Tesis por compendio / [ES] La tesi presentada a aquest document, s'emmarca dins de l'àmbit de la física mèdica. Dins d'aquesta branca de la física, es desenvolupen eines computacionals per oferir millores en la planificació de tractaments que involucren radiació ionitzant. En aquestes planificacions, es calculen factors dosimètrics com la dosi total absorbida tant, a la regió d'interès del tractaments, objectiu del mateix, com a la resta de teixits o òrgans de risc propers a la zona objectiu. Per poder efectuar aquests càlculs, existeixen diferents tècniques, sent les simulacions basades en Monte Carlo les considerades com l'eina més precisa. Aquest tipus de simulacions, permeten modelitzar els dispositius mèdics que emeten el feix de tractament als pacients, de forma detallada. A més, les simulacions Monte Carlo, permeten descriure les fonts de radiació minuciosament i considerar el transport de les partícules involucrades en el problema a través de la geometria considerada. En els treballs que conformen aquesta tesi, s'han emprat diferents codis Monte Carlo, depenent del problema a dur a terme. S'ha emprat MCNP6 a diferents treballs per la capacitat, i facilitat, de modelar geometries complexes emprant mallats volumètriques, penEasy com a codi per validar algunes de les eines dissenyades i penRed, per les característiques especialitzades en física mèdica, com la lectura i processament automàtic de DICOM i les fonts de braquiteràpia, el que faciliten molt les simulacions en l'entorn mèdic. Degut a estos fets, i a que penRed, és de codi obert i no requereix llicència, com al cas del MCNP, s'ha decidit estendre les capacitats que manquen en este, per poder equiparar el seu ús a la resta de codis en els problemes abordats durant la realització de la tesi doctoral. Tots aquests treballs contribueixen al desenvolupament d'eines que, mitjançant la simulació Monte Carlo, permeten optimitzar els càlculs en radioteràpia. Més encara, les eines desenvolupades, tenen una aplicabilitat més general i poden emprar-se en altres camps o problemes, com, per exemple, diagnòstic basat en imatge mèdica. El primer dels treballs, cobreix la necessita del codi MCNP6 de ser capaç de llegir i escriure fitxers d'espai de fase en format estàndard de la IAEA, eina que ja tenen implementadas molts dels codis de simulació Monte Carlo. Per suplir la manca de MCNP6 d'aquesta capacitat, es desenvolupa en aquesta tesi un codi capaç de realitzar aquestes conversions entre format d'espai de fase intern de MCNP6 i formats IAEA i a l'inrevés. Al segon treball, s'empren simulacions Monte Carlo per tal de dissenyar un filtre que homogeinitze el feix d'electrons de 12 MeV a l'eixida d'un accelerador de radioteràpia intraoperàtoria. El treball proporciona una configuració de filtre, dissenyada amb simulació Monte Carlo i validada amb altre grup d'investigació independent. El tercer treball, es basa en oferir una millora als elevats temps de computació a l'hora de realitzar planificacions de radioteràpia amb simulacions Monte Carlo per a tractaments amb diferents irradiacions angulars. Amb aquesta eina es pretén agilitzar significativament el procés de càlcul de distribució de dosi en el maniquí o pacient, sense haver de realitzar la simulació a través de tots els components de l'accelerador. Finalment, arrel d'haver emprat geometries basades en malles en les simulacions realitzades amb MCNP6, s'ha vist la importància d'aquesta capacitat, especialment en simulacions en l'àmbit de la física mèdica. La definició de geometries per descriure el sistema, és una part fonamental de qualsevol simulació, independentment del codi que s'utilitza per a dur-la a terme. És per això que, el quart treball, es centra en el desenvolupament d'un mòdul per a simular sobre geometries mallades en penRed. / [CA] La tesis presentada en este documento se enmarca dentro del ámbito de la física médica. Dentro de esta rama de la física, se desarrollan herramientas computacionales para ofrecer mejoras en la planificación de tratamientos que involucran radiación ionizante. En estas planificaciones, se calculan factores dosimétricos como la dosis total absorbida tanto en la región de interés del tratamiento, objetivo del mismo, como en el resto de tejidos u órganos de riesgo cercanos a la zona objetivo. Para poder llevar a cabo estos cálculos, existen diferentes técnicas, siendo las simulaciones basadas en Monte Carlo consideradas como la herramienta más precisa. Este tipo de simulaciones permiten modelar los dispositivos médicos que emiten el haz de tratamiento a los pacientes de forma detallada. Además, las simulaciones Monte Carlo permiten describir las fuentes de radiación minuciosamente y considerar el transporte de las partículas involucradas en el problema a través de la geometría considerada. En los trabajos que conforman esta tesis, se han empleado diferentes códigos Monte Carlo, dependiendo del problema a abordar. Se ha utilizado MCNP6 en diferentes trabajos por su capacidad y facilidad para modelar geometrías complejas utilizando mallas volumétricas, penEasy como código para validar algunas de las herramientas diseñadas y penRed, por sus características especializadas en física médica, como la lectura y procesamiento automático de DICOM y las fuentes de braquiterapia, lo que facilita mucho las simulaciones en el entorno médico. Debido a estos hechos, y a que penRed es de código abierto y no requiere licencia, como es el caso de MCNP, se ha decidido ampliar las capacidades que faltan en este, para poder equiparar su uso al resto de códigos en los problemas abordados durante la realización de la tesis doctoral. Todos estos trabajos contribuyen al desarrollo de herramientas que, mediante la simulación Monte Carlo, permiten optimizar los cálculos en radioterapia. Además, las herramientas desarrolladas tienen una aplicabilidad más general y pueden emplearse en otros campos o problemas, como por ejemplo, el diagnóstico basado en imagen médica. El primero de los trabajos cubre la necesidad del código MCNP6 de ser capaz de leer y escribir archivos de espacio de fase en formato estándar de la IAEA, herramienta que ya tienen implementadas muchos de los códigos de simulación Monte Carlo. Para suplir la falta de MCNP6 de esta capacidad, se desarrolla en esta tesis un código capaz de realizar estas conversiones entre formato de espacio de fase interno de MCNP6 y formatos IAEA y viceversa. En el segundo trabajo, se emplean simulaciones Monte Carlo para diseñar un filtro que homogenice el haz de electrones de 12 MeV en la salida de un acelerador de radioterapia intraoperatoria. El trabajo proporciona una configuración de filtro, diseñada con simulación Monte Carlo y validada con otro grupo de investigación independiente. El tercer trabajo se basa en ofrecer una mejora a los elevados tiempos de computación al realizar planificaciones de radioterapia con simulaciones Monte Carlo para tratamientos con diferentes irradiaciones angulares. Con esta herramienta se pretende agilizar significativamente el proceso de cálculo de distribución de dosis en el maniquí o paciente, sin tener que realizar la simulación a través de todos los componentes del acelerador. Finalmente, a raíz de haber empleado geometrías basadas en mallas en las simulaciones realizadas con MCNP6, se ha visto la importancia de esta capacidad, especialmente en simulaciones en el ámbito de la física médica. La definición de geometrías para describir el sistema es una parte fundamental de cualquier simulación, independientemente del código que se utilice para llevarla a cabo. Es por ello que el cuarto trabajo se centra en el desarrollo de un módulo para simular sobre geometrías malladas en penRed. / [EN] The thesis presented in this document falls within the scope of medical physics. Within this branch of physics, computational tools are developed to offer improvements in the planning of treatments involving ionizing radiation. In these plans, dosimetric factors are calculated, such as the total absorbed dose both in the region of interest of the treatment, which is the treatment's objective, and in the surrounding tissues or organs at risk near the target area. To perform these calculations, different techniques exist, with Monte Carlo simulations considered the most accurate tool. These simulations allow modeling of medical devices emitting the treatment beam to patients in detail. Furthermore, Monte Carlo simulations enable a detailed description of radiation sources and consider the transport of particles involved in the problem through the considered geometry. Different Monte Carlo codes have been used in the works comprising this thesis, depending on the problem addressed. MCNP6 has been used in various works for its capacity and ease in modeling complex geometries using volumetric meshes, penEasy as a code to validate some of the designed tools, and penRed for its specialized features in medical physics, such as reading and automatic processing of DICOM and brachytherapy sources, greatly facilitating simulations in the medical environment. Due to these facts, and because penRed is open-source and does not require a license, unlike MCNP, it has been decided to expand its capabilities to match its use with other codes in the problems addressed during the completion of the doctoral thesis. All of these works contribute to the development of tools that, through Monte Carlo simulation, optimize calculations in radiotherapy. Additionally, the developed tools have broader applicability and can be used in other fields or problems, such as diagnosis based on medical imaging. The first of the works covers the need for the MCNP6 code to be able to read and write phase space files in the standard IAEA format, a tool that many Monte Carlo simulation codes already have implemented. To address the lack of this capability in MCNP6, a code capable of performing these conversions between the internal phase space format of MCNP6 and IAEA formats, and vice versa, is developed in this thesis. In the second work, Monte Carlo simulations are used to design a filter that homogenizes the 12 MeV electron beam at the output of an intraoperative radiotherapy accelerator. The work provides a filter configuration, designed with Monte Carlo simulation and validated with another independent research group. The third work aims to improve the high computation times when performing radiotherapy planning with Monte Carlo simulations for treatments with different angular irradiations. This tool aims to significantly speed up the process of dose distribution calculation in the phantom or patient, without having to simulate through all components of the accelerator. Finally, due to having employed mesh-based geometries in simulations conducted with MCNP6, the importance of this capability has been recognized, especially in simulations in the field of medical physics. The definition of geometries to describe the system is a fundamental part of any simulation, regardless of the code used to perform it. Therefore, the fourth work focuses on the development of a module to simulate on meshed geometries in penRed. / This study was supported by the program “Ayudas para la promoción de empleo joven e implantación de la Garantía Juvenil en I+D+i, Plan Estatal de Investigación Científica y Técnica e Innovación 2017-2020” from the “Iniciativa de Empleo Juvenil” (IEJ) and the “Fondo Social Europeo” (FSE) We would like to acknowledge the Spanish “Ministerio de Ciencia e Innovación” (MCIN) grant PID2021-125096NB-I00 funded by MCIN/AEI/10.13039 and the “Generalitat Valenciana” (GVA) grant PROMETEO/2021/064. / Oliver Gil, S. (2024). Eines computacionals avançades per a planificació radioterapèutica mitjançat simulacions Monte Carlo [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/203890 / Compendio

Proton radiotherapy is a cancer treatment which has the potential to offer greater cure rates and/or fewer serious side effects than conventional radiotherapy. Its availability in the UK is currently limited to a single low-energy fixed beamline for the treatment of ocular tumours, but a number of facilities designed to treat deep-seated tumours are in development. This thesis focusses on the quantitative use of x-ray computed tomography (CT) images in planning proton radiotherapy treatments. It arrives at several recommendations that can be used to inform clinical protocols for the acquisition of planning scans, and their subsequent use in treatment planning systems. The primary tool developed is a software CT scanner, which simulates images of an anthropomorphic virtual phantom, informed by measurements taken on a clinical scanner. The software is used to investigate the accuracy of the stoichiometric method for calibrating CT image pixel values to proton stopping power, with particular attention paid to the impact of beam hardening and photon starvation artefacts. The strength of the method adopted is in allowing comparison between CT-estimated and exactly-calculated proton stopping powers derived from the same physical data (specified in the phantom), leading to results that are difficult to obtain otherwise. A number of variations of the stoichiometric method are examined, identifying the best-performing calibration phantom and CT tube voltage (kVp). Improvements in accuracy are observed when using a second-pass beam hardening correction algorithm. Also presented is a method for identifying the proton paths where stopping power uncertainties are likely to be greatest. Estimates of the proton range uncertainties caused by CT artefacts and calibration errors are obtained for a range of realistic clinical scenarios. The current practice of including planning margins equivalent to 3.5% of the range is found to ensure coverage in all but the very worst of cases. Results herein suggest margins could be reduced to <2% if the best-performing protocol is followed; however, an analysis specific to the CT scanner and treatment site in question should be carried out before such a change is made in the clinic.

Durant la dernière décennie, les développements technologiques en radiothérapie ont transformé considérablement les techniques de traitement. Les nouveaux faisceaux non standard améliorent la conformité de la dose aux volumes cibles, mais également complexifient les procédures dosimétriques. Puisque des études récentes ont démontré l’invalidité de ces protocoles actuels avec les faisceaux non standard, un nouveau protocole applicable à la dosimétrie de référence de ces faisceaux est en préparation par l’IAEA-AAPM. Le but premier de cette étude est de caractériser les facteurs responsables des corrections non unitaires en dosimétrie des faisceaux non standard, et ainsi fournir des solutions conceptuelles afin de minimiser l’ordre de grandeur des corrections proposées dans le nouveau formalisme de l’IAEA-AAPM. Le deuxième but de l’étude est de construire des méthodes servant à estimer les incertitudes d’une manière exacte en dosimétrie non standard, et d’évaluer les niveaux d’incertitudes réalistes pouvant être obtenus dans des situations cliniques. Les résultats de l’étude démontrent que de rapporter la dose au volume sensible de la chambre remplie d’eau réduit la correction d’environ la moitié sous de hauts gradients de dose. Une relation théorique entre le facteur de correction de champs non standard idéaux et le facteur de gradient du champ de référence est obtenue. En dosimétrie par film radiochromique, des niveaux d’incertitude de l’ordre de 0.3% sont obtenus par l’application d’une procédure stricte, ce qui démontre un intérêt potentiel pour les mesures de faisceaux non standard. Les résultats suggèrent également que les incertitudes expérimentales des faisceaux non standard doivent être considérées sérieusement, que ce soit durant les procédures quotidiennes de vérification ou durant les procédures de calibration. De plus, ces incertitudes pourraient être un facteur limitatif dans la nouvelle génération de protocoles. / During the past decade, technological developments in radiation therapy have considerably transformed treatment techniques. Novel nonstandard beams improve target dose conformity, but increase the complexity of dosimetry procedures. As recent studies demonstrated the invalidity of these protocols to nonstandard beams, a new protocol applicable to nonstandard beam reference dosimetry is in preparation by the IAEA-AAPM. The first goal of the study is to characterize the factors responsible for non-unity corrections in nonstandard beam dosimetry, and provide conceptual solutions to minimize the magnitude of the corrections. The second goal is to provide methods to estimate uncertainties accurately in nonstandard beam dosimetry, and estimate uncertainty levels achievable in typical clinical situations. Results of this study show that reporting dose to the sensitive volume of the chamber filled with water reduces the correction factor approximately by half under high gradients. A theoretical expression of correction factor is obtained for ideal nonstandard reference fields. In radiochromic film dosimetry, levels of uncertainty of the order of 0.3% are achieved with strict procedures and show great potential for nonstandard beam measurements. Results also suggest that experimental uncertainties in nonstandard beam are an important issue to consider both during daily QA routine and reference dosimetry, and could be a limiting factor in the new generation of protocols.

Monte Carlo (MC) and Pencil Beam (PB) calculations are compared to their measured planar dose distributions using a 2-D diode array for lung Stereotactic Body Radiation Therapy (SBRT). The planar dose distributions were studied for two different phantom types: an in-house heterogeneous phantom and a homogeneous phantom. The motivation is to mimic the human anatomy during a lung SBRT treatment and incorporate heterogeneities into the pre-treatment Quality Assurance process, where measured and calculated planar dose distributions are compared before the radiation treatment. Individual and combined field dosimetry has been performed for both fixed gantry angle (anterior to posterior) and planned gantry angle delivery. A gamma analysis has been performed for all beam arrangements. The measurements were obtained using the 2-D diode array MapCHECK 2™. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

A dosimetria de pacientes associada à avaliação das condições de funcionamento dos equipamentos médicos e aos procedimentos empregados na realização dos exames, desempenha um papel fundamental no sistema de proteção radiológica das exposições médicas. Nesse sentido, foi realizado um levantamento em grande escala das doses recebidas pelos pacientes submetidos a exames radiológicos convencionais realizados em uma amostra representativa de estabelecimentos de saúde do estado de São Paulo. Nesse levantamento foi empregado um kit dosimétrico postal originalmente desenvolvido, que permitiu a determinação da dose de entrada na pele (DEP) através da técnica de dosimetria termoluminescente. Paralelamente foram realizadas visitas in-loco a uma sub-amostra de estabelecimentos, onde as condições de funcionamento dos equipamentos de raios X médicos e do sistema de imagem foram avaliadas empregando-se procedimentos e equipamentos já estabelecidos em protocolos de controle de qualidade. O estudo completou-se com a elaboração de um catálogo de espectros na faixa de energia do radiodiagnóstico, que, através de procedimento desenvolvido, permitiu inferir espectros equivalentes em equipamentos médicos. Na determinação dos espectros foi empregado um detector semicondutor de telureto de cádmio e zinco (CdZnTe), cujas curvas de eficiência e escape foram determinadas experimentalmente para realização do processo de correção dos espectros (stripping procedure). O processo de amostragem de estabelecimentos de saúde realizado neste estudo permitiu verificar a distribuição de equipamentos de diagnóstico por imagem e a freqüência de exames radiológicos no estado de São Paulo. A partir desses resultados foram escolhidos os exames de tórax, crânio (e seios da face) e coluna para avaliação de DEP, uma vez que os mesmos apresentam as maiores freqüências anuais de exames por 1.000 habitantes: 100, 46 e 29, respectivamente. Na técnica de amostragem dos estabelecimentos de saúde incluídos neste estudo foi empregado como critério de estratificação a quantidade anual de exames radiológicos associados ao município de localização do estabelecimento. Do total de 200 estabelecimentos sorteados, 50 participaram da primeira etapa e 38 da segunda. Um total de 83 salas de exames (ou equipamentos) e 868 pacientes foram incluídos, e um conjunto de 1415 valores de DEP foi determinado. O resultado da distribuição dos valores de DEP permitiu determinar os chamados níveis de referência, que, no caso de pacientes adultos, se mostraram bastante semelhantes aos encontrados em outros estudos internacionais. No caso de pacientes infantis, a situação é bem diferente, obtendo-se valores pelo menos 2 vezes superiores a outros recomendados internacionalmente para a radiografia infantil mais freqüente (tórax). Esse fato sugere que as práticas empregadas na realização dos exames devem ser revisadas e que recomendações específicas a esse grupo de pacientes, a partir de estudos dirigidos, sejam publicadas. Constatou-se também alguns casos de DEP elevada pelo uso desnecessário de radioscopia de localização. Os testes de desempenho dos equipamentos e a avaliação das imagens realizadas sugerem que há possibilidade de melhoria das condições de realização dos exames, sem perda de informação diagnóstica presente na imagem e com redução das doses. Alguns espectros de raios X determinados experimentalmente apresentaram divergência em relação a outros catálogos já estabelecidos, numa faixa específica de energia do espectro (entre 25 e 40 keV). Para a sua utilização em situações práticas há necessidade de algumas correções na curva de eficiência, o que não inviabiliza a metodologia e os procedimentos estabelecidos. De forma geral, os resultados encontrados neste estudo permitem traçar um panorama das exposições médicas em radiologia convencional no estado de São Paulo, contribuindo para o aperfeiçoamento de futuras pesquisas que sejam realizadas na área, ou mesmo, para a implementação de políticas públicas. / Patients dosimetry, associated with the assessment of the performance of the radiological equipment and of the series of procedures employed in the accomplishment of the examinations, plays fundamental role in the radiation protection system of medical exposures. Therefore, a large-scale survey of absorbed doses was carried out in health services localized in the state of São Paulo, including patients submitted to conventional radiological examinations. In this survey a postal dosimetric kit, originally developed, was employed. It allows the evaluation of the entrance surface dose (ESD) to patients with thermoluminescence dosimeters. Also a series visits to a sub-sample of services was carried out, giving rise to the in-loco evaluation of the performance of the medical x-ray equipment and of the image system, using procedures and equipments already established in protocols of quality control. The study is completed with the elaboration of a catalogue of x-ray spectra, which provides means to infer the spectra generated by medical x-ray equipments. Measurements of x-ray spectra were carried out with a cadmium zinc telluride detector (CdZnTe), and the stripping procedure was performed taking into account both the contributions of efficiency and x-ray escape fraction, experimentally determined in this work. The stratified sampling technique furnished important data on the distribution of equipments and the annual frequency of examinations performed in the state of São Paulo. From these results radiological examinations of the chest, skull and sinus, and spine were selected for the evaluation of ESD, as their annual frequencies are the highest observed: 100, 46 and 29 per thousand inhabitants, respectively. The number of x-ray examinations carried out annually in the cities of the state was employed as the stratification criterion to construct the sample. From a total of 200 health services sampled, 50 agreed to participate of the first stage, and 38 of the second. A total of 83 rooms (or x-ray equipments) and 868 patients was included, and a set of 1415 values of ESD was measured. Diagnostic reference levels were determined with the outcomes of the distribution of ESD. For adult patients, the reference levels achieved are very similar to others obtained in international surveys. However, as far as pediatric patients are concerned, the situation is very different: the values found in this survey are twice larger than the international recommendations to chest radiography of children. This points out that the practices need to be revised and that specific recommendations to this patient group, following specific surveys, should be provided. Also, a series of high ESD values due to unnecessary localizing radioscopy were detected among our data. The results of the equipment performance tests and of the evaluation of image quality suggest that it is possible to improve the conditions of the examinations and to reduce doses to patients, without impairment of the diagnostic information. Some of the experimentally determined x-ray spectra show a discrepancy, when compared to other catalogue spectra, in a particular energy range 25 to 40 keV. The practical application of them will require some corrections in the efficiency curve, but the established methodology and procedures remain legitimate. In an extensive approach, the results of this study supply a panorama of medical exposures in conventional radiology in the state of São Paulo, contributing with resources to future research in the field and also to governmental actions.

Este trabalho teve como objetivo validar uma ferramenta computacional para a realização de simulações da interação de elétrons e da radiação X com a matéria, utilizando o método de Monte Carlo para possíveis estudos em radiologia diagnóstica. Para esse propósito, foi desenvolvido um programa computacional que simula a produção de radiação de um equipamento de raios X, com a finalidade de obter a distribuição de energia dos fótons que alcançam uma determinada região de interesse, sem a necessidade de medições experimentais. Outra tarefa realizada neste trabalho foi o cálculo da resposta de um detector do tipo CdTe, para possibilitar a correção de espectros medidos com esse detector em experimentos na faixa de energia de radiodiagnóstico. A ferramenta computacional escolhida para essas aplicações foi o Geant4, que é um conjunto de programas de distribuição livre relativamente novo e que é utilizado para simulações da interação da radiação com a matéria. Um dos principais diferenciais do Geant4 é o emprego da tecnologia de programação orientada a objetos e de técnicas avançadas de engenharia de software. Os resultados da etapa de simulação de espectros de energia produzidos por um equipamento de raios X mostram que o Geant4 pode ser utilizado para esta aplicação, mas com ressalvas na simulação de espectros de raios X com alvos com molibdênio para a região de mamografia, que é a situação onde as diferenças dos rendimentos de raios X característicos dos espectros simulados com os seus respectivos espectros de referência são maiores. Na etapa de simulação da detecção da radiação X por um detector do tipo CdTe são apresentados resultados com excelente acordo com os dados de referência. As diferenças encontradas devem ser mais influenciadas pelos efeitos de armadilhamento de cargas e do comportamento do campo elétrico no interior do cristal do detector, que são específicos para este detector e não fazem parte dos modelos físicos fornecidos pelo Geant4. Desta forma, a validação do Geant4 realizada neste trabalho mostrou algumas das possibilidades de uso desta versátil ferramenta na área de radiologia diagóstica. / The aim of this work was the validation of a computational tool applied in simulations of electrons and X ray interactions with matter, using the Monte Carlo method for possible studies in diagnostic radiology. To perform this task, a computational program was developed to simulate the radiation production of a X ray equipment, with the purpose of obtaining the photon energy distribution which comprehends the region of interest, without the necessity of experimental measurements. Another task carried through in this work was the calculation of a CdTe detector response, which was used in the correction of measured spectra with energy distribution typically found in diagnostic radiology. The employed computational tool was Geant4, which is a free distribution set of computational programs used for simulation of the passage of particles through matter. One of the main differentials of Geant4 is the exploitation of advanced software-engineering techniques and object-oriented technology. The results of the simulation of energy spectra produced by a X ray equipment show that Geant4 can be used for this application, but with restrictions concerning the simulation of X ray spectra from molybdenum targets in the mammography energy range. This is the situation where the differences of the characteristic X ray yield between the simulated and reference spectra are more pronounced. For the simulation of X ray measurements with a CdTe detector, the results showed excellent agreement with the reference data. In this case the discrepancies must be originated mainly by effects of charge trapping and the nonuniformity of the electric field inside the CdTe crystal. In resume, the validation of the Geant4 carried through in this work showed some of the possibilities for the use of this versatile tool in diagnostic radiology.

Thesis (Ph.D.)--Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology Program in Medical Engineering and Medical Physics, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Vita. / Includes bibliographical references. / by Jonathan Walker Valvano. / Ph.D.

Les atteintes cardiovasculaires consécutives à la radiothérapie font partie des effets secondaires tardifs soulevant de nombreuses interrogations au sein de la communauté scientifique, notamment du point de vue de la relation dose-Effet et des effets concomitants d’autres facteurs de risque (chimiothérapie, cholestérol, âge, tension artérielle,…). Les coronaropathies post-Radiques sont une des principales causes de morbidité cardiaque. Cependant, l’étude des doses reçues par les coronaires lors d’une radiothérapie requiert des approximations importantes, notamment d’un point de vue morphologique. Pour les études rétrospectives avec des dossiers médicaux anciens, les informations anatomiques sont réduites à des radiographies orthogonales et quelques contours au simulateur. Pour les dossiers médicaux plus récents, l’utilisation de l’imagerie scanner pour la planification de traitement permet la considération d’une anatomie 3D, toutefois extrêmement limitée pour les coronaires en raison d’une résolution et d’un contraste trop faibles. Par ailleurs, lors de la planification de traitement des patients traités actuellement, les doses reçues par les artères coronaires sont rarement quantifiées en clinique, et quand elles le sont, c’est au moyen d’une segmentation par a priori anatomique. Ce travail de thèse propose une utilisation originale des fantômes numériques hybrides afin d’étudier les doses aux coronaires dans le cadre de radiothérapies du sein gauche et du lymphome de Hodgkin.Au cours de la thèse, une méthode d’insertion de fantômes numériques hybrides au format DICOM dans le système de planification de traitement a été développée et validée. Elle a été adaptée et testée avec des informations anatomiques limitées aux radiographies comme c’est le cas pour les dossiers médicaux anciens, pour des traitements du sein gauche.La méthode a également été adaptée pour effectuer des reconstructions dosimétriques précises aux artères coronaires de patients traités par radiothérapie pour un lymphome de Hodgkin médiastinal, ayant bénéficié d’un suivi cardiovasculaire incluant le diagnostic de sténoses coronariennes à l’aide d’un coroscanner. Par une étude cas-Témoin, le risque de sténoses à un segment d’artère coronaire donné a été évalué comme étant multiplié par 1,049 à chaque Gray aditionnel sur la dose médiane au segment d’artère coronaire.Pour les dossiers actuels, les incertitudes associées à l’approche de segmentation par a priori anatomique des artères coronaires ont été estimées dans le cadre du traitement du sein gauche, en simulant différentes topologies réalistes d’artères coronaires dans un unique thorax et en évaluant les doses, pour une balistique donnée avec et sans irradiation de la chaîne mammaire interne. La variabilité inter-Topologique de la dose moyenne à l’artère coronaire la plus irradiée, l’interventriculaire antérieure, a été estimée à respectivement 35%et 19% avec et sans irradiation de la chaîne mammaire interne tandis qu’avec la dose aux 2% du volume de l’artère interventriculaire les plus irradiés, cette variabilité est respectivement de 76% et 49%.Enfin, l’ordre de grandeur des écarts entre des mesures par films radiochromiques et des calculs de dose du système de planification de traitement ISOgray en bordure de champ et hors du champ a été évalué pour des configurations simple (fantôme physique homogène parallélépipédique, champ carré ouvert) et complexe (fantôme physique anthropomorphe avec hétérogénéités, faisceaux tangentiels rectangulaires avec filtres en coin). Ces écarts sont jugés significatifs essentiellement en bordure de champ quelle que soit la configuration. / Cardiovascular diseases following radiotherapy are major secondary late effects raising questions among the scientific community, especially regarding the dose-Effect relationship and confounding risk factors (chemotherapy, cholesterolemia, age at treatment, blood pressure,…). Post-Radiation coronary diseases are one of the main causes of cardiac morbidity. Some approximations are made when coronary doses due to radiotherapy are estimated, especially regarding the morphology. For retrospective studies with old medical records, only radiographs are usually available with sometimes some contours made with a simulator. For recent medical records, CT scans displaying the anatomy in 3D are used for radiotherapy simulation but do not allow the coronary artery visualization due to low resolution and contrast. Currently, coronary doses are barely assessed in clinical practice, and when it is done, anatomical prior knowledge is generally used. This thesis proposes an original approach based on hybrid computational phantoms to study coronary artery doses following radiotherapy for left-Side breast cancer and Hodgkin lymphoma.During the thesis, a method inserting hybrid computational phantoms in a DICOM format into the treatment planning system has been developed and validated. It has been adapted and tested in conditions where only radiographs provide anatomical information, as with old medical records for left side breast radiotherapy.The method has also been adapted to perform precise dose reconstructions to the coronary artery for patients treated for a mediastinal Hodgkin lymphoma and diagnosed with coronary stenosis through a coroscanner. A case-Control study was carried out and the risk of coronary stenosis on a coronary artery segment was assessed to be multiplied by 1.049 at each additional gray on the median dose to the coronary artery segment.For recent medical records, coronary doses uncertainties related to an approach by anatomical prior knowledge segmentation were estimated for a left side breast radiotherapy by simulating different realistic coronary artery topologies in a single representative thorax anatomy and calculating doses due to beam sets, with and without irradiation of the internal mammary chain. The inter-Topology variability of the mean dose to the most irradiated coronary artery, the left descending coronary artery, was assessed to 35% and 19% with and without the internal mammary chain irradiation, respectively; and it was of 76% and 49%, respectively, considering the dose to the most irradiated 2% of this coronary artery volume.Finally, an order of magnitude of the differences between measurments by radiochromic films and dose calculations by the ISOgray treatment planning system in the peripheral field area, has been estimated by for both a simple configuration (parallelepiped physical phantom, homogeneous media, open square field) and a complex configuration (anthropomorphic physical phantom, heterogeneous media, rectangular tangential beams with wedge filter). These differences were judged significant essentially around the geometrical border of the irradiation field for both configuration.

O objetivo deste trabalho foi propor, caracterizar e avaliar, por meio de simulações computacionais, um sistema de detecção de um tomógrafo PET (Positron Emission Tomography) dedicado para pequenas regiões. Os principais fatores considerados para a modelagem do sistema foram: resolução energética, resolução espacial, sensibilidade de detecção e custo do sistema. O pacote GATE (Geant4 Application for Tomographic Emission), baseado no código de transporte de radiação Geant4, foi escolhido para as simulações. Como forma de acompanhar os avanços da tecnologia PET, o tomógrafo Q-PEM/DoPET, da Universidade de Pisa - Itália, foi simulado e um modelo óptico analítico foi proposto para comparação entre os resultados simulados e experimentais. Assim, a utilidade do modelo óptico foi demonstrada, pois o mesmo evita o tempo de computação excessivamente longo de uma simulação com os processos ópticos do GATE ativados. Foi feita a caracterização de um bloco detector que consiste de um cristal cintilador monolítico acoplado a uma matriz de fotodetectores, baseados na tecnologia das fotomultiplicadoras de silício. A posição da interação do fóton gama dentro do cristal foi determinada usando um método baseado na estimativa de parâmetros de um modelo que descreve a distribuição da intensidade dos sinais dos fótons ópticos coletados pela matriz de fotodetectores, de acordo com o local da interação. O método possui a capacidade de determinação da profundidade da interação dentro do cristal, o que diminui consideravelmente os erros de paralaxe. O bloco detector proposto também pode ter aplicação em outras áreas da física e afins que fazem uso da instrumentação nuclear e que necessitam de detectores sensíveis à posição. Foi proposto um sistema de detecção para um tomógrafo PET com aplicação na Mamografia por Emissão de Pósitrons - PEM (Positron Emission Mammography). O conceito proposto tem o potencial para aperfeiçoar a capacidade da tecnologia PET de visualizar, quantificar e caracterizar tumores de mama. O tomógrafo foi avaliado, onde os parâmetros de desempenho para uma fonte pontual de 22Na no centro do campo de visão e distância entre planos detectores de 10 cm foram: resolução energética em 511 keV de 12,1(3)%, resolução espacial 3D de 1;34(1) x 1;26(1) x 2;04(2)mm3 e sensibilidade de detecção de 8(1)%. Os resultados mostram que o conceito proposto possui desempenho compatível aos tomógrafos já existentes, além de ter um custo menor, por ser baseado em cristais cintiladores monolíticos. / The aim of this work was to propose, to characterize and to evaluate, by means of computational simulations, a detection system of a dedicated PET (Positron Emission Tomography) tomograph. The main factors considered for the system modeling were: energetic resolution, spatial resolution, detection sensitivity and system cost. The package GATE (Geant4 Application for Tomographic Emission), based on Geant4 radiation transport code, was chosen for the simulations. To follow the advances on PET technology, the Q-PEM/DoPET tomograph, from University of Pisa - Italy, was simulated and an analytical optical model was proposed for comparison between simulated and experimental results. Thus, the usefulness of the optical model was demonstrated, since it avoids the excessively long computation time when activating the optical processes in GATE. A block detector made of a monolithic scintillator crystal coupled to a photodetector array based on silicon photomultiplier technology was characterized. The interaction position of gamma radiation inside the crystal was determined using a method based on estimating parameters of a model which describes the signal distribution of the optical photons collected by the photodectetor array. The method has the ability of determining the depth of interaction inside the crystal, which decreases considerably parallax errors. The proposed block detector also can be used in other applications of nuclear instrumentation that require sensitive position detectors. A detection system of a PET tomograph was proposed to be applied in Positron Emission Mammography - PEM. The proposed design has the potential to improve the PET ability to visualize, quantify and characterize breast tumors. The tomograph performance was evaluated and the following parameters were obtained from an acquisition of a 22Na point source in the center of the field view and for a distance of 10 cm between the detector planes: energy resolution at 511 keV of 12,1(3)%, 3D spatial resolution of 1;34(1) x 1;26(1) x 2;04(2)mm3 and detection sensitivity of 8(1)%. The results show that the performance of the proposed design is similar to existing tomographs, in addition to have a lower cost due to the employment of monolithic crystals.

The general context of this work is the use of low energy photon sealed sources in brachytherapy. We have worked in particular on two isotopes: I-125 (mean energy of 27 keV) and Pd-103 (mean energy of 21 keV). The sealed sources are prepared as cylindrical seeds 4.5 mm in length and 0.8 mm in radius. Even if the external dimensions are standard, the internal design can be extremely different from one model to the other as the manufacturers try to improve the dosimetric characteristics of their sources. These isotopes are used mainly as permanent implants for prostate tumours but can also be used in the treatment of eye tumours. Compared to the higher energy photon sources, they offer the physical advantages of a safer manipulation from a radioprotection point of view and of the reduction of the dose to the surrounding healthy tissues. When performing a clinical treatment, it is absolutely mandatory to be able to report very precisely various parameters that can have an impact on the patient treatment outcomes. These parameters are, for example, the prescribed dose, the doses at different organs, the degree of uniformity that has been achieved on the target or some dose-volume information. The brachytherapy treatment planning systems (TPS) also permit more and more to conform the treatment to the patient anatomy, like in external treatments. In the case of prostate tumours, it has been possible for a few years, using ultrasound imaging, to check the positioning of the seeds and to calculate the dose distribution in real time during the implantation procedure. It is clear that to achieve a good precision in the treatment itself, the sources dosimetric characteristics must be known with a maximum of precision. As at these low energies the dosimetric characteristics are very dependant on the internal design, this implies a thorough study of any new source design. This is the subject of the first part of this work with the determination of the dosimetric characteristics of two new models of seed produced by the IBt Company. That determination has been done using measurements with thermoluminescent detectors and Monte Carlo calculations with two codes: MCNP4C and EGSnrc. The comparison of these two codes with the measurements has brought into evidence the necessity to use up to date cross section libraries during the calculations and to take into account the presence of the detectors during the measurements. However, the dosimetry is only one part of the problem when dealing with these low energy sources in radiotherapy. The irradiated materials are complex living tissues, composed of many substructures on which radiations have not always the same impact. It is now largely accepted that the most radiosensitive part of a living cell is the DNA. When photons interact with matter, they produce electrons that deposit their energy as ionisations and excitations of the atoms. These ionisations, if they occur with or close to the DNA molecule, are responsible for damaging it. That structure can support a certain amount of damage and stay functional thanks to repair mechanisms, but these mechanisms have limits in the way they can handle multiple breaks in the DNA strands. If these breaks are too close in space and time, repair is not possible and the cell dies. The density of ionisations increases when the energy of the incoming photon decreases so it is expected that low energy photons will have a higher efficiency at killing cells and so a higher Relative Biological Effect than high energy photons. To study that subject, one must reduce the volume of matter considered during energy deposition events to reach the sizes relevant for cells, micron or even nanometre volumes. That is why the part of radiation physics dealing with that problem is called microdosimetry. The second part of this work is dedicated to a theoretical microdosimetric study of these low energy photon sources using the microdosimetric functions for volumes of 1µm and a cluster analysis study for nanometric volumes. The two types of studies show that the photons of 20-30 keV are effectively more biologically efficient than high energy photons. The microdosimetric results give a ratio of the relative to Co-60 of 2.6 for Pd-103 and 2.2 for I-125, which is concordant with the experimental values published by Wuu et al. (1996). The cluster analysis also shows that the electrons generated by photons of 20-30 keV produce more high order clusters than electrons of 300 keV. The mean cluster order for clusters of 10 nm is 3.0 for Pd-103 and is 3.3 for I-125 compared to 2.1 for electrons of 300 keV. In this case, I-125 shows a higher mean cluster order, which is related to a potentially higher biological efficiency. This is explained by the fact that I-125 photons interact with a probability of 51% by Compton Effect, when that probability decreases to 27% for Pd-103. Compton interactions generate a high number of very low electrons that deposit their energy very locally with a very high density of ionisations. More radiobiological studies are needed to determine which volume site is more relevant and therefore which kind of study better reflects the reality. / Le cadre général de ce travail est l'utilisation de sources scellées de photons de basse énergie en curiethérapie. Nous avons travaillé en particulier avec deux isotopes : I-125 (énergie moyenne de 27 keV) et le Pd-103 (énergie moyenne de 21 keV). Les sources scellées se présentent sous la forme de grains cylindriques de 4.5 mm de long et 0.8 mm de rayon. Bien que les dimensions externes soient standards, la configuration interne peut être extrêmement différente d'un modèle à l'autre vu que les fabricants essaient d'améliorer les caractéristiques dosimétriques de leurs sources. Ces isotopes sont utilisés comme implants permanents pour les tumeurs de la prostate mais peuvent aussi être utilisés dans le traitement des tumeurs ophtalmiques. Comparés aux sources de plus haute énergie, ils offrent l'avantage physique d'une manipulation plus facile du point de vue de la radioprotection et d'une réduction de la dose aux tissus sains avoisinants. Lors d'un traitement clinique, il est important de pouvoir rapporter précisément certains paramètres qui peuvent avoir un impact sur les résultats du traitement pour le patient. Ces paramètres sont par exemple la dose prescrite, les doses à différents organes, le degré d'uniformité atteint sur le volume cible ou certaines information dose-volume. Les systèmes de calcul de dose pour la curiethérapie permettent également de mieux en mieux de conformer le traitement à l'anatomie du patient, comme en radiothérapie externe. Dans le cas des tumeurs de la prostate, il est possible depuis quelques années de vérifier la position des sources et de calculer les distributions de dose en temps réel lors de l'implantation grâce à l'utilisation d'une sonde ultrason. Il est clair que pour arriver à une bonne précision lors du traitement lui-même, il est indispensable de connaître les caractéristiques dosimétriques des sources avec un maximum de précision. Vu que, à ces basses énergies, les caractéristiques dosimétriques sont très dépendantes de la structure interne de sources, cela implique une étude minutieuse et complète de chaque nouveau modèle de grain mis sur le marché. Ceci forme le cadre de la première partie de ce travail qui est la détermination des caractéristiques dosimétriques de deux nouveaux modèles de grains produits par la compagnie IBt. Cette détermination a été réalisée grâce à l'utilisation de détecteurs thermoluminescents et de calculs de Monte Carlo avec deux codes : MCNP4C et EGSnrc. La comparaison de ces deux codes avec les mesures a permit de mettre en évidence la nécessité d'utiliser des bibliothèques de sections efficaces récentes lors des calculs et de prendre en compte la présence des détecteurs lors des mesures. Cependant, la dosimétrie est seulement une partie du problème de l'étude des sources de basse énergie utilisée en radiothérapie. Les milieux irradiés sont des tissus vivants complexes, composés de plusieurs sous-structures sur lesquelles les radiations n'ont pas toujours le même effet. Il est maintenant largement accepté que la partie la plus radiosensible d'une cellule vivante est la molécule d'ADN. Lorsque des photons interagissent avec la matière, ils produisent des électrons qui eux-mêmes déposent leur énergie sous forme d'ionisation et d'excitations des atomes. Ces ionisations, si elles se passent à proximité ou dans la molécule d'ADN, peuvent endommager celle-ci. Cette structure peut supporter une certaine quantité de dommages tout en restant fonctionnelle grâce à des mécanismes de réparation, mais ces mécanismes connaissent des limitations dans la manière dont ils peuvent gérer les cassures multiples des brins d'ADN. Si ces cassures sont trop proches dans le temps et l'espace, la réparation n'est plus possible et la cellule meurt. La densité d'ionisation augmente lorsque l'énergie du photon décroît. Il est donc attendu que les photons de basse énergie auront un efficacité accrue pour tuer les cellules et donc une plus haute Efficacité Biologique Relative que les photons de haute énergie. Pour étudier cet effet, il faut réduire le volume de matière considéré lors des évènements responsables du dépôt d'énergie afin d'atteindre des dimensions d'un ordre représentatif pour les cellules, microns ou même nanomètres. C'est pourquoi la partie de la physique des radiations dédiée à ce problème est appelée microdosimétrie. La seconde partie de ce travail est dédiée à une étude microdosimétrique théorique des ces sources de photons de basse énergie utilisant le concept de fonctions microdosimétriques pour des volumes de 1 µm et une analyse de cluster pour des volumes de l'ordre du nanomètre. Les deux types d'étude montrent que les photons de 20-30 keV sont effectivement plus efficaces radiobiologiquement que les photons de hautes énergie. Les résultats microdosimétriques donnent un rapport de yD relatif au Co-60 de 2.6 pour le Pd-103 et de 2.2 pour l'I-125, ce qui est concordant avec les valeurs expérimentales publiées par Wuu et al. (1996). L'analyse de cluster montre aussi que les électrons générés par les photons de 20-30 keV produisent plus de clusters d'ordre élevé que les électrons de 300 keV. L'ordre de cluster moyen pour des clusters de 10 nm est de 3.0 pour le 103Pd et de 3.3 pour l'I-125 comparé à 2.1 pour des électrons de 300keV. Dans ce cas, l'I-125 montre un ordre de cluster moyen plus élevé, ce qui est lié à une efficacité biologique potentiellement plus élevée. Ceci est expliqué par le fait que les photons de l'I-125 interagissent par effet Compton avec une probabilité de 51 %, cette probabilité tombe à 27 % dans le cas du Pd-103. Les interactions Compton génèrent un grand nombre d'électrons de très basse énergie qui déposent leur énergie très localement avec une très haute densité d'ionisations. D'autres études biologiques sont nécessaires pour déterminer quel volume est plus adapté et donc quel type d'étude reflète le mieux la réalité.