Les doses secondaires neutroniques ne sont actuellement pas estimées lors de la planification de traitement dans les centres de protonthérapie puisque les logiciels de planification de traitement (TPS) ne le proposent pas tandis que les simulations Monte Carlo (MC) et les mesures sont inadaptées pour un environnement clinique. L’objectif de la thèse est de développer un modèle analytique dédié à l’estimation des doses secondaires neutroniques aux organes sains qui reste pratique et simple d’utilisation en routine clinique. Dans un premier temps, la géométrie existante de la gantry installée au Centre de protonthérapie d’Orsay (CPO) de l’institut Curie modélisée avec le code de calcul MCNPX a été étendue à trois configurations de traitement supplémentaires (énergie en entrée de ligne de 162, 192 et 220 MeV). Une approche comparative simulation-mesure a ensuite été entreprise afin de vérifier la capacité de ces modélisations à reproduire les distributions de doses (en profondeur et latérales) des protons primaires ainsi que le champ secondaire neutronique. Des écarts inférieurs à 2 mm ont été observés pour les protons primaires. Pour les neutrons secondaires, les écarts sont plus mitigés avec des rapports simulation sur mesure de ~2 et de ~6, respectivement pour la spectrométrie et les équivalents de dose dans un fantôme physique. L’analyse des résultats a permis d’identifier l’origine de ces écarts et de mettre en perspective la nécessité de conduire de nouvelles études pour améliorer à la fois les mesures expérimentales et les simulations MC. Dans un deuxième temps, une approche purement numérique a été considérée pour calculer les doses neutroniques aux organes sains de fantômes voxélisés représentant des patients d’un an, de dix ans et adulte, traités pour un craniopharyngiome. Une variation de chaque paramètre de traitement a été réalisée afin d’étudier leur influence respective sur les doses neutroniques. Ces paramètres ont pu être ordonnés par ordre décroissant d’influence : incidence de traitement, distance organe-collimateur et organe-champ de traitement, taille/âge des patients, énergie de traitement, largeur de modulation, ouverture du collimateur, etc. Des suggestions ont également été avancées pour réduire les doses neutroniques.Dans un troisième temps, un modèle analytique a été conçu de façon à être utilisable en routine clinique, pour tous les types de tumeur et toutes les installations de protonthérapie. Son entraînement séparé pour trois incidences de traitement a montré des écarts inferieurs à ~30% et ~60 µGy Gy⁻¹ entre les données d’apprentissage (doses neutroniques calculées aux organes sains) et les valeurs prédites par le modèle analytique. La validation a consisté à comparer les doses neutroniques estimées par le modèle analytique à celles calculées avec MCNPX pour des conditions différentes des données d’apprentissage. Globalement, un accord acceptable a été observé avec des écarts moyens de ~30% et ~100 µGy Gy⁻¹. La flexibilité et la fiabilité du modèle analytique ont ainsi été mises en évidence. L’entraînement du modèle analytique à partir d’équivalents de dose neutroniques mesurés dans un fantôme solide au Centre Antoine Lacassagne a confirmé son universalité, bien qu’il requière néanmoins quelques ajustements supplémentaires pour améliorer sa précision. / Stray neutron doses are currently not evaluated during treatment planning within proton therapy centers since treatment planning systems (TPS) do not allow this feature while Monte Carlo (MC) simulations and measurements are unsuitable for routine practice. The PhD aims at developing an analytical model dedicated to the estimation of stray neutron doses to healthy organs which remains easy-to-use in clinical routine. First, the existing MCNPX model of the gantry installed at the Curie institute - proton therapy center of Orsay (CPO) was extended to three additional treatment configurations (energy at the beam line entrance of 162, 192 and 220 MeV). Then, the comparison of simulations and measurements was carried out to verify the ability of the MC model to reproduce primary proton dose distributions (in depth and lateral) as well as the stray neutron field. Errors within 2 mm were observed for primary protons. For stray neutrons, simulations overestimated measurements by up to a factor of ~2 and ~6 for spectrometry and dose equivalent in a solid phantom, respectively. The result analysis enabled to identify the source of these errors and to put into perspective new studies in order to improve both experimental measurements and MC simulations. Secondly, MC simulations were used to calculate neutron doses to healthy organs of a one-year-old, a ten-year-old and an adult voxelized phantoms, treated for a carniopharyngioma. Treatment parameters were individually varied to study their respective influence on neutron doses. Parameters in decreasing order of influence are: beam incidence, organ-to-collimator and organ-to-treatment field distances, patient’ size/age, treatment energy, modulation width, collimator aperture, etc. Based on these calculations, recommendations were given to reduce neutron doses. Thirdly, an analytical model was developed complying with a use in clinical routine, for all tumor localizations and proton therapy facilities. The model was trained to reproduce calculated neutron doses to healthy organs and showed errors within ~30% and ~60 µGy Gy⁻¹ between learning data and predicted values; this was separately done for each beam incidence. Next, the analytical model was validated against neutron dose calculations not considered during the training step. Overall, satisfactory errors were observed within ~30% and ~100 µGy Gy⁻¹. This highlighted the flexibility and reliability of the analytical model. Finally, the training of the analytical model made using neutron dose equivalent measured in a solid phantom at the center Antoine Lacassagne confirmed its universality while also indicating that additional modifications are required to enhance its accuracy.

<p>Elevated blood pressure (BP) is a significant risk factor for cardiovascular diseases (CVD), which are the leading cause of morbidity and mortality. Dietary minerals such as sodium (Na) and potassium (K) play a crucial role in overall health and play a specific function in regulating blood pressure in the human body. Numerous studies have been conducted on the association between blood pressure and dietary intervention. While many nutritional intervention studies have shown adverse effects of excessive Na intake and the beneficial impact of supplemental K in humans, less is understood on Na and K tissue retention and health outcomes of such retention. The most commonly used biomarkers to study Na retention and regulation is urine Na. However, the use of urine Na concentration as an indicator of Na retention has its limitations and has been recently questioned. In-vivo neutron activation analysis (IVNAA) is a unique and powerful technique for elemental analysis in the human body that has the potential to quantify Na and K retention and monitor their bio-kinetics. This research work designed an in vivo neutron irradiation system with high sensitivity and minimal radiation dose to measure Na/K and monitor Na/K bio-kinetics. The system was characterized, tested, and validated for K measurement in mice and rats. Moreover, we developed a methodology for in vivo quantification of Na in pigs in bone and soft tissue after dietary intervention. The project's overall goal is to exploit the potential of a compact DD neutron generator-based neutron activation analysis system for in vivo quantification of Na and K in humans and small animals.</p>

Proton therapy is a relatively new treatment modality for cancer, having recently been incorporated into hospitals in the last two decades. Although proton therapy has much higher start up and treatment costs than traditional methods of radiotherapy, it continues to expand in use today. One reason for this is that proton therapy has the advantage of a more precise localization of dose compared to traditional radiotherapy. Other proposed advantages of proton therapy in the treatment of cancer may lead to a faster expanse in its use if proven to be more effective than traditional radiotherapy. Therefore, much research must be done to investigate the possible negative and positive effects of using proton therapy as a treatment modality. In proton therapy, protons do account for the vast majority of dose. However, when protons travel through matter, secondary particles are created by the interactions of protons and matter en route to and within the patient. It is believed that secondary dose can lead to secondary cancer, especially in pediatric cases. Therefore, the focus of this work is determining both primary and secondary dose. In order to develop relevant simulations, the specifications of the treatment room and beam were based off of real-world facilities as closely as possible. Using available data from proton accelerators and clinical facilities, an accurate proton therapy nozzle was designed. Dose calculations were performed by MCNPX using a simple water phantom, and then beam characteristics were investigated to ensure the accuracy of the model. After validation of the beam nozzle, primary and secondary dose values were tabulated and discussed. By demonstrating the method of these calculations, the purpose of this work is to serve as a guide into the relatively recent field of Monte Carlo methods in proton therapy.

In the absence of a fusion neutron source, research on the structural integrity of materials in the fusion environment relies on current fission data and simulation methods. Through investigation of the Fe-Cr system, this detailed study explores the challenges and limitations in the use of currently available radiation sources for fusion materials research. An investigation of ion-irradiated Fe12%Cr using nanoindentation with a cube corner, Berkovich and spherical tip, and micro-cantilever testing with two different geometries, highlighted that the measurement of irradiation hardening was largely dependent on the type of test used. Selected methods were used for the comparison of Fe6%Cr irradiated by ions and neutrons to a dose of 1.7dpa at a temperature of 288&deg;C. Micro-cantilever tests of the Fe6%Cr alloy with beam depths of 400 to 7000nm, identified that size effects may significantly obscure irradiation hardening and that these effects are dependent on radiation conditions. Irradiation hardening in the neutron-irradiated alloy was approximately double that of the ion-irradiated alloy and exhibited increased work hardening. Similar differences in hardening were observed in an Fe5%Cr alloy after ion-irradiation to a dose of 0.6dpa at 400&deg;C and doses rates of 6 x 10^-4dpa/s and 3 x 10^-5dpa/s. Identified by APT, it was shown that increased irradiation hardening was likely to be caused by the enhanced segregation of Cr observed in the alloy irradiated with the lower dose rate. These observations have significant implications for future fusion materials research in terms of the simulation of fusion relevant radiation conditions and micro-mechanical testing.