<p>Patients undergoing cardiac catheterization are potentially at risk of radiation-induced health effects from the interventional fluoroscopic X-ray imaging used throughout the clinical procedure. The amount of radiation exposure is highly dependent on the complexity of the procedure and the level of optimization in imaging parameters applied by the clinician. For cardiac catheterization, patient radiation dosimetry, for key organs as well as whole-body effective, is challenging due to the lack of fixed imaging protocols, unlike other common X-ray based imaging modalities. </p><p>Pediatric patients are at a greater risk compared to adults due to their greater cellular radio-sensitivities as well as longer remaining life-expectancy following the radiation exposure. In terms of radiation dosimetry, they are often more challenging due to greater variation in body size, which often triggers a wider range of imaging parameters in modern imaging systems with automatic dose rate modulation. </p><p>The overall objective of this dissertation was to develop a comprehensive method of radiation dose estimation for pediatric patients undergoing cardiac catheterization. In this dissertation, the research is divided into two main parts: the Physics Component and the Clinical Component. A proof-of-principle study focused on two patient age groups (Newborn and Five-year-old), one popular biplane imaging system, and the clinical practice of two pediatric cardiologists at one large academic medical center. </p><p>The Physics Component includes experiments relevant to the physical measurement of patient organ dose using high-sensitivity MOSFET dosimeters placed in anthropomorphic pediatric phantoms. </p><p>First, the three-dimensional angular dependence of MOSFET detectors in scatter medium under fluoroscopic irradiation was characterized. A custom-made spherical scatter phantom was used to measure response variations in three-dimensional angular orientations. The results were to be used as angular dependence correction factors for the MOSFET organ dose measurements in the following studies. Minor angular dependence (< ±20% at all angles tested, < ±10% at clinically relevant angles in cardiac catheterization) was observed.</p><p>Second, the cardiac dose for common fluoroscopic imaging techniques for pediatric patients in the two age groups was measured. Imaging technique settings with variations of individual key imaging parameters were tested to observe the quantitative effect of imaging optimization or lack thereof. Along with each measurement, the two standard system output indices, the Air Kerma (AK) and Dose-Area Product (DAP), were also recorded and compared to the measured cardiac and skin doses – the lack of correlation between the indices and the organ doses shed light to the substantial limitation of the indices in representing patient radiation dose, at least within the scope of this dissertation.</p><p>Third, the effective dose (ED) for Posterior-Anterior and Lateral fluoroscopic imaging techniques for pediatric patients in the two age groups was determined. In addition, the dosimetric effect of removing the anti-scatter grid was studied, for which a factor-of-two ED rate reduction was observed for the imaging techniques. </p><p>The Clinical Component involved analytical research to develop a validated retrospective cardiac dose reconstruction formulation and to propose the new Optimization Index which evaluates the level of optimization of the clinician’s imaging usage during a procedure; and small sample group of actual procedures were used to demonstrate applicability of these formulations.</p><p>In its entirety, the research represents a first-of-its-kind comprehensive approach in radiation dosimetry for pediatric cardiac catheterization; and separately, it is also modular enough that each individual section can serve as study templates for small-scale dosimetric studies of similar purposes. The data collected and algorithmic formulations developed can be of use in areas of personalized patient dosimetry, clinician training, image quality studies and radiation-associated health effect research.</p> / Dissertation

La protonthérapie est une technique avancée de radiothérapie qui permet de délivrer une dose élevée à la tumeur, tout en épargnant au mieux les tissus sains environnants, grâce aux propriétés balistiques des protons. Cependant, des particules secondaires, principalement des neutrons, sont créées par les interactions nucléaires que les protons initient dans les composantes de la ligne et de la salle de traitement, ainsi que dans le patient. Ces neutrons secondaires conduisent à des doses indésirables déposées aux tissus sains situés à distance du volume cible, dont la conséquence pourrait être une augmentation du risque de développement de seconds cancers chez les patients traités et en particulier chez les enfants. Cette thèse a pour objectif d’évaluer par calcul les doses dues aux neutrons secondaires reçues par des patients de différents âges traités à l’Institut Curie- centre de protonthérapie d’Orsay (ICPO) par des faisceaux de protons de 178 MeV pour des tumeurs intracrâniennes. Les traitements sont réalisés dans la nouvelle salle de l’ICPO équipée d’un bras isocentrique IBA. Les composants de la ligne et de la salle de traitement ainsi que la source de protons ont été modélisés à l’aide du code de calcul Monte Carlo MCNPX. Le modèle obtenu a été validé par une série de comparaisons de calculs à des mesures expérimentales. Ces comparaisons ont concerné : a) les distributions de doses latérales et en profondeur du faisceau de protons primaire dans un fantôme d’eau, b) la spectrométrie des neutrons en une point de la salle, c) les équivalents de doses ambiants en différents points de la salle et d) les doses à distance du volume cible au sein d’un fantôme physique anthropomorhe. Des accords satisfaisants ont été obtenus entre les calculs et les mesures, permettant ainsi de considérer le modèle comme validé.Les fantômes hybrides-voxels de différents âges, développés par l’Université de Floride ont été ensuite introduits dans le modèle et des calculs de doses dues aux neutrons secondaires aux différents organes de ces fantômes ont été réalisés. Les doses diminuent lorsque la distance de l’organe au champ de traitement augmente et lorsque l’âge du patient augmente. Un patient de 1 an peut recevoir des doses deux fois plus élevées qu’un adulte. La dose maximale, égale à 16,5 mGy pour un traitement délivrant 54 Gy à la tumeur, est reçue, pour le fantôme de 1 an, par les glandes salivaires. Une incidence latérale (gauche ou droite) du faisceau de protons peut délivrer des doses deux fois plus élevées qu’une incidence supérieure (gauche ou droite), et quatre fois plus élevées qu’une incidence antéro-supérieure pour certains organes. Des doses équivalentes aux organes dues aux neutrons ont été aussi calculées. Les facteurs de pondération wR des neutrons varient entre 4 et 10, et les doses équivalentes atteignent au maximum 155 mSv au cours d’un traitement complet. / Proton therapy is an advanced radiation therapy technique that allows delivering high doses to the tumor while saving the healthy surrounding tissues due to the protons’ ballistic properties. However, secondary particles, especially neutrons, are created during protons’ nuclear reactions in the beam-line and the treatment room components, as well as inside the patient. Those secondary neutrons lead to unwanted dose deposition to the healthy tissues located at distance from the target, which may increase the secondary cancer risks to the patients, especially the pediatric ones. The aim of this work was to calculate the neutron secondary doses received by patients of different ages treated at the Institut Curie-centre de Protonthérapie d’Orsay (ICPO) for intracranial tumors, using a 178 MeV proton beam. The treatments are undertaken at the new ICPO room equipped with an IBA gantry. The treatment room and the beam-line components, as well as the proton source were modeled using the Monte Carlo code MCNPX. The obtained model was then validated by a series of comparisons between model calculations and experimental measurements. The comparisons concerned: a) depth and lateral proton dose distributions in a water phantom, b) neutron spectrometry at one position in the treatment room, c) ambient dose equivalents at different positions in the treatment room and d) secondary absorbed doses inside a physical anthropomorphic phantom. A general good agreement was found between calculations and measurements, thus our model was considered as validated. The University of Florida hybrid voxelized phantoms of different ages were introduced into the MCNPX validated model, and secondary neutron doses were calculated to many of these phantoms’ organs. The calculated doses were found to decrease as the organ’s distance to the treatment field increases and as the patient’s age increases. The secondary doses received by a one year-old patient may be two times higher than the doses received by an adult. A maximum dose of 16.5 mGy for a whole treatment delivering 54 Gy to the tumor was calculated to the salivary glands of a one year-old phantom. The calculated doses for a lateral proton beam incidence (left or right) may be, for some organs, two times higher than doses for an upper incidence (left or right) and four times higher than doses for an antero-superior incidence. Neutron equivalent doses were also calculated for some organs. The neutron weighting factors wR were found to vary between 4 and 10 and the equivalent doses for the considered organs reached at maximum 155 mSv during a whole treatment.

Après l’incorporation de radionucléides dans l’organisme, l’imagerie quantitative en médecine nucléaire et l’anthroporadiométrie sont utilisés pour quantifier l’activité retenue. L’étalonnage de ces systèmes in vivo peut être amélioré afin de tenir en compte de la variabilité individuelle. En vue d’optimiser la mesure de l’activité retenue, des fantômes d’étalonnage innovants ont été réalisés par impression 3D. L’infographie 3D a été utilisée pour la conception, en parallèle avec un travail d’ingénierie permettant l’inclusion de radionucléides et l’adaptation aux besoins des utilisateurs. Un jeu de fantômes thyroïdiens adapté à l’âge a été développé et utilisé pour améliorer la mesure anthroporadiométrique thyroïdienne des enfants. À la suite d’une étude systématique, les coefficients d’étalonnage des installations de routine et de crise de l’IRSN ont été déterminés pour l’adulte et les enfants de 5, 10 et 15 ans. Un fantôme thyroïdien pathologique a été développé en plus du jeu de fantômes thyroïdiens dédié à la crise pour améliorer la mesure de fixation thyroïdienne en médecine nucléaire. Une étude multicentrique a été réalisée pour optimiser l’étalonnage afin de mieux personnaliser le traitement des pathologies bénignes de la thyroïde. Pour l’anthroporadiométrie pulmonaire, une famille de fantômes de poitrine a été développée pour améliorer la surveillance des travailleuses du nucléaire. Finalement, ce travail de recherche a permis de développer des fantômes adaptés aux besoins et de démontrer leur utilité pour la quantification de l’activité en dosimétrie interne. / Following the incorporation of radionuclides in the body, quantitative imaging in nuclear medicine and in vivo spectrometry measurements are used to quantify the retained activity. The calibration of these in vivo systems can be improved to take account of individual variability. To optimize the measurements of the activity retained, innovative calibration phantoms were created and manufactured by 3D printing. 3D computer graphics were used for the design, coupled with an engineering work allowing the inclusion of radionuclides and the fit to users’ needs. A set of age-specific thyroid phantoms has been developed and used to improve the thyroid in vivo measurement of children. Following a systematic study, the calibration coefficients for IRSN emergency and routine installations were determined for adults and 5, 10 and 15 year old children. A pathological thyroid phantom has been developed in addition to the set of thyroid phantoms dedicated to the emergency to improve the thyroid uptake measurement in nuclear medicine. A multicentre study was carried out to optimize the calibration so that treatment of thyroid benign diseases moves towards a better personalization. For lung in vivo measurement, a set of breast phantoms has been developed to improve the monitoring of female workers. Finally, this research work has allowed developing several phantoms adapted to the needs and their usefulness was proven for the quantification of the activity in internal dosimetry.

A presença da Medicina Nuclear como modalidade de obtenção de imagens médicas é um dos principais procedimentos utilizados hoje nos centros de saúde, tendo como grande vantagem a capacidade de analisar o comportamento metabólico do paciente, traduzindo-se em diagnósticos precoces. Entretanto, sabe-se que a quantificação em Medicina Nuclear é dificultada por diversos fatores, entre os quais estão a correção de atenuação, espalhamento, algoritmos de reconstrução e modelos assumidos. Neste contexto, o principal objetivo deste projeto foi melhorar a acurácia e a precisão na análise de imagens de PET/CT via processos realísticos e bem controlados. Para esse fim, foi proposta a elaboração de uma estrutura modular, a qual está composta por um conjunto de passos consecutivamente interligados começando com a simulação de phantoms antropomórficos 3D para posteriormente gerar as projeções realísticas PET/CT usando a plataforma GATE (com simulação de Monte Carlo), em seguida é aplicada uma etapa de reconstrução de imagens 3D, na sequência as imagens são filtradas (por meio do filtro de Anscombe/Wiener para a redução de ruído Poisson caraterístico deste tipo de imagens) e, segmentadas (baseados na teoria Fuzzy Connectedness). Uma vez definida a região de interesse (ROI) foram produzidas as Curvas de Atividade de Entrada e Resultante requeridas no processo de análise da dinâmica de compartimentos com o qual foi obtida a quantificação do metabolismo do órgão ou estrutura de estudo. Finalmente, de uma maneira semelhante imagens PET/CT reais fornecidas pelo Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) foram analisadas. Portanto, concluiu-se que a etapa de filtragem tridimensional usando o filtro Anscombe/Wiener foi relevante e de alto impacto no processo de quantificação metabólica e em outras etapas importantes do projeto em geral. / The presence of Nuclear Medicine as a medical imaging modality is one of the main procedures utilized nowadays in medical centers, and the great advantage of that procedure is its capacity to analyze the metabolic behavior of the patient, resulting in early diagnoses. However, the quantification in Nuclear Medicine is known to be complicated by many factors, such as degradations due to attenuation, scattering, reconstruction algorithms and assumed models. In this context, the goal of this project is to improve the accuracy and the precision of quantification in PET/CT images by means of realistic and well-controlled processes. For this purpose, we proposed to develop a framework, which consists in a set of consecutively interlinked steps that is initiated with the simulation of 3D anthropomorphic phantoms. These phantoms were used to generate realistic PET/CT projections by applying the GATE platform (with Monte Carlo simulation). Then a 3D image reconstruction was executed, followed by a filtering process (using the Anscombe/Wiener filter to reduce Poisson noise characteristic of this type of images) and, a segmentation process (based on the Fuzzy Connectedness theory). After defining the region of interest (ROI), input activity and output response curves are required for the compartment analysis in order to obtain the Metabolic Quantification of the selected organ or structure. Finally, in the same manner real images provided from the Heart Institute (InCor) of Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HC-FMUSP) were analysed. Therefore, it is concluded that the three-dimensional filtering step using the Ascombe/Wiener filter was preponderant and had a high impact on the metabolic quantification process and on other important stages of the whole project.

A presença da Medicina Nuclear como modalidade de obtenção de imagens médicas é um dos principais procedimentos utilizados hoje nos centros de saúde, tendo como grande vantagem a capacidade de analisar o comportamento metabólico do paciente, traduzindo-se em diagnósticos precoces. Entretanto, sabe-se que a quantificação em Medicina Nuclear é dificultada por diversos fatores, entre os quais estão a correção de atenuação, espalhamento, algoritmos de reconstrução e modelos assumidos. Neste contexto, o principal objetivo deste projeto foi melhorar a acurácia e a precisão na análise de imagens de PET/CT via processos realísticos e bem controlados. Para esse fim, foi proposta a elaboração de uma estrutura modular, a qual está composta por um conjunto de passos consecutivamente interligados começando com a simulação de phantoms antropomórficos 3D para posteriormente gerar as projeções realísticas PET/CT usando a plataforma GATE (com simulação de Monte Carlo), em seguida é aplicada uma etapa de reconstrução de imagens 3D, na sequência as imagens são filtradas (por meio do filtro de Anscombe/Wiener para a redução de ruído Poisson caraterístico deste tipo de imagens) e, segmentadas (baseados na teoria Fuzzy Connectedness). Uma vez definida a região de interesse (ROI) foram produzidas as Curvas de Atividade de Entrada e Resultante requeridas no processo de análise da dinâmica de compartimentos com o qual foi obtida a quantificação do metabolismo do órgão ou estrutura de estudo. Finalmente, de uma maneira semelhante imagens PET/CT reais fornecidas pelo Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) foram analisadas. Portanto, concluiu-se que a etapa de filtragem tridimensional usando o filtro Anscombe/Wiener foi relevante e de alto impacto no processo de quantificação metabólica e em outras etapas importantes do projeto em geral. / The presence of Nuclear Medicine as a medical imaging modality is one of the main procedures utilized nowadays in medical centers, and the great advantage of that procedure is its capacity to analyze the metabolic behavior of the patient, resulting in early diagnoses. However, the quantification in Nuclear Medicine is known to be complicated by many factors, such as degradations due to attenuation, scattering, reconstruction algorithms and assumed models. In this context, the goal of this project is to improve the accuracy and the precision of quantification in PET/CT images by means of realistic and well-controlled processes. For this purpose, we proposed to develop a framework, which consists in a set of consecutively interlinked steps that is initiated with the simulation of 3D anthropomorphic phantoms. These phantoms were used to generate realistic PET/CT projections by applying the GATE platform (with Monte Carlo simulation). Then a 3D image reconstruction was executed, followed by a filtering process (using the Anscombe/Wiener filter to reduce Poisson noise characteristic of this type of images) and, a segmentation process (based on the Fuzzy Connectedness theory). After defining the region of interest (ROI), input activity and output response curves are required for the compartment analysis in order to obtain the Metabolic Quantification of the selected organ or structure. Finally, in the same manner real images provided from the Heart Institute (InCor) of Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HC-FMUSP) were analysed. Therefore, it is concluded that the three-dimensional filtering step using the Ascombe/Wiener filter was preponderant and had a high impact on the metabolic quantification process and on other important stages of the whole project.