No Brasil, para fins de planejamento de barreiras físicas em instalações radiográficas ou para a verificação dos níveis de restrição de dose em levantamentos radiométricos, deve ser usada a grandeza operacional equivalente de dose ambiente. Na prática, os monitores de radiação utilizados em proteção radiológica apresentam suas leituras na grandeza dosimétrica kerma no ar. Portanto, é preciso utilizar um coeficiente que converta esta grandeza dosimétrica na grandeza operacional recomendada. As normas nacionais estabelecem que o coeficiente de conversão no valor de 1,14 Sv/Gy deve ser usado para realizar esta operação, desconsiderando a diferença na distribuição espectral dos fótons dos feixes de raios X comumente encontrados em salas de radiologia convencional. O presente trabalho tem por objetivo determinar os coeficientes de conversão considerando a distribuição espectral da radiação secundária e secundária transmitida através de placas de argamassa baritada. Para atingir os objetivos propostos, foi desenvolvida uma metodologia experimental para as medições dos espectros das radiações secundárias e secundárias transmitidas usando um sistema espectroscópico com detector de CdTe e uma câmara de ionização de 1800 cm3. A região torácica de um objeto simulador antropomórfico, RANDO® Man, foi usada como região espalhadora. Foram utilizadas tensões no tubo entre 40 kV e 150 kV com intervalos na tensão de 10 kV. Os ângulos de espalhamento foram de 30°, 60°, 90° 120° e 150° em relação ao eixo do feixe primário. Como atenuador da radiação secundária foram utilizadas placas de argamassa baritada com espessuras de aproximadamente 10, 15, 20 e 25 mm. Os resultados mostram que, para a radiação secundária, os coeficientes de conversão são maiores que o valor estabelecido no Brasil. Num exemplo típico de levantamento radiométrico, a estimativa do equivalente de dose ambiente determinado usando o coeficiente de conversão calculado a partir dos espectros resultou em um valor cerca de 40 % superior ao equivalente de dose ambiente calculado a partir do coeficiente adotado pela norma nacional. / In Brazil, for planning purposes of the physical barriers in a radiographic installation and for levels verification of dose restriction in radiometric surveys, the ambient dose equivalent operational quantity should be used. In practice, radiation monitors used in radiation protection, are calibrated in dosimetry quantity air kerma. Therefore, it is important to use a conversion coefficient, which turns this dosimetric quantity into a recommended operational quantity. The rules followed in Brazil still establish that the value of the conversion coefficient, 1.14 Sv/Gy, must be used in area monitoring, disregarding differences between the beam types with different photon spectral distribution, commonly found in conventional radiology rooms. Consequently, this work aims to determine the conversion coefficients considering the spectral distribution of the secondary radiation and secondary-transmitted radiation through barium mortar plates. To achieve the proposed objectives, it has been developed an experimental method for measurement of secondary and secondary transmitted spectra using a spectroscopic system with CdTe detector and an ionization chamber 1800 cm3. The thoracic region of an anthropomorphic phantom, RANDO® Man, was used as a scatter region. The voltages used began 40 kV up to 150 kV in displacements of 10 kV, the scattering angles were 30°, 60°, 90° 120° and 150° with respect to the axis of the primary beam. As attenuator object of the secondary radiation was used barium mortar plates with thicknesses of 10, 15, 20 and 25 mm approximately. The results show that for the secondary radiation, the conversion coefficients are greater than the value set in Brazil. In a typical example of radiometric survey, the estimated ambient dose equivalent using the conversion coefficient calculated from the spectra, is a 40% higher compared to the value obtained using the coefficient recommended in Brazil.

L'imagerie par résonance magnétique (IRM) est une technique médicale incontournable permettant d'observer l'intérieur du corps de façon non invasive et non irradiante. L'IRM reste cependant connue pour souffrir d'une très faible sensibilité. Pour pallier cette limitation, une solution de choix est d'utiliser des espèces hyperpolarisées. Parmi les entités dont on peut augmenter la polarisation nucléaire et donc le signal RMN de plusieurs ordres de grandeur, le xénon se distingue par sa capacité à interagir avec son environnement proche, ce qui se traduit par une large gamme de déplacement chimique. L'objectif devient alors d'utiliser le xénon hyperpolarisé comme traceur. Le sujet de cette thèse porte sur le concept de sonde IRM 129Xe hyperpolarisé par laser pour la détection d'évènements biologiques. Dans cette approche, le xénon est vectorisé vers des cibles au moyen de systèmes hôtes fonctionnalisés puis détecté grâce à des séquences d'imagerie rapide. La conception et la mise au point d'un montage permettant la production de xénon hyperpolarisé par pompage optique par échange de spin sont décrites. Sont ensuite développées des études sur l'interaction du gaz rare avec de nouveaux cryptophanes susceptibles de constituer des molécules hôtes performantes. La mise en place de séquences IRM adaptées au caractère transitoire de l'hyperpolarisation et permettant l'utilisation optimale de l'échange du xénon dans les différents environnements est présentée. Des applications de biosondes IRM 129Xe pour la détection de cations métalliques et de récepteurs de surface cellulaire sont également décrites. Enfin, nos premiers résultats sur un modèle petit animal sont abordés.

A unique tool is developed that allows the user to model physical representations of complicated glovebox facilities in two dimensions and determine neutral-particle flux and ambient dose-equivalent fields throughout that geometry. The code Pandemonium, originally designed to determine flux and dose rates only, has been improved to include realistic glovebox geometries, time-dependent source and detector positions, time-dependent shielding thickness calculations, time-integrated doses, a representative criticality accident scenario based on time-dependent reactor kinetics, and more rigorous photon treatment. The photon model has been significantly enhanced by expanding the energy range to 10 MeV to include fission photons, and by including a set of new buildup factors, the result of an extensive study into the previously unknown "purely-angular effect" on photon buildup. Purely-angular photon buildup factors are determined using discrete ordinates and coupled electron-photon cross sections to account for coherent and incoherent scattering and secondary photon effects of bremsstrahlung and florescence. Improvements to Pandemonium result in significant modeling capabilities for processing facilities using intense neutron and photon sources, and the code obtains comparable results to Monte Carlo calculations but within a fraction of the time required to run such codes as MCNPX.

The Coarse-Mesh Transport Method (COMET) is a method developed by the Computational Reactor and Medical Physics Group at Georgia Tech. Its original application was neutron transport for nuclear reactor modeling. COMET has since been shown to be effective for coupled photon-electron transport calculations where the goal is to determine the energy deposition of a photon beam. So far COMET can simulate a mono-directional, mono-energetic, spatially-flat photon beam. The goal of this thesis will be to extend COMET by adding a generalized source treatment. The new source will be able to simulate beams that vary in intensity as a function of position, angle, and energy. EGSnrc will be used to verify the accuracy of the new method for 3D photon kerma calculations.

La planification de traitement en radiothérapie nécessite un calcul précis de la dose délivrée au patient. La méthode la plus fiable pour y parvenir est la simulation du transport des particules par technique Monte Carlo. Cette thèse constitue la première étude concernant la validation de la plateforme de simulation Monte Carlo GATE (GEANT4 Application for Tomographic Emission), basée sur les librairies de GEANT4 (GEometry ANd Tracking), pour le calcul de la dose absorbée déposée par des faisceaux d'électrons. L'objectif de cette thèse est de montrer que GATE/GEANT4 est capable d'atteindre le niveau d'exigences requis pour le calcul de la dose absorbée lors d'une planification de traitement, dans des situations où les algorithmes analytiques, actuellement utilisés dans les services de radiothérapie, n'atteignent pas un niveau de précision satisfaisant. L'enjeu est de prouver que GATE/GEANT4 est adapté pour la planification de traitement utilisant des électrons et capable de rivaliser avec d'autres codes Monte Carlo reconnus. Cet enjeu a été démontré par la simulation avec GATE/GEANT4 de faisceaux et des sources d'électrons réalistes utilisées en radiothérapie externe ou en radiothérapie moléculaire et la production de distributions de dose absorbée en accord avec les mesures expérimentales et avec d'autres codes Monte Carlo de référence pour la physique médicale. Par ailleurs, des recommandations quant à l'utilisation des paramètres de simulation à fixer, assurant un calcul de la distribution de dose absorbée satisfaisant les spécifications en radiothérapie, sont proposées.

The use of beamlets as a dose calculation tool in Intensity Modulated Radiation Therapy (IMRT) treatment planning is widespread and well documented. A beamlet can simply be defined as the contribution of radiation passing through a particular geometrically defined subdivision of a given linear accelerator's emerging radiation field. The most common classes of algorithms used today to calculate the dose distributions deposited by beamlets are the pencil beam convolution and col-lapsed cone classes of algorithms. Using BEAMnrc [1], a Monte Carlo (MC) based radiation transport simulation software package, this thesis presents a novel method of calculating MC beamlet dose distributions with a level of accuracy not achievable using the above analytic dose calculation methods. In a first application, the MC beamlet dose distributions generated in this thesis are used to fine-tune the output of the MC or "virtual" linear accelerator from which they are produced. This is achieved through the adjustment of individual beamlet weights to align the output of the virtual accelerator to the experimentally measured output of the modeled accelerator in water. In a second application, MC beamlets are used to derive corrections to particular Multileaf Collimator (MLC) leaf sequences of IMRT treatment plans that have been miscalculated by a convolution-based dose calculation algorithm. These calculation inaccuracies (up to as much as 15%) arise due to the well known fact that convolution-based algorithms do not accurately model dose deposition in inhomoge¬neous media, such as lung [2] [3] [4]. In a final application, the MC beamlet generation method described in this thesis is implemented into a direct aperture optimization (DAO) algorithm. The implementation of MC beamlet generation in DAO forms the basis for a purely MC based inverse treatment planning system.

Modern image guided radiation therapy involves the use of an isocentrically mounted imaging system to take radiographs of a patient's position before the start of each treatment. Image guidance helps to minimize errors associated with a patients setup, but the radiation dose received by patients from imaging must be managed to ensure no additional risks. The Varian On-Board Imager (OBI) (Varian Medical Systems, Inc., Palo Alto, CA) does not have an automatic exposure control system and therefore requires exposure factors to be manually selected. Without patient specific exposure factors, images may become saturated and require multiple unnecessary exposures. A software based automatic exposure control system has been developed to predict optimal, patient specific exposure factors. The OBI system was modelled in terms of the x-ray tube output and detector response in order to calculate the level of detector saturation for any exposure situation. Digitally reconstructed radiographs are produced via ray-tracing through the patients' volumetric datasets that are acquired for treatment planning. The ray-trace determines the attenuation of the patient and subsequent x-ray spectra incident on the imaging detector. The resulting spectra are used in the detector response model to determine the exposure levels required to minimize detector saturation. Images calculated for various phantoms showed good agreement with the images that were acquired on the OBI. Overall, regions of detector saturation were accurately predicted and the detector response for non-saturated regions in images of an anthropomorphic phantom were calculated to generally be within 5 to 10 % of the measured values. Calculations were performed on patient data and found similar results as the phantom images, with the calculated images being able to determine detector saturation with close agreement to images that were acquired during treatment. Overall, it was shown that the system model and calculation method could potentially be used to predict patients' exposure factors before their treatment begins, thus preventing the need for multiple exposures. / Graduate / 0760 / 0574 / 0756

Radiation therapy (RT) plays a crucial role in the management of cancer, however, current standards of care have yet to account for patient specific radiation sensitivity. Raman spectroscopy (RS) is a promising technique for radiobiological studies as a way to measure radiation responses in biological samples and could provide a method for monitoring and predicting radiation response in patients. The work in this dissertation gives way to significant advances in the implementation of RS for applications in radiation oncology. Specifically, instrumentation improvements for clinical implementation of RS were achieved through the investigation and development of Raman microfluidic systems. Unique magnesium fluoride based microfluidic systems were engineered and evaluated for applications in radiobiological studies. These systems were found to yield superior spectral quality over traditional microfluidic designs. Furthermore, in order to assert RS as a key technique for clinical monitoring and prediction of radiation responses, human non-small cell lung cancer (NSCLC) and breast adenocarcinoma tumour xenograft models were investigated for Raman signatures of radiation response. These studies found that RS can identify unique and distinct signatures of radiation response in tumours, that can be tracked over time. In particular, NSCLC tumours were found to have key radiation induced modulations in cell cycle and metabolic linked spectral features- including glycogen. Breast adenocarcinoma tumours were found to exhibit distinct fluctuations in spectral features linked to cell cycle as well as protein content. In the case of NSCLC, radiation response signatures were found to be linked to tumour regression and hypoxic status of the tumour- a key factor that dictates radiation resistance in the disease. This work provides the first application of RS to measure radiation response signatures of tumours irradiated \textit{in vivo}. These results show that RS is a versatile technique that can offer insight into radiation induced molecular changes that are unique to the type of cancer and can be monitored over several days following radiation exposure. Together with improved instrumentation for radiobiological studies using microfluidics, the work presented in this dissertation further emphasizes the key role RS can have in radiation oncology and personalization of RT. / Graduate / 2019-08-21

La radiothérapie moderne combine les techniques complexes et les traitements personnalisés, avec le risque que certaines évolutions et erreurs ayant lieu au cours de traitement passent inaperçues. Ces aléas peuvent entraîner des conséquences graves pour la santé du patient. Dans cette perspective, nous avons étudié le potentiel d'un système de dosimétrie in vivo de transit pour le suivi continu du patient et, par conséquent, la radiothérapie adaptative. L'expérience clinique et des tests de faisabilité ont permis de définir les axes de travail principaux: l'automatisation et la simplification du procédé d'analyse des contrôles. Les développements incluent la création d'une bibliothèque de données standard et une série d'analyses de causes racines, permettant ainsi de renforcer la précision du système, d'améliorer l'automatisation de sa mise en place et d'identifier des pistes pour une analyse efficace des résultats et pour la création d'outils supplémentaires facilitant le suivi et l'adaptation du traitement en routine clinique. / Modern radiation therapy combines complex techniques and personalized treatments, with the risk that certain evolutions and errors occurring during the course of the treatment might go unnoticed. These fluctuations may cause great damage to the health of the patient. In this perspective, we worked on the potential of a transit in vivo dosimetry system for continuous monitoring of the patient and, hereafter, adaptive radiotherapy. Our clinical experience and feasibility testing determined the main lines of work : automatization and simplification of the results analysis method. The developments included the creation of a golden data library and a series of root cause analyzes, allowing us to strengthen the accuracy of the system, to enhance the automatization of the setup and to identify tracks for an efficient analysis of the results and for the creation of additional analytical tools to facilitate the monitoring and adaptation of the treatments in clinical routine.

No Brasil, para fins de planejamento de barreiras físicas em instalações radiográficas ou para a verificação dos níveis de restrição de dose em levantamentos radiométricos, deve ser usada a grandeza operacional equivalente de dose ambiente. Na prática, os monitores de radiação utilizados em proteção radiológica apresentam suas leituras na grandeza dosimétrica kerma no ar. Portanto, é preciso utilizar um coeficiente que converta esta grandeza dosimétrica na grandeza operacional recomendada. As normas nacionais estabelecem que o coeficiente de conversão no valor de 1,14 Sv/Gy deve ser usado para realizar esta operação, desconsiderando a diferença na distribuição espectral dos fótons dos feixes de raios X comumente encontrados em salas de radiologia convencional. O presente trabalho tem por objetivo determinar os coeficientes de conversão considerando a distribuição espectral da radiação secundária e secundária transmitida através de placas de argamassa baritada. Para atingir os objetivos propostos, foi desenvolvida uma metodologia experimental para as medições dos espectros das radiações secundárias e secundárias transmitidas usando um sistema espectroscópico com detector de CdTe e uma câmara de ionização de 1800 cm3. A região torácica de um objeto simulador antropomórfico, RANDO® Man, foi usada como região espalhadora. Foram utilizadas tensões no tubo entre 40 kV e 150 kV com intervalos na tensão de 10 kV. Os ângulos de espalhamento foram de 30°, 60°, 90° 120° e 150° em relação ao eixo do feixe primário. Como atenuador da radiação secundária foram utilizadas placas de argamassa baritada com espessuras de aproximadamente 10, 15, 20 e 25 mm. Os resultados mostram que, para a radiação secundária, os coeficientes de conversão são maiores que o valor estabelecido no Brasil. Num exemplo típico de levantamento radiométrico, a estimativa do equivalente de dose ambiente determinado usando o coeficiente de conversão calculado a partir dos espectros resultou em um valor cerca de 40 % superior ao equivalente de dose ambiente calculado a partir do coeficiente adotado pela norma nacional. / In Brazil, for planning purposes of the physical barriers in a radiographic installation and for levels verification of dose restriction in radiometric surveys, the ambient dose equivalent operational quantity should be used. In practice, radiation monitors used in radiation protection, are calibrated in dosimetry quantity air kerma. Therefore, it is important to use a conversion coefficient, which turns this dosimetric quantity into a recommended operational quantity. The rules followed in Brazil still establish that the value of the conversion coefficient, 1.14 Sv/Gy, must be used in area monitoring, disregarding differences between the beam types with different photon spectral distribution, commonly found in conventional radiology rooms. Consequently, this work aims to determine the conversion coefficients considering the spectral distribution of the secondary radiation and secondary-transmitted radiation through barium mortar plates. To achieve the proposed objectives, it has been developed an experimental method for measurement of secondary and secondary transmitted spectra using a spectroscopic system with CdTe detector and an ionization chamber 1800 cm3. The thoracic region of an anthropomorphic phantom, RANDO® Man, was used as a scatter region. The voltages used began 40 kV up to 150 kV in displacements of 10 kV, the scattering angles were 30°, 60°, 90° 120° and 150° with respect to the axis of the primary beam. As attenuator object of the secondary radiation was used barium mortar plates with thicknesses of 10, 15, 20 and 25 mm approximately. The results show that for the secondary radiation, the conversion coefficients are greater than the value set in Brazil. In a typical example of radiometric survey, the estimated ambient dose equivalent using the conversion coefficient calculated from the spectra, is a 40% higher compared to the value obtained using the coefficient recommended in Brazil.