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Orientador: Joel Mesa Hormaza / Banca: Hélio Yoriyaz / Banca: Paulo de Tarso Siqueira / Resumo: O tratamento do câncer através da irradiação com prótons tem se desenvolvido a amplamente, de maneira que a cada década o número de centros com essa tecnologia aumenta progressivamente. Entretanto, o planejamento da rotina de terapia ainda é realizado com imagens de raios-X, que pode causar incertezas quanto ao posicionamento preciso do feixe de prótons sobre o tumor devido à diferença de comportamento ao interagir com a matéria. Por isso, são necessários estudos que busquem o aprimoramento da tomografia computadorizada com prótons, que tem como principal função, determinar a posição do pico de Bragg com eficiência. Mas para se desenvolver essa técnica é preciso determinar a trajetória exata que a partícula percorre dentro do corpo do paciente, que é possível com simulações baseadas no método de Monte Carlo. Vários programas no mercado utilizam Monte Carlo para diferentes tipos de propósitos, dentre os que são voltados para o transporte do próton, estão: GEANT, FLUKA e MCNPX. Esse último foi o utilizado neste trabalho para avaliar a perturbação no feixe incidente de prótons em um meio heterogêneo, composto por água e material simulador de osso compacto (interfaces perpendiculares ao feixe). Além de um modelo formado por água e PMMA (interfases paralelas ao feixe) para avaliar o uso de fantomas desses materiais. Foram estudadas energia, posição e ângulo de saída dos prótons considerando somente partículas primárias e também para todas as partículas / Abstract: Cancer treatment by irradiation with protons has been widely developed so that each decade the number of centers based on this technology increases progressively. However, the planning of routine therapy is performed with images of X- rays, which can cause uncertainties as to the precise positioning of the proton beam on the tumor due to the difference in behavior when interacting with matter. Therefore, it is necessary studying the improvement of computed tomography with protons, whose main function, determine the position of the Bragg peak efficiently. Nevertheless, to develop this technique it is necessary to determine the exact path that the particle travels through the patient's body, which is possible with simulations based on Monte Carlo method. There are several programs that use Monte Carlo for different types of purposes, among which are meant for the transport of the proton: GEANT, FLUKA and MCNPX. The third one was used in this work to evaluate the disturbance in the incident beam of protons in a heterogeneous medium composed of water and equipment simulator compact bone (beam direction perpendicular to the interface) and water-PMMA (beam parallel to the interface). The output energy, position and angle of the protons were studied considering only primary particles and for all particles / Mestre

Les travaux effectués au cours de cette thèse ont été réalisés dans le cadre du développement d'une plateforme d'irradiation protons dédiée aux études en radiobiologie (Radiograaff) à partir de l'accélérateur Van de Graaff 4 MV de l'Institut de Physique Nucléaire de Lyon. Ceci, grâce à une collaboration étroite et interdisciplinaire entre les physiciens et ingénieurs de l'Institut de Physique Nucléaire de Lyon (IPNL) et des biologistes du Laboratoire de Radiobiologie Cellulaire et Moléculaire (LRCM) du CHU de Lyon Sud. Afin de présenter le développement de la plateforme Radiograaff, ce manuscrit se découpera en trois chapitres. Le premier chapitre présente les fondements de l'hadronthérapie et le contexte scientifique du projet. Nous traiterons, dans une première partie, de l'interaction ions-matière vivante afin de mieux cerner les concepts théoriques associés à l'hadronthérapie. Et nous présenterons, dans un second temps, les intérêts scientifiques et les objectifs du projet Radiograaff. Le deuxième chapitre concernera les développements instrumentaux de la ligne d'irradiation. Après avoir discuté du mode de délivrance et d'extraction du faisceau ainsi que des méthodes de simulation que nous avons employées pour le dimensionnement théorique la ligne d'irradiation, nous présenterons le système de contrôle de la dosimétrie. Le chapitre 2 sera conclu par les résultats de l'évaluation et de la qualification de la plateforme. Enfin, dans le troisième chapitre, après une brève présentation de quelques aspects de biologie et de radiobiologie, nous présenterons les premiers résultats obtenus concernant l'efficacité biologique relative des protons délivrés par la plateforme Radiograaff. Nous discuterons des protocoles, des conditions expérimentales ainsi que des méthodes d'analyse des résultats / The work done in this thesis has been made in the development of a proton irradiation platform dedicated for radiobiological studies from the 4 MV Van de Graaff accelerator of the Institut de Physique Nucléaire de Lyon (IPNL). These developments have been made through a close interdisciplinary collaboration between physicists and engineers from IPNL and biologists from the Laboratoire de Radiobiologie Cellulaire et Moléculaire (LRCM, CHU Lyon Sud). To present the development of Radiograaff platform, this manuscript will split into three chapters. The first chapter introduces the basics of hadrontherapy and the scientific context of the project. In the first part of this chapter, we present the interactions between ion and matter in order to better understand the theoretical concepts associated with the hadrons. Then, we present the scientific interests and objectives of the Radiograaff project. The second chapter concerns the instrumental developments of the beam line. After discussing the delivery mode and beam extraction in air and simulation methods that we used to design the theoretical line radiation, we present the dosimetric monitoring system. The chapter 2 is concluded by the results of the evaluation and qualification of the platform. Finally, in the third chapter, after a brief presentation of some aspects of biology and radiobiology, we present the first results on the relative biological effectiveness of protons delivered by the Radiograaff platform. We discuss the protocols, experimental conditions and methods for analysing results

The interest in the role of the solar wind termination shock (TS) and heliosheath in cosmic ray (CR) modulation studies has increased sigm6cantly as the Voyager 1 and 2 spacecraft approach the estimated position of the TS. For this work the modulation of galactic CR protons, anti-protons, electrons with a Jovian source, positrons, Helium, and anomalous protons and Helium, and the consequent charge-sign dependence, are studied with an improved and extended two-dimensional numerical CR modulation model including a TS with diffusive shock acceleration, a heliosheath and drifts. The modulation is computed using improved local interstellar spectra (LIS) for almost all the species of interest to this study and new fundamentally derived diffusion coefficients, applicable to a number of CR species during both magnetic polarity cycles of the Sun. The model also allows comparisons of modulation with and without a TS and between solar minimum and moderate maximum conditions. The modulation of protons and Helium with their respective anomalous components are also studied to establish the consequent charge-sign dependence at low energies and the influence on the computed p/p, e-/p, and e-/He. The level of modulation in the simulated heliosheath, and the importance of this modulation 'barrier' and the TS for the different species are illustrated. From the computations it is possible to estimate the ratio of modulation occurring in the heliosheath to the total modulation between the heliopause and Earth for the mentioned species. It has been found that the modulation in the heliosheath depends on the particle species, is strongly dependent on the energy of the CRs, on the polarity cycle and is enhanced by the inclusion of the TS. The computed modulation for the considered species is surprisingly different and the heliosheath is important for CR modulation, although 'barrier' modulation is more prominent for protons, anti-protons and Helium, while the heliosheath cannot really be considered a modulation 'barrier' for electrons and positrons above energies of ~150 MeV. The effects of the TS on modulation are more pronounced for polarity cycles when particles are drifting primarily in the equatorial regions of the heliosphere along the heliospheric current sheet to the Sun, e.g. the A < 0 polarity cycle for protons, positrons, and Helium, and the A > 0 polarity cycle for electrons and anti-protons. This study also shows that the proton and Helium LIS may not be known at energies <~ 200 MeV until a spacecraft actually approaches the heliopause because of the strong modulation that occurs in the heliosheath, the effect of the TS, and the presence of anomalous protons and Helium. For anti-protons, in contrast, these effects are less pronounced. For positrons, with a completely different shape LIS, the modulated spectra have very mild energy dependencies <~ 300 MeV, even at Earth, in contrast to the other species. These characteristic spectral features may be helpful to distinguish between electron and positron spectra when they are measured near and at Earth. These simulations can be of use for future missions to the outer heliosphere and beyond. / Thesis (Ph.D. (Physics))--North-West University, Potchefstroom Campus, 2004.

The interest in the role of the solar wind termination shock (TS) and heliosheath in cosmic ray (CR) modulation studies has increased sigm6cantly as the Voyager 1 and 2 spacecraft approach the estimated position of the TS. For this work the modulation of galactic CR protons, anti-protons, electrons with a Jovian source, positrons, Helium, and anomalous protons and Helium, and the consequent charge-sign dependence, are studied with an improved and extended two-dimensional numerical CR modulation model including a TS with diffusive shock acceleration, a heliosheath and drifts. The modulation is computed using improved local interstellar spectra (LIS) for almost all the species of interest to this study and new fundamentally derived diffusion coefficients, applicable to a number of CR species during both magnetic polarity cycles of the Sun. The model also allows comparisons of modulation with and without a TS and between solar minimum and moderate maximum conditions. The modulation of protons and Helium with their respective anomalous components are also studied to establish the consequent charge-sign dependence at low energies and the influence on the computed p/p, e-/p, and e-/He. The level of modulation in the simulated heliosheath, and the importance of this modulation 'barrier' and the TS for the different species are illustrated. From the computations it is possible to estimate the ratio of modulation occurring in the heliosheath to the total modulation between the heliopause and Earth for the mentioned species. It has been found that the modulation in the heliosheath depends on the particle species, is strongly dependent on the energy of the CRs, on the polarity cycle and is enhanced by the inclusion of the TS. The computed modulation for the considered species is surprisingly different and the heliosheath is important for CR modulation, although 'barrier' modulation is more prominent for protons, anti-protons and Helium, while the heliosheath cannot really be considered a modulation 'barrier' for electrons and positrons above energies of ~150 MeV. The effects of the TS on modulation are more pronounced for polarity cycles when particles are drifting primarily in the equatorial regions of the heliosphere along the heliospheric current sheet to the Sun, e.g. the A < 0 polarity cycle for protons, positrons, and Helium, and the A > 0 polarity cycle for electrons and anti-protons. This study also shows that the proton and Helium LIS may not be known at energies <~ 200 MeV until a spacecraft actually approaches the heliopause because of the strong modulation that occurs in the heliosheath, the effect of the TS, and the presence of anomalous protons and Helium. For anti-protons, in contrast, these effects are less pronounced. For positrons, with a completely different shape LIS, the modulated spectra have very mild energy dependencies <~ 300 MeV, even at Earth, in contrast to the other species. These characteristic spectral features may be helpful to distinguish between electron and positron spectra when they are measured near and at Earth. These simulations can be of use for future missions to the outer heliosphere and beyond. / Thesis (Ph.D. (Physics))--North-West University, Potchefstroom Campus, 2004.

Thesis--University of California, Berkeley. / Includes bibliographical references (p. 57). 23

Cette thèse explore les conséquences du fait que les sources de rayons cosmiques sont distribuées de façon non homogène dans notre Galaxie. Elle débute par plusieurs synthèses théoriques et expérimentales. Dans un premier temps la présentation du milieu interstellaire permet de comprendre les mécanismes en jeu dans la propagation et l'accélération des rayons cosmiques. Puis l'étude du mécanisme détaillé de la diffusion des rayons cosmiques sur le champ magnétique conduit à l'équation de propagation utilisée communément. Les solutions stationnaires de cette équation seront rappelées, puis la thèse s'articule autour de l'étude des solutions non stationnaires dans le cadre de sources ponctuelles dépendantes du temps. Une étude statistique permet d'évaluer la dispersion du flux de rayons cosmiques autour de sa valeur moyenne. Le calcul de cette dispersion conduite à des divergences mathématiques et des outils statistiques sont développés pour contourner ce problème. Ainsi l'effet de la granularité des sources est discuté et l'impact sur le spectre du rayonnement cosmique permet d'expliquer les récentes mesures de flux de protons et d'héliums de expériences CREAM et PAMELA.D'autre part la thèse porte sur l'étude de l'anisotropie du rayonnement cosmique. Les méthodes de mesures expérimentales seront rappelées, et une partie du manuscrit est consacrée à relier les calculs théoriques, menés dans le cadre des modèles de propagation, aux expériences. S'en suit d'une part le calcul de l'effet de l'environnement local sur la mesure d'anisotropie, comme l'influence d'un coefficient de diffusion local. Puis, l'anisotropie et sa variance sont calculées dans le cadre de sources ponctuelles avec l'aide des outils développés dans la première partie. Enfin, la possible influence des sources locales sur l'anisotropie est discutée à la lumière des derniers résultats expérimentaux. / In this thesis I study the consequence of non homogeneously distributed cosmic ray sources in the Milky way. The document starts with theoretical and experimental synthesis. Firstly, I will describe the interstellar medium to understand the mechanism of propagation and acceleration of cosmic rays. Then, the detailed study of cosmic rays diffusion on the galactic magnetic field allows to write a commonly used propagation equation. I will recall the Steady-state solutions of this equation, then I will focus on the time dependant solutions with point-like sources. A statistical study is performed in order to estimate the standard deviation of the flux around its mean value. The computation of this standard deviation leads to mathematical divergences. Thus, I will develop statistical tools to bypass this issue. So i will discuss the effect of the granularity of cosmic ray sources. Its impact on cosmic ray spectrum can explain some recent features observed by the experiments CREAM and PAMELA.Besides, this thesis is focused on the study of the anisotropy of cosmic rays. I will recap experimental methods of measurements, and I will show how to connect theoretical calculation from propagation theories to experimental measurements. Then, the influence of the local environment on the anisotropy measurements will be discussed, particularly the effect of a local diffusion coefficient. Then, I will compute anisotropy and its variance in a framework of point-like local sources with the tools developed in the first part. Finally, the possible influence of local sources on the anisotropy is discussed in the light of the last experimental results.

Made available in DSpace on 2014-08-13T14:50:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-25Bitstream added on 2014-08-13T17:59:54Z : No. of bitstreams: 1 000769599_20160131.pdf: 256213 bytes, checksum: 5f511cbb596c1f707bc977be42246aaf (MD5) Bitstreams deleted on 2016-02-01T10:15:56Z: 000769599_20160131.pdf,. Added 1 bitstream(s) on 2016-02-01T10:16:46Z : No. of bitstreams: 1 000769599.pdf: 1800159 bytes, checksum: 4ba8b1a044e20855baf40d195fdc0c91 (MD5) Bitstreams deleted on 2016-06-15T18:56:31Z: 000769599_sub.pdf,. Added 1 bitstream(s) on 2016-06-15T18:57:10Z : No. of bitstreams: 1 000769599.pdf: 18986432 bytes, checksum: a3924b26321cd155af0495154ed8096f (MD5) / O tratamento do câncer através da irradiação com prótons tem se desenvolvido a amplamente, de maneira que a cada década o número de centros com essa tecnologia aumenta progressivamente. Entretanto, o planejamento da rotina de terapia ainda é realizado com imagens de raios-X, que pode causar incertezas quanto ao posicionamento preciso do feixe de prótons sobre o tumor devido à diferença de comportamento ao interagir com a matéria. Por isso, são necessários estudos que busquem o aprimoramento da tomografia computadorizada com prótons, que tem como principal função, determinar a posição do pico de Bragg com eficiência. Mas para se desenvolver essa técnica é preciso determinar a trajetória exata que a partícula percorre dentro do corpo do paciente, que é possível com simulações baseadas no método de Monte Carlo. Vários programas no mercado utilizam Monte Carlo para diferentes tipos de propósitos, dentre os que são voltados para o transporte do próton, estão: GEANT, FLUKA e MCNPX. Esse último foi o utilizado neste trabalho para avaliar a perturbação no feixe incidente de prótons em um meio heterogêneo, composto por água e material simulador de osso compacto (interfaces perpendiculares ao feixe). Além de um modelo formado por água e PMMA (interfases paralelas ao feixe) para avaliar o uso de fantomas desses materiais. Foram estudadas energia, posição e ângulo de saída dos prótons considerando somente partículas primárias e também para todas as partículas / Cancer treatment by irradiation with protons has been widely developed so that each decade the number of centers based on this technology increases progressively. However, the planning of routine therapy is performed with images of X- rays, which can cause uncertainties as to the precise positioning of the proton beam on the tumor due to the difference in behavior when interacting with matter. Therefore, it is necessary studying the improvement of computed tomography with protons, whose main function, determine the position of the Bragg peak efficiently. Nevertheless, to develop this technique it is necessary to determine the exact path that the particle travels through the patient's body, which is possible with simulations based on Monte Carlo method. There are several programs that use Monte Carlo for different types of purposes, among which are meant for the transport of the proton: GEANT, FLUKA and MCNPX. The third one was used in this work to evaluate the disturbance in the incident beam of protons in a heterogeneous medium composed of water and equipment simulator compact bone (beam direction perpendicular to the interface) and water-PMMA (beam parallel to the interface). The output energy, position and angle of the protons were studied considering only primary particles and for all particles