MRT and MB), and to compare them to the standard Broad Beam (BB) induced effects on brain and lungs. MRT and MB are novel radiotherapies that deliver an array of spatially fractionated X-ray beamlets issued from a synchrotron radiation source, with widths of tens or hundreds of micrometres, respectively. MRT and MB exploit the so-called dose-volume effect: hundreds of Grays are well tolerated by healthy tissues and show a preferential effect on tumour cells and vasculature when delivered in a micrometric sized micro-plane, while induce lethal effects if applied over larger uniform irradiation fields. Such highly collimated X-ray beams need a high-resolution and a full-organ approach that can visualize, with high sensitivity, the effects of the treatment along and outside the beamlets path. XPCI-CT is here suggested and proven as a powerful imaging technique able to determine and quantify the effects of the radiation on normal and tumour-bearing tissues. Moreover, it is shown as an effective technique to complement, with 3D information, the histology findings in the follow-up of the RT treatments. Using a multi-scale and multi-technique X-ray-based approach, I have visualized and analysed the effects of RT delivery on healthy and glioblastoma multiforme (GBM)-bearing rat brains as well as on healthy rat lungs. Ex-vivo XPCI-CT datasets acquired with isotropic voxel sizes in the range 3.253 – 0.653 μm3 could distinguish, with high sensitivity, the idiopathic effects of MRT, MB and BB therapies. Histology, immunohistochemistry, Small- and Wide-Angle X-ray Scattering and X-ray Fluorescence experiments were also carried out to accurately interpret and complement the XPCI-CT findings as well as to obtain a detailed structural and chemical characterization of the detected pathological features. Overall, this multi-technique approach could detect: i) a different radio-sensitivity for the MRT-treated brain areas; ii) Ca and Fe deposits, hydroxyapatite crystals formation; iii) extended and isolated fibrotic contents. Full-organ XPCI-CT datasets allowed for the quantification of tumour and mi-crocalcifications’ volumes in treated brains and the amount of scarring tissue in irradiated lungs. Herein, the role of XPCI-CT as a 3D virtual histology technique for the follow-up of ex-vivo RT effects has been assessed as a complementary method for an accurate volumetric investigation of normal and pathological states in brains and lungs, in a small animal model. Moreover, the technique is proposed as a guidance and auxiliary tool for conventional histology, which is the gold standard for pathological evaluations, owing to its 3D capabilities and the possibility of virtually navigating within samples. This puts a landmark for XPCI-CT inclusion in the pre-clinical studies pipeline and for advancing towards in-vivo XPCI-CT imaging of treated organs.Weltweit gilt Krebs als häufigste bzw. zweithäufigste Ursache eines zu früh erfolgenden Todes, wobei die Zahlen rasch ansteigen. Standardmäßige Krebstherapien umfassen chirurgische Eingriffe, Chemotherapie und Strahlentherapie (radiotherapy, RT); oft kommt eine Kombination daraus zur Anwendung, um die Wahrscheinlichkeit der Tumorkontrolle zu erhöhen. Es wurden Standardtherapieprotokolle für zahlreiche Krebsarten eingerichtet und es wird vor allem in der Behandlung von strahlenresistenten Tumoren mit allgemein schlechter Prognose wie bei Hirn- und Lungentumoren an neuen Ansätzen geforscht. Nachverfolgungstechniken, welche die Auswirkungen von Therapien überwachen und ermitteln, sind zur Überwachung der Wirksamkeit herkömmlich angewandter Behandlungen wichtig und auch maßgeblich am Zugang zu den Fähigkeiten zur Heilung sowie zum Auftreten akuter und verzögerter Nebenwirkungen neuer Therapien beteiligt. In diesem Rahmenwerk unterbreitet diese Doktorarbeit die Technik der Röntgen-Phasenkontrast-Bildgebung über Computertomographie (X-ray Phase Contrast Imaging - Computed Tomography, XPCI‑CT) als bildverarbeitungs-basiertes Tool zur Untersuchung und Quantifizierung der Auswirkungen neuartiger Strahlentherapien, nämlich der Mikrobeam- und Minibeam-Strahlentherapie (MRT und MB), sowie zum Vergleich derselben mit den herkömmlichen durch Breitstrahlen (Broad Beam, BB) erzielten Auswirkungen auf Gehirn und Lunge. MRT und MB sind neuartige Strahlentherapien, die ein Array räumlich aufgeteilter Röntgenstrahlenbeamlets aus einer synchrotronen Strahlenquelle mit einer Breite von Zehnteln bzw. Hundersteln Mikrometern abgeben. MRT und MB nutzen den sogenannten Dosis-Volumen-Effekt: Hunderte Gray werden von gesundem Gewebe gut vertragen und wirken bei der Abgabe in einer Mikroebene im Mikrometerbereich vorrangig auf Tumorzellen und Blutgefäße, während sie bei einer Anwendung über größere gleichförmige Strahlungsfelder letale Auswirkungen aufweisen. Solche hoch kollimierten Röntgenstrahlen erfordern eine hohe Auflösung und einen Zugang zum gesamten Organ, bei dem die Auswirkungen der Behandlung entlang und außerhalb der Beamletpfade mit hoher Empfindlichkeit visualisiert werden können. Hier empfiehlt und bewährt sich die XPCI‑CT als leistungsstarke Bildverarbeitungstechnik, welche die Auswirkungen der Strahlung auf normale und tumortragende Gewebe feststellen und quantifizieren kann. Außerdem hat sich gezeigt, dass sie durch 3‑D-Informationen eine effektive Technik zur Ergänzung der histologischen Erkenntnisse in der Nachverfolgung der Strahlenbehandlung ist. Anhand eines mehrstufigen und multitechnischen röntgenbasierten Ansatzes habe ich die Auswirkungen der Strahlentherapie auf gesunde und von Glioblastomen (GBM) befallene Rattenhirne sowie auf gesunde Rattenlungen visualisiert und analysiert. Mit isotropen Voxelgrößen im Bereich von 3,53 bis 0,653 μm3 erfasste Ex-vivo-XPCI-CT-Datensätze konnten die idiopathischen Auswirkungen der MRT-, MB- und BB‑Behandlung mit hoher Empfindlichkeit unterscheiden. Es wurden auch Experimente zu Histologie, Immunhistochemie, Röntgenklein- und ‑weitwinkelstreuung und Röntgenfluoreszenz durchgeführt, um die XPCI‑CT-Erkenntnisse präzise zu interpretieren und zu ergänzen sowie eine detaillierte strukturelle und chemische Charakterisierung der nachgewiesenen pathologischen Merkmale zu erhalten. Im Allgemeinen wurde durch diesen multitechnischen Ansatz Folgendes ermittelt: i) eine un-terschiedliche Strahlenempfindlichkeit der mit MRT behandelten Gehirnbereiche; ii) Ca- und Fe-Ablagerungen und die Bildung von Hydroxylapatitkristallen; iii) ein ausgedehnter und isolierter Fibrosegehalt. XPCI‑CT-Datensätze des gesamten Organs ermöglichten die Quantifizierung der Volume von Tumoren und Mikroverkalkungen in den behandelten Gehirnen und der Menge des Narbengewebes in bestrahlten Lungen. Dabei wurde die Rolle der XPCI‑CT als virtuelle 3‑D-Histologietechnik für die Nachverfolgung von Ex-vivo-RT‑Auswirkungen als ergänzende Methode für eine präzise volumetrische Untersuchung des normalen und pathologischen Zustands von Gehirnen und Lungen im Kleintiermodell untersucht. Darüber hinaus wird die Technik aufgrund ihrer 3‑D-Fähigkeiten und der Möglichkeit zur virtuellen Navigation in den Proben als Leitfaden und Hilfstool für die herkömmliche Histologie vorgeschlagen, die der Goldstandard für die pathologische Evaluierung ist. Dies markiert einen Meilenstein für die Übernahme der XPCI‑CT in die Pipeline präklinischer Studien und für den Übergang zur In-vivo-XPCI‑CT von behandelten Organen

X-ray CT on the GPU

Nondestructive testing (NDT) is a collection of analysis techniques used by scientists and technologists as a way of analyzing the interior of an object without damaging the object. Since the analysis is done without damaging the object, NDT is an extremely valuable technique used in various industries for troubleshooting and research. CNDE has a long history of working with a variety of industrial sectors which include Aerospace (commercial and military aviation) and Defense Systems (ground vehicles and personnel protection); Energy (nuclear, wind, fossil); Infrastructure and Transportation (bridges, roadways, dams, levees); and Petro-Chemical (offshore, processing, fuel transport piping) to provide cost-effective tools and solutions. X-ray tomography is the procedure of using X-rays for generating tomographic slices of the required object. The object is bombarded with X-rays and the scanned image intensity values are collected on a detector. A significant drawback in X-ray tomography is the amount of data collected. It is generally huge in the order of gigabytes and hence the processing of data presents a big challenge. One way to speed up the processing of data is to run the programs on a cluster. CNDE uses a 64 node Beowulf cluster to do the reconstruction of an image. However with the advent of the GPU (Graphic Processing Unit) we have a far more cost efficient and time efficient hardware to run the reconstruction algorithm. The GPU can be fitted into a single PC, costs 10 times less than the cluster and also has a longer life time. This thesis has two major components to it. One of it is the desvelopment of new preprocessing and post processing techniques (includes filters, hot pixel removal etc.) to improve the quality of the input data and the other is the implementation of these techniques as well as the reconstruction program on the GPU using CUDA. Speedup on the GPU is not just a matter of porting the developed algorithms in parallel onto the hardware like in a cluster. GPU architecture is extremely complex and involves the usage of many different types of memory each with its own advantages and disadvantages and also many other optimization techniques for accessing and processing the data. These new techniques as well as the introduction of GPU are a significant addition to X-ray program here at CNDE

Tomografia estendida : do básico até o mapeamento de cérebro de camundongos

Orientador: Mateus Borba CardosoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: Esta tese apresentará uma introdução a imagens de raios-x e como adquirir e processar imagens usando linhas de luz síncrotron. Apresentará os desafios matemáticos e técnicos para reconstruir amostras em três dimensões usando a reconstrução de Tomografia Computadorizada, uma técnica conhecida como CT. Esta técnica tem seu campo de visão limitado ao tamanho da câmera e ao tamanho da iluminação. Uma técnica para ampliar esse campo de visão vai ser apresentada e os desafios técnicos envolvidos para que isso aconteça. Um \textit{pipeline} é proposto e todos os algoritmos necessários foram empacotados em um pacote python chamado Tomosaic. A abordagem baseia-se em adquirir tomogramas parciais em posiçoes pré definidas e depois mesclar os dados em um novo conjunto de dados. Duas maneiras possíveis são apresentadas para essa mescla, uma no domínio das projeções e uma no domínio dos sinogramas. Experimentos iniciais serão então usadas para mostrar que o método proposto funciona com computadores normais. A técnica será aplicada mais tarde para pesquisar a anatomia de cérebros de camundongo completos. Um estudo será apresentado de como obter informação em diferentes escalas do cérebro completo do rato utilizando raios-xAbstract: This thesis will present an introduction to x-ray images and how to acquire and thread images using synchrotron beamlines. It will present the mathematical and technical challenges to reconstruct samples in three dimensions using Computed Tomography reconstruction, a technique known as CT. This technique has a field of view bounded to the camera size and the illumination size. A technique to extended this field of view is going to be presented and the technical challenges involved in order for that to happen will be described. A pipeline is proposed and all the necessary algorithms are contained into a python packaged called Tomosaic. The approach relies on acquired partial tomogram data in a defined grid and later merging the data into a new dataset. Two possible ways are presented in order to that: in the projection domain, and in the sinogram domain. Initial experiments will then be used to show that the pipeline works with normal computers. The technique will be later applied to survey the whole anatomy of whole mouse brains. A study will be shown of how to get the complete range of scales of the mouse brain using x-ray tomography at different resolutionsDoutoradoFísicaDoutor em Ciências163304/2013-01247445/2013, 1456912/2014CNPQCAPE

Feature-preserving image restoration and its application in biological fluorescence microscopy

This thesis presents a new investigation of image restoration and its application to fluorescence cell microscopy. The first part of the work is to develop advanced image denoising algorithms to restore images from noisy observations by using a novel featurepreserving diffusion approach. I have applied these algorithms to different types of images, including biometric, biological and natural images, and demonstrated their superior performance for noise removal and feature preservation, compared to several state of the art methods. In the second part of my work, I explore a novel, simple and inexpensive super-resolution restoration method for quantitative microscopy in cell biology. In this method, a super-resolution image is restored, through an inverse process, by using multiple diffraction-limited (low) resolution observations, which are acquired from conventional microscopes whilst translating the sample parallel to the image plane, so referred to as translation microscopy (TRAM). A key to this new development is the integration of a robust feature detector, developed in the first part, to the inverse process to restore high resolution images well above the diffraction limit in the presence of strong noise. TRAM is a post-image acquisition computational method and can be implemented with any microscope. Experiments show a nearly 7-fold increase in lateral spatial resolution in noisy biological environments, delivering multi-colour image resolution of ~30 nm

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

Differential interferometry of QSO broad line regions I: improving the reverberation mapping model fits and black hole mass estimates

Reverberation mapping estimates the size and kinematics of broad line regions (BLR) in Quasars and type I AGNs. It yields size-luminosity relation, to make QSOs standard cosmological candles, and mass-luminosity relation to study the evolution of black holes and galaxies. The accuracy of these relations is limited by the unknown geometry of the BLR clouds distribution and velocities. We analyze the independent BLR structure constraints given by super-resolving differential interferometry. We developed a three-dimensional BLR model to compute all differential interferometry and reverberation mapping signals. We extrapolate realistic noises from our successful observations of the QSO 3C273 with AMBER on the VLTI. These signals and noises quantify the differential interferometry capacity to discriminate and measure BLR parameters including angular size, thickness, spatial distribution of clouds, local-to-global and radial-to-rotation velocity ratios, and finally central black hole mass and BLR distance. A Markov Chain Monte Carlo model-fit, of data simulated for various VLTI instruments, gives mass accuracies between 0.06 and 0.13 dex, to be compared to 0.44 dex for reverberation mapping mass-luminosity fits. We evaluate the number of QSOs accessible to measures with current (AMBER), upcoming (GRAVITY) and possible (OASIS with new generation fringe trackers) VLTI instruments. With available technology, the VLTI could resolve more than 60 BLRs, with a luminosity range larger than four decades, sufficient for a good calibration of RM mass-luminosity laws, from an analysis of the variation of BLR parameters with luminosity.Comment: 19 pages, 14 figures, accepted by MNRAS on December 5, 201

X-ray Phase-Contrast Tomography: Underlying Physics and Developments for Breast Imaging

X-ray phase-contrast tomography is a powerful tool to dramatically increase the visibility of features exhibiting a faint attenuation contrast within bulk samples, as is generally the case of light (low-Z) materials. For this reason, the application to clinical tasks aiming at imaging soft tissues, as e.g., breast imaging, has always been a driving force in the development of this field. In this context, the SYRMA-3D project, which constitutes the framework of the present work, aims to develop and implement the first breast computed tomography system relying on the propagation-based phase-contrast technique at the Elettra synchrotron facility (Trieste, Italy). This thesis finds itself in the \u2018last mile\u2019 towards the in-vivo implementation, and the obtained results add some of the missing pieces in the realization of the project. The first part of the work introduces a homogeneous mathematical framework describing propagation-based phase contrast from the sample-induced X-ray refraction, to detection, processing and tomographic reconstruction. The original results reported in the following chapters include the implementation of a pre-processing procedure dedicated for a novel photon-counting CdTe detector; a study, supported by a rigorous theoretical model, on signal and noise dependence on physical parameters such as propagation distance and detector pixel size; hardware and software developments for improving signal-to-noise ratio and reducing the scan time; and, finally, a clinically-oriented study based on comparisons with clinical mammographic and histological images. The last part of the thesis attempts to widen the experimental horizon: first, a quantitative image comparison of the synchrotron-based setup and a clinically available breast-CT scanner is presented and then a practical laboratory implementation is detailed, introducing a monochromatic propagation-based micro-tomography setup making use on a high-power rotating anode source

End-to-end Memory-Efficient Reconstruction for Cone Beam CT

Cone Beam CT plays an important role in many medical fields nowadays, but the potential of this imaging modality is hampered by lower image quality compared to the conventional CT. A lot of recent research has been directed towards reconstruction methods relying on deep learning. However, practical application of deep learning to CBCT reconstruction is complicated by several issues, such as exceedingly high memory costs of deep learning methods for fully 3D data. In this work, we address these limitations and propose LIRE: a learned invertible primal-dual iterative scheme for Cone Beam CT reconstruction. Memory requirements of the network are substantially reduced while preserving its expressive power, enabling us to train on data with isotropic 2mm voxel spacing, clinically-relevant projection count and detector panel resolution on current hardware with 24 GB VRAM. Two LIRE models for small and for large Field-of-View setting were trained and validated on a set of 260 + 22 thorax CT scans and tested using a set of 142 thorax CT scans plus an out-of-distribution dataset of 79 head \& neck CT scans. For both settings, our method surpasses the classical methods and the deep learning baselines on both test sets. On the thorax CT set, our method achieves PSNR of 33.84 $\pm$ 2.28 for the small FoV setting and 35.14 $\pm$ 2.69 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 $\pm$ 1.75 and 34.29 $\pm$ 2.71 respectively. On the head \& neck CT set, our method achieves PSNR of 39.35 $\pm$ 1.75 for the small FoV setting and 41.21 $\pm$ 1.41 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 $\pm$ 1.75 and 34.29 $\pm$ 2.71 respectively. Additionally, we demonstrate that LIRE can be finetuned to reconstruct high-resolution CBCT data with the same geometry but 1mm voxel spacing and higher detector panel resolution, where it outperforms the U-Net baseline as well