Feasibility assessment of the interactive use of a Monte Carlo algorithm in treatment planning for intraoperative electron radiation therapy

This work analysed the feasibility of using a fast, customized Monte Carlo (MC) method to perform accurate computation of dose distributions during pre- and intraplanning of intraoperative electron radiation therapy (IOERT) procedures. The MC method that was implemented, which has been integrated into a specific innovative simulation and planning tool, is able to simulate the fate of thousands of particles per second, and it was the aim of this work to determine the level of interactivity that could be achieved. The planning workflow enabled calibration of the imaging and treatment equipment, as well as manipulation of the surgical frame and insertion of the protection shields around the organs at risk and other beam modifiers. In this way, the multidisciplinary team involved in IOERT has all the tools necessary to perform complex MC dosage simulations adapted to their equipment in an efficient and transparent way. To assess the accuracy and reliability of this MC technique, dose distributions for a monoenergetic source were compared with those obtained using a general-purpose software package used widely in medical physics applications. Once accuracy of the underlying simulator was confirmed, a clinical accelerator was modelled and experimental measurements in water were conducted. A comparison was made with the output from the simulator to identify the conditions under which accurate dose estimations could be obtained in less than 3 min, which is the threshold imposed to allow for interactive use of the tool in treatment planning. Finally, a clinically relevant scenario, namely early-stage breast cancer treatment, was simulated with pre- and intraoperative volumes to verify that it was feasible to use the MC tool intraoperatively and to adjust dose delivery based on the simulation output, without compromising accuracy. The workflow provided a satisfactory model of the treatment head and the imaging system, enabling proper configuration of the treatment planning system and providing good accuracy in the dosage simulation.

Optimization of Monte Carlo code for clinical simulation of electron beams

The aim of this work is to optimize a Monte Carlo (MC) kernel for electron radiation therapy (IOERT) compatible with intraoperative usage and to integrate it within an existing IOERT dedicated treatment planning system (TPS)

Mejoras en el procesamiento de imágenes de TC para el tratamiento con radioterapia adaptativa del cáncer de próstata

El cáncer de próstata es el tipo de cáncer con mayor prevalencia entre los hombres del mundo occidental y, pese a tener una alta tasa de supervivencia relativa, es la segunda mayor causa de muerte por cáncer en este sector de la población. El tratamiento de elección frente al cáncer de próstata es, en la mayoría de los casos, la radioterapia externa. Las técnicas más modernas de radioterapia externa, como la radioterapia modulada en intensidad, permiten incrementar la dosis en el tumor mientras se reduce la dosis en el tejido sano. Sin embargo, la localización del volumen objetivo varía con el día de tratamiento, y se requieren movimientos muy pequeños de los órganos para sacar partes del volumen objetivo fuera de la región terapéutica, o para introducir tejidos sanos críticos dentro. Para evitar esto se han desarrollado técnicas más avanzadas, como la radioterapia guiada por imagen, que se define por un manejo más preciso de los movimientos internos mediante una adaptación de la planificación del tratamiento basada en la información anatómica obtenida de imágenes de tomografía computarizada (TC) previas a la sesión terapéutica. Además, la radioterapia adaptativa añade la información dosimétrica de las fracciones previas a la información anatómica. Uno de los fundamentos de la radioterapia adaptativa es el registro deformable de imágenes, de gran utilidad a la hora de modelar los desplazamientos y deformaciones de los órganos internos. Sin embargo, su utilización conlleva nuevos retos científico-tecnológicos en el procesamiento de imágenes, principalmente asociados a la variabilidad de los órganos, tanto en localización como en apariencia. El objetivo de esta tesis doctoral es mejorar los procesos clínicos de delineación automática de contornos y de cálculo de dosis acumulada para la planificación y monitorización de tratamientos con radioterapia adaptativa, a partir de nuevos métodos de procesamiento de imágenes de TC (1) en presencia de contrastes variables, y (2) cambios de apariencia del recto. Además, se pretende (3) proveer de herramientas para la evaluación de la calidad de los contornos obtenidos en el caso del gross tumor volumen (GTV). Las principales contribuciones de esta tesis doctoral son las siguientes: _ 1. La adaptación, implementación y evaluación de un algoritmo de registro basado en el flujo óptico de la fase de la imagen como herramienta para el cálculo de transformaciones no-rígidas en presencia de cambios de intensidad, y su aplicabilidad a tratamientos de radioterapia adaptativa en cáncer de próstata con uso de agentes de contraste radiológico. Los resultados demuestran que el algoritmo seleccionado presenta mejores resultados cualitativos en presencia de contraste radiológico en la vejiga, y no distorsiona la imagen forzando deformaciones poco realistas. 2. La definición, desarrollo y validación de un nuevo método de enmascaramiento de los contenidos del recto (MER), y la evaluación de su influencia en el procedimiento de radioterapia adaptativa en cáncer de próstata. Las segmentaciones obtenidas mediante el MER para la creación de máscaras homogéneas en las imágenes de sesión permiten mejorar sensiblemente los resultados de los algoritmos de registro en la región rectal. Así, el uso de la metodología propuesta incrementa el índice de volumen solapado entre los contornos manuales y automáticos del recto hasta un valor del 89%, cercano a los resultados obtenidos usando máscaras manuales para el registro de las dos imágenes. De esta manera se pueden corregir tanto el cálculo de los nuevos contornos como el cálculo de la dosis acumulada. 3. La definición de una metodología de evaluación de la calidad de los contornos del GTV, que permite la representación de la distribución espacial del error, adaptándola a volúmenes no-convexos como el formado por la próstata y las vesículas seminales. Dicha metodología de evaluación, basada en un nuevo algoritmo de reconstrucción tridimensional y una nueva métrica de cuantificación, presenta resultados precisos con una gran resolución espacial en un tiempo despreciable frente al tiempo de registro. Esta nueva metodología puede ser una herramienta útil para la comparación de distintos algoritmos de registro deformable orientados a la radioterapia adaptativa en cáncer de próstata. En conclusión, el trabajo realizado en esta tesis doctoral corrobora las hipótesis de investigación postuladas, y pretende servir como cimiento de futuros avances en el procesamiento de imagen médica en los tratamientos de radioterapia adaptativa en cáncer de próstata. Asimismo, se siguen abriendo nuevas líneas de aplicación futura de métodos de procesamiento de imágenes médicas con el fin de mejorar los procesos de radioterapia adaptativa en presencia de cambios de apariencia de los órganos, e incrementar la seguridad del paciente. I.2 Inglés Prostate cancer is the most prevalent cancer amongst men in the Western world and, despite having a relatively high survival rate, is the second leading cause of cancer death in this sector of the population. The treatment of choice against prostate cancer is, in most cases, external beam radiation therapy. The most modern techniques of external radiotherapy, as intensity modulated radiotherapy, allow increasing the dose to the tumor whilst reducing the dose to healthy tissue. However, the location of the target volume varies with the day of treatment, and very small movements of the organs are required to pull out parts of the target volume outside the therapeutic region, or to introduce critical healthy tissues inside. Advanced techniques, such as the image-guided radiotherapy (IGRT), have been developed to avoid this. IGRT is defined by more precise handling of internal movements by adapting treatment planning based on the anatomical information obtained from computed tomography (CT) images prior to the therapy session. Moreover, the adaptive radiotherapy adds dosimetric information of previous fractions to the anatomical information. One of the fundamentals of adaptive radiotherapy is deformable image registration, very useful when modeling the displacements and deformations of the internal organs. However, its use brings new scientific and technological challenges in image processing, mainly associated to the variability of the organs, both in location and appearance. The aim of this thesis is to improve clinical processes of automatic contour delineation and cumulative dose calculation for planning and monitoring of adaptive radiotherapy treatments, based on new methods of CT image processing (1) in the presence of varying contrasts, and (2) rectum appearance changes. It also aims (3) to provide tools for assessing the quality of contours obtained in the case of gross tumor volume (GTV). The main contributions of this PhD thesis are as follows: 1. The adaptation, implementation and evaluation of a registration algorithm based on the optical flow of the image phase as a tool for the calculation of non-rigid transformations in the presence of intensity changes, and its applicability to adaptive radiotherapy treatment in prostate cancer with use of radiological contrast agents. The results demonstrate that the selected algorithm shows better qualitative results in the presence of radiological contrast agents in the urinary bladder, and does not distort the image forcing unrealistic deformations. 2. The definition, development and validation of a new method for masking the contents of the rectum (MER, Spanish acronym), and assessing their impact on the process of adaptive radiotherapy in prostate cancer. The segmentations obtained by the MER for the creation of homogenous masks in the session CT images can improve significantly the results of registration algorithms in the rectal region. Thus, the use of the proposed methodology increases the volume overlap index between manual and automatic contours of the rectum to a value of 89%, close to the results obtained using manual masks for both images. In this way, both the calculation of new contours and the calculation of the accumulated dose can be corrected. 3. The definition of a methodology for assessing the quality of the contours of the GTV, which allows the representation of the spatial distribution of the error, adapting it to non-convex volumes such as that formed by the prostate and seminal vesicles. Said evaluation methodology, based on a new three-dimensional reconstruction algorithm and a new quantification metric, presents accurate results with high spatial resolution in a time negligible compared to the registration time. This new approach may be a useful tool to compare different deformable registration algorithms oriented to adaptive radiotherapy in prostate cancer In conclusion, this PhD thesis corroborates the postulated research hypotheses, and is intended to serve as a foundation for future advances in medical image processing in adaptive radiotherapy treatment in prostate cancer. In addition, it opens new future applications for medical image processing methods aimed at improving the adaptive radiotherapy processes in the presence of organ’s appearance changes, and increase the patient safety.

Incorporating equity into transport planning: utility, priority and sufficiency approaches

The analysis addresses the issue of transport equity and explores three different approaches to equity in transport: utilitarianism, sufficientarianism and prioritarianism. Each approach calls for a different treatment of the benefits reaped by different population groups in the assessment of transport investments or policies. In utilitarianism, which underlies much of the current practice of transport project appraisal, all benefits receive the same weight, irrespective of the recipient of the benefits. In both sufficientarianism and prioritarianism, benefits are weighed in distinct ways, depending on the characteristics of the recipients. The three approaches are illustrated using a fictive case study, in which three different transport investment are assessed and compared to each other. Finally, the assessment of transport investments will be explored using the cost-effectiveness analysis (CEA). The CEA assesses the distributional effects of transport investments for utilitarism, sufficientarism and prioritarism approaches and addresses distinct needs associated with different population groups in respect to their transport