Optimization strategies for respiratory motion management in stereotactic body radiation therapy

Various challenges arise during the treatment of lung tumors with stereotactic body radiation therapy (SBRT), which is a form of hypofractionated high precision conformal radiation therapy delivered to small targets. The dose is applied in only a few fractions and respiratory organ and tumor motion is a source of uncertainty additional to interfractional set-up errors. Respiratory organ and tumor motion is highly patient-specific and it affects the whole radiotherapy treatment chain. In this thesis, motion management techniques for SBRT are evaluated and improved in a clinical setting. A clinical need for improvement has been present at the LMU university hospital for each issue addressed in this thesis: Initially, the usage of respiratory correlated computed tomography (4DCT), which is vital for SBRT treatment, was seen as impractical and prone to uncertainties in the data reconstruction in its current form. Therefore, the 4DCT reconstruction workflow has been improved to minimize these potential error sources. Secondly, treatment planning for tumors affected by respiratory motion was evaluated and subsequently improved. Finally, the treatment technique of respiratory gating was implemented at the clinic, which led to the need of evaluating the respiratory gating characteristics of the novel system configuration. At first, the 4DCT reconstruction workflow used in clinical practice was investigated, as in the presence of respiratory motion the knowledge of tumor position over time is essential in SBRT treatments. Using 4DCT, the full motion range of the individual tumor can be determined. However, certain 4DCT reconstruction methods can under- or overestimate tumor motion due to limitations in the data acquisition scheme and due to the incorrect sorting of certain X-ray computed tomography (CT) image slices into different respiratory phases. As the regular clinical workflow of cycle-based sorting (CBS) without maximum inspiration detection (and therefore no clear starting point for the individual breathing cycles) seemed to be affected by these potential errors, the usage of CBS with correct maximum detection and another sorting algorithm of the respiration states, so-called local amplitude-based sorting (LAS), both have been implemented for a reduction of image artifacts and improved 4DCT quality. The three phase binning algorithms have been investigated in a phantom study (using 10 different breathing waveforms) and in a patient study (with 10 different patients). The mis-representation of the tumor volume was reduced in both implemented sorting algorithms compared to the previously used CBS approach (without correct maximum detection) in the phantom and the patient study. The clinical recommendation was the use of CBS with improved maximum detection, as too many manual interventions would be needed for the LAS workflow. Secondly, a combination of the actual patient breathing trace during treatment, the log files generated by the linear accelerator (LINAC), and Monte Carlo (MC) four-dimensional (4D) dose calculations for each individual fraction was implemented as a 4D dose evaluation tool. This workflow was tested in a clinical environment for SBRT treatment planning on multiple CT datasets featuring: a native free-breathing 3DCT, an average intensity projection (AIP) as well as a maximum intensity projection (MIP), both obtained from the patient's 4DCT, and density overrides (DOs) in a 3DCT. This study has been carried out for 5 SBRT patients for three-dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) treatment plans. The dose has been recalculated on each 4DCT breathing phase according the the patient's breathing waveform and accumulated to the gross tumor volume (GTV) at the end-of-exhale (EOE) breathing phase using deformable image registration. Even though the least differences in planned and recalculated dose were found for AIP and MIP treatment planning, the results indicate a strong dependency on individual tumor motion due to the variability of breathing motion in general, and on tumor size. The combination of the patient's individual breathing trace during each SBRT fraction with 4D MC dose calculation based on the LINAC log file information leads to a good approximation of actual dose delivery. Finally, in order to ensure precise and accurate treatment for respiratory gating techniques, the technical characteristics of the LINAC in combination with a breathing motion monitoring system as s surrogate for tumor motion have to be identified. The dose delivery accuracy and the latency of a surface imaging system in connection with a modern medical LINAC were investigated using a dynamic breathing motion phantom. The dosimetric evaluation has been carried out using a static 2D-diode array. The measurement of the dose difference between gated and ungated radiation delivery was found to be below 1% (for clinical relevant gating levels of about 30%). The beam-on latency, or time delay, determined using radiographic films was found to be up to 851 ms±100 ms. With these known parameters, an adjustment of the pre-selected gating level or the internal target volume (ITV) margins could be made. With the highly patient-specific character of respiratory motion, lung SBRT faces many additional challenges besides the specific issues addressed in this thesis. However, the findings of this thesis have improved clinical workflows at the Department of Radiation Oncology of the LMU University hospital. In a future perspective, a workflow using evaluation of the actual 4D dose in combination with accurate 4DCT image acquisition and specialized treatment delivery (such as respiratory gating) has the potential for a safe further reduction of treatment margins and increased sparing of organs-at-risk (OARs) in SBRT without compromising tumor dose targeting accuracy

Optimization strategies for respiratory motion management in stereotactic body radiation therapy

Various challenges arise during the treatment of lung tumors with stereotactic body radiation therapy (SBRT), which is a form of hypofractionated high precision conformal radiation therapy delivered to small targets. The dose is applied in only a few fractions and respiratory organ and tumor motion is a source of uncertainty additional to interfractional set-up errors. Respiratory organ and tumor motion is highly patient-specific and it affects the whole radiotherapy treatment chain. In this thesis, motion management techniques for SBRT are evaluated and improved in a clinical setting. A clinical need for improvement has been present at the LMU university hospital for each issue addressed in this thesis: Initially, the usage of respiratory correlated computed tomography (4DCT), which is vital for SBRT treatment, was seen as impractical and prone to uncertainties in the data reconstruction in its current form. Therefore, the 4DCT reconstruction workflow has been improved to minimize these potential error sources. Secondly, treatment planning for tumors affected by respiratory motion was evaluated and subsequently improved. Finally, the treatment technique of respiratory gating was implemented at the clinic, which led to the need of evaluating the respiratory gating characteristics of the novel system configuration. At first, the 4DCT reconstruction workflow used in clinical practice was investigated, as in the presence of respiratory motion the knowledge of tumor position over time is essential in SBRT treatments. Using 4DCT, the full motion range of the individual tumor can be determined. However, certain 4DCT reconstruction methods can under- or overestimate tumor motion due to limitations in the data acquisition scheme and due to the incorrect sorting of certain X-ray computed tomography (CT) image slices into different respiratory phases. As the regular clinical workflow of cycle-based sorting (CBS) without maximum inspiration detection (and therefore no clear starting point for the individual breathing cycles) seemed to be affected by these potential errors, the usage of CBS with correct maximum detection and another sorting algorithm of the respiration states, so-called local amplitude-based sorting (LAS), both have been implemented for a reduction of image artifacts and improved 4DCT quality. The three phase binning algorithms have been investigated in a phantom study (using 10 different breathing waveforms) and in a patient study (with 10 different patients). The mis-representation of the tumor volume was reduced in both implemented sorting algorithms compared to the previously used CBS approach (without correct maximum detection) in the phantom and the patient study. The clinical recommendation was the use of CBS with improved maximum detection, as too many manual interventions would be needed for the LAS workflow. Secondly, a combination of the actual patient breathing trace during treatment, the log files generated by the linear accelerator (LINAC), and Monte Carlo (MC) four-dimensional (4D) dose calculations for each individual fraction was implemented as a 4D dose evaluation tool. This workflow was tested in a clinical environment for SBRT treatment planning on multiple CT datasets featuring: a native free-breathing 3DCT, an average intensity projection (AIP) as well as a maximum intensity projection (MIP), both obtained from the patient's 4DCT, and density overrides (DOs) in a 3DCT. This study has been carried out for 5 SBRT patients for three-dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) treatment plans. The dose has been recalculated on each 4DCT breathing phase according the the patient's breathing waveform and accumulated to the gross tumor volume (GTV) at the end-of-exhale (EOE) breathing phase using deformable image registration. Even though the least differences in planned and recalculated dose were found for AIP and MIP treatment planning, the results indicate a strong dependency on individual tumor motion due to the variability of breathing motion in general, and on tumor size. The combination of the patient's individual breathing trace during each SBRT fraction with 4D MC dose calculation based on the LINAC log file information leads to a good approximation of actual dose delivery. Finally, in order to ensure precise and accurate treatment for respiratory gating techniques, the technical characteristics of the LINAC in combination with a breathing motion monitoring system as s surrogate for tumor motion have to be identified. The dose delivery accuracy and the latency of a surface imaging system in connection with a modern medical LINAC were investigated using a dynamic breathing motion phantom. The dosimetric evaluation has been carried out using a static 2D-diode array. The measurement of the dose difference between gated and ungated radiation delivery was found to be below 1% (for clinical relevant gating levels of about 30%). The beam-on latency, or time delay, determined using radiographic films was found to be up to 851 ms±100 ms. With these known parameters, an adjustment of the pre-selected gating level or the internal target volume (ITV) margins could be made. With the highly patient-specific character of respiratory motion, lung SBRT faces many additional challenges besides the specific issues addressed in this thesis. However, the findings of this thesis have improved clinical workflows at the Department of Radiation Oncology of the LMU University hospital. In a future perspective, a workflow using evaluation of the actual 4D dose in combination with accurate 4DCT image acquisition and specialized treatment delivery (such as respiratory gating) has the potential for a safe further reduction of treatment margins and increased sparing of organs-at-risk (OARs) in SBRT without compromising tumor dose targeting accuracy

Developments in PET-MRI for Radiotherapy Planning Applications

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance (QA) procedures for such corrections are lacking. Therefore, a dynamic phantom that is PET and MR compatible is required. Additionally, respiratory motion characterization is needed for conformal radiotherapy of lung. 4D-CT can provide 3D motion characterization but suffers from poor soft-tissue contrast. In this thesis, I examine these problems, and present solutions in the form of improved MR-hardware AC techniques, a PET/MRI/CT-compatible tumour respiratory motion phantom for QA measurements, and a retrospective 4D-PET-MRI technique to characterise respiratory motion. Chapter 2 presents two techniques to improve upon current AC methods that use a standard helical CT scan for MRI hardware in PET-MRI. One technique uses a dual-energy computed tomography (DECT) scan to construct virtual monoenergetic image volumes and the other uses a tomotherapy linear accelerator to create CT images at megavoltage energies (1.0 MV) of the RF coil. The DECT-based technique reduced artefacts in the images translating to improved μ-maps. The MVCT-based technique provided further improvements in artefact reduction, resulting in artefact free μ-maps. This led to more AC of the breast coil. In chapter 3, I present a PET-MR-CT motion phantom for QA of motion-correction protocols. This phantom is used to evaluate a clinically available real-time dynamic MR images and a respiratory-triggered PET-MRI protocol. The results show the protocol to perform well under motion conditions. Additionally, the phantom provided a good model for performing QA of respiratory-triggered PET-MRI. Chapter 4 presents a 4D-PET/MRI technique, using MR sequences and PET acquisition methods currently available on hybrid PET/MRI systems. This technique is validated using the motion phantom presented in chapter 3 with three motion profiles. I conclude that our 4D-PET-MRI technique provides information to characterise tumour respiratory motion while using a clinically available pulse sequence and PET acquisition method

Task-Driven Trajectory Design for Endovascular Embolization

Computed Tomography (CT) is one of the most useful and widely applied imaging modalities, employed in both diagnostic and treatment planning purposes in the medical field. Circular and spiral acquisition trajectories are traditionally employed and work well in many cases. The advent of technologies such as robotic C-arms in interventional imaging allow for more complex data acquisitions, which enables potential improvements in image quality, increased field of view, and sampling. This capability has particular potential crucial in interventional cases where images may be compromised by complex anatomy or surgical tools. In this work, we present a paradigm that uses custom non-circular orbits and prior patient information along with segmentation and registration techniques to account for surgical tools and/or implants, to improve image quality. The framework leverages the anatomical model to optimize a parameterized source-detector trajectory for a variety of specific imaging tasks. We propose an overall workflow for orbit customization with investigations of the various workflow stages as well as the overall performance of the framework

Flow pattern analysis for magnetic resonance velocity imaging

Blood flow in the heart is highly complex. Although blood flow patterns have been investigated by both computational modelling and invasive/non-invasive imaging techniques, their evolution and intrinsic connection with cardiovascular disease has yet to be explored. Magnetic resonance (MR) velocity imaging provides a comprehensive distribution of multi-directional in vivo flow distribution so that detailed quantitative analysis of flow patterns is now possible. However, direct visualisation or quantification of vector fields is of little clinical use, especially for inter-subject or serial comparison of changes in flow patterns due to the progression of the disease or in response to therapeutic measures. In order to achieve a comprehensive and integrated description of flow in health and disease, it is necessary to characterise and model both normal and abnormal flows and their effects. To accommodate the diversity of flow patterns in relation to morphological and functional changes, we have described in this thesis an approach of detecting salient topological features prior to analytical assessment of dynamical indices of the flow patterns. To improve the accuracy of quantitative analysis of the evolution of topological flow features, it is essential to restore the original flow fields so that critical points associated with salient flow features can be more reliably detected. We propose a novel framework for the restoration, abstraction, extraction and tracking of flow features such that their dynamic indices can be accurately tracked and quantified. The restoration method is formulated as a constrained optimisation problem to remove the effects of noise and to improve the consistency of the MR velocity data. A computational scheme is derived from the First Order Lagrangian Method for solving the optimisation problem. After restoration, flow abstraction is applied to partition the entire flow field into clusters, each of which is represented by a local linear expansion of its velocity components. This process not only greatly reduces the amount of data required to encode the velocity distribution but also permits an analytical representation of the flow field from which critical points associated with salient flow features can be accurately extracted. After the critical points are extracted, phase portrait theory can be applied to separate them into attracting/repelling focuses, attracting/repelling nodes, planar vortex, or saddle. In this thesis, we have focused on vortical flow features formed in diastole. To track the movement of the vortices within a cardiac cycle, a tracking algorithm based on relaxation labelling is employed. The constraints and parameters used in the tracking algorithm are designed using the characteristics of the vortices. The proposed framework is validated with both simulated and in vivo data acquired from patients with sequential MR examination following myocardial infarction. The main contribution of the thesis is in the new vector field restoration and flow feature abstraction method proposed. They allow the accurate tracking and quantification of dynamic indices associated with salient features so that inter- and intra-subject comparisons can be more easily made. This provides further insight into the evolution of blood flow patterns and permits the establishment of links between blood flow patterns and localised genesis and progression of cardiovascular disease.Open acces

Development and Implementation of Fully 3D Statistical Image Reconstruction Algorithms for Helical CT and Half-Ring PET Insert System

X-ray computed tomography: CT) and positron emission tomography: PET) have become widely used imaging modalities for screening, diagnosis, and image-guided treatment planning. Along with the increased clinical use are increased demands for high image quality with reduced ionizing radiation dose to the patient. Despite their significantly high computational cost, statistical iterative reconstruction algorithms are known to reconstruct high-quality images from noisy tomographic datasets. The overall goal of this work is to design statistical reconstruction software for clinical x-ray CT scanners, and for a novel PET system that utilizes high-resolution detectors within the field of view of a whole-body PET scanner. The complex choices involved in the development and implementation of image reconstruction algorithms are fundamentally linked to the ways in which the data is acquired, and they require detailed knowledge of the various sources of signal degradation. Both of the imaging modalities investigated in this work have their own set of challenges. However, by utilizing an underlying statistical model for the measured data, we are able to use a common framework for this class of tomographic problems. We first present the details of a new fully 3D regularized statistical reconstruction algorithm for multislice helical CT. To reduce the computation time, the algorithm was carefully parallelized by identifying and taking advantage of the specific symmetry found in helical CT. Some basic image quality measures were evaluated using measured phantom and clinical datasets, and they indicate that our algorithm achieves comparable or superior performance over the fast analytical methods considered in this work. Next, we present our fully 3D reconstruction efforts for a high-resolution half-ring PET insert. We found that this unusual geometry requires extensive redevelopment of existing reconstruction methods in PET. We redesigned the major components of the data modeling process and incorporated them into our reconstruction algorithms. The algorithms were tested using simulated Monte Carlo data and phantom data acquired by a PET insert prototype system. Overall, we have developed new, computationally efficient methods to perform fully 3D statistical reconstructions on clinically-sized datasets

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