Radiotherapy delivered using scanned beams of protons enables greater conformity between the dose distribution and the tumour than conventional radiotherapy using X rays. However, the dose distributions are more sensitive to changes in patient anatomy, and tend to deteriorate in the presence of motion. Online dose calculation during treatment delivery offers a way of monitoring the delivered dose in real time, and could be used as a basis for mitigating the effects of motion. The aim of this work has therefore been to investigate how the computational power offered by graphics processing units can be harnessed to enable fast analytical dose calculation for online monitoring in proton therapy. The first part of the work consisted of a systematic investigation of various approaches to implementing the most computationally expensive step of the pencil beam algorithm to run on graphics processing units. As a result, it was demonstrated how the kernel superposition operation, or convolution with a spatially varying kernel, can be efficiently implemented using a novel scatter-based approach. For the intended application, this outperformed the conventional gather-based approach suggested in the literature, permitting faster pencil beam dose calculation and potential speedups of related algorithms in other fields. In the second part, a parallelised proton therapy dose calculation engine employing the scatter-based kernel superposition implementation was developed. Such a dose calculation engine, running all of the principal steps of the pencil beam algorithm on a graphics processing unit, had not previously been presented in the literature. The accuracy of the calculation in the high- and medium-dose regions matched that of a clinical treatment planning system whilst the calculation was an order of magnitude faster than previously reported. Importantly, the calculation times were short, both compared to the dead time available during treatment delivery and to the typical motion period, making the implementation suitable for online calculation. In the final part, the beam model of the dose calculation engine was extended to account for the low-dose halo caused by particles travelling at large angles with the beam, making the algorithm comparable to those in current clinical use. By reusing the workflow of the initial calculation but employing a lower resolution for the halo calculation, it was demonstrated how the improved beam model could be included without prohibitively prolonging the calculation time. Since the implementation was based on a widely used algorithm, it was further predicted that by careful tuning, the dose calculation engine would be able to reproduce the dose from a general beamline with sufficient accuracy. Based on the presented results, it was concluded that, by using a single graphics processing unit, dose calculation using the pencil beam algorithm could be made sufficiently fast for online dose monitoring, whilst maintaining the accuracy of current clinical systems.

Spaceborne scatterometer instruments are important tools for the remote sensing of the Earth's environment. In addition to the primary goal of measuring ocean winds, data from scatterometers have proven useful in the study of a variety of land and cryopshere processes as well. Several satellites carrying scatterometers have flown in the last two decades. These previous systems have been "fan-beam" scatterometers, where multiple antennas placed in fixed positions are used. The fan-beam scatterometer approach, however, has disadvantages which limit its utility for future missions. An alternate approach, the conically-scanning "pencil-beam" scatterometer technique, alleviates many of the problems encountered with earlier systems and provides additional measurement capability. Due to these advantages, the pencil-beam approach has been selected by NASA as the basis for future scatterometer missions. Whereas the fan-beam approach is mature and well understood, there is need for a fundamental study of the unique aspects of the pencil-beam technique. In this dissertation, a comprehensive treatment of the design issues associated with pencil-beam scatterometers is presented. A new methodology is established for evaluating and optimizing the performance of conically-scanning radar systems. Employing this methodology, key results are developed and used in the design of the SeaWinds instrument - NASA's first pencil-beam scatterometer. Further, the theoretical framework presented in this study is used to propose new scatterometer techniques which will significantly improve the spatial resolution and measurement accuracy of future instruments.

Radiation therapy with light ions improves treatment outcome for a number of tumor types. The advantageous dose distributions of light ion beams en-able exceptional target conformity, which assures high dose delivery to the tumor while minimizing the dose to surrounding normal tissues. The demand of high target conformity necessitates development of accurate methods to calculate absorbed dose distributions. This is especially important for heavy charged particle irradiation, where the patient is exposed to a complex radia-tion field of primary and secondary ions. The presented approach combines accurate Monte Carlo calculations using the SHIELD-HIT07 code with a fast analytical pencil beam model, to pro-vide dose distributions of light ions. The developed model allows for ana-lytical descriptions of multiple scattering and energy loss straggling proc-esses of both primary ions and fragments, transported in tissue equivalent media. By applied parameterization of the radial spread of fragments, im-proved description of radial dose distributions at every depth is obtained. The model provides a fast and accurate tool of practical value in clinical work. Compared to conventional radiation modalities, an enhanced tissue response is seen after light ion irradiation and biological optimization calls for accu-rate model description and prediction of the biological effects of ion expo-sure. In a joint study, the performance of some radiobiological models is compared for facilitating the development towards more robust and precise models. Specifically, cell survival after exposure to various ion species is modeled by a fast analytical cellular track structure approach in conjunction with a simple track-segment model of ion beam transport. Although the stud-ies show that descriptions of complex biological effects of ion beams, as given by simple radiobiological models, are approximate, the models may yet be useful in analyzing clinical results and designing new strategies for ion therapy.

Cette thèse porte sur les dispositifs de contrôle de faisceaux de protons balayés. La société IBA (Ion Beam Applications), ayant besoin d'une d'unité moniteur pour équiper ses centres de protonthérapie dotés de la technologie Pencil Beam Scanning, a fait appel au groupe applications médicales du Laboratoire de Physique Corpusculaire de Caen. En 2008, ce groupe a alors réalisé, en collaboration avec IBA, une chambre d'ionisation, nommée IC2/3, destinée à équiper la tête d'irradiation universelle IBA dédiée au PBS. Ce détecteur vérifie que la fluence particulaire reste conforme à celle planifiée. Une partie du travail de thèse a consisté à caractériser cette unité moniteur sur une gamme d'énergie faisceau, de position faisceau et de débit de dose applicables en protonthérapie. Après une introduction sur la protonthérapie, la phase de validation d'IC/3 est exposée dans ce mémoire. Les informations fournies par cette unité moniteur permettent le contrôle du faisceau en termes de fluence particulaire mais n'assurent pas le contrôle qualité du traitement en termes de distribution spatiale de dose. La seconde partie du travail de thèse a donc été de concevoir un dispositif, toujours pour les faisceaux de protons balayés, capable de reconstruire la distribution spatiale de dose délivrée dans le patient au cours du traitement. L'élaboration de son cahier des charges est présentée dans ce mémoire ainsi que les diverses études de conception. Ce travail a permis de parvenir à un certain nombre de recommandations pour sa réalisation mais également à diverses perspectives de recherche.

L'étalonnage de l’image tomodensitométrique X en pouvoirs d’arrêt relatif est source d'incertitudes pour la planification du traitement en protontherapie. L’imagerie proton permettrait d’obtenir directement les pouvoirs d’arrêt ou les épaisseurs équivalent-eau tout en maîtrisant les incertitudes sur la planification du traitement. Ce travail vise à caractériser et optimiser les performances du système de tomographie proton proposé dans le cadre d’une nouvelle approche faisceau à faisceau, composé d’un trajectographe et d’un range meter. La position et la largeur du faisceau obtenues avec le trajectographe ainsi que la modélisation matricielle de la réponse du range meter par simulation Monte Carlo combinée à la déconvolution de la courbe de Bragg résiduelle ont permis de reconstruire l’épaisseur équivalent-eau traversée pour chaque faisceau. L’évaluation de la qualité des images a permis de montrer que la méthode de déconvolution permettait d’obtenir des images dépourvues d’artefacts et d’estimer le parcours du proton avec une précision de l’ordre de 0,7%. Le travail présenté dans cette thèse démontre la faisabilité d’un tel système d’imagerie. / Calibration of computed tomography image in relative stopping power is a source of uncertainties for the proton therapy treatment planning. Proton imaging could directly obtain stopping powers or equivalent water thicknesses and control uncertainties in the treatment planning. In the context of a new pencil beam approach, this work aims to characterize and optimize the performances of a proton tomography system consisting of a tracker and a range meter. Beam position and width obtained with the tracker and the range meter response matrix modelling by Monte Carlo simulation combined with the unfolding method of the residual Bragg curve enable to reconstruct the water equivalent thickness for each beam. The evaluation of the reconstructed images quality shows that images are artefact free and the proton range is estimated with 0.7% of accurancy by using the unfolding method. This thesis demonstrates the feasibility of such an imaging system.

The clinical introduction of proton therapy requires an extensive analysis of its benefits compared to conventional radiotherapy and a detailed analysis of possible uncertainties which might have serious consequences for patient treatment. In the first part of the presented thesis, the expected toxicities were evaluated for a treatment of head and neck cancer patients using a biologically adapted dose escalation schedule with photon and proton therapy. The feasibility of the dose escalation schedule could be demonstrated for both photon and proton therapy, since only a small increase in toxicity risk occurred for most toxicities. However, the expected toxicity risks were in most cases smaller with proton therapy. Furthermore, a higher benefit was found for patients with primary tumour locations in the upper head and neck area, who thus might be preferably referred to proton therapy. In the second part of this thesis, an extensive analysis of the impact of tumour motion in lung cancer treatment with active-scanning proton therapy was conducted. It could be shown, that dose degradations were small for tumour motion amplitudes below 5 mm. Parameters like the target volume concept, the optimisation approach, changes in the motion pattern and application sequence times had additional impact on the dose degradation. However, their magnitude was patient specific. Since not all parameters can be assessed before treatment, e.g. the motion pattern during treatment, prospective estimations should be supplemented by retrospective analyses. / Die Einführung der Protonentherapie in die klinische Praxis erfordert umfassende Analysen ihrer Vor- und Nachteile im Vergleich zur konventionellen Photonentherapie sowie detaillierte Untersuchungen der Auswirkungen von Unsicherheiten in der Therapieapplikation. Im ersten Teil der vorliegenden Arbeit wurden die zu erwartenden Nebenwirkungen bei der Behandlung von Patienten mit Kopf-Hals-Tumoren mit einem biologisch-adaptierten Fraktionierungsschema inklusive Dosiseskalation mit Photonen- und Protonentherapie evaluiert. Dabei konnte gezeigt werden, dass die Dosiseskalation sowohl mit Photonen- als auch Protonentherapie angewandt werden kann, da die Wahrscheinlichkeit für das Auftreten von Nebenwirkungen in den meisten Fällen kaum erhöht wurde. Weiterhin wurden die Nebenwirkungswahrscheinlichkeiten mit der Protonentherapie im Vergleich zur Photonentherapie reduziert. Dies war vor allem für Patienten mit Tumoren im oberen Kopf-Hals-Bereich der Fall. Diese könnten daher bevorzugt zur Protonentherapie überwiesen werden. Darüber hinaus wurde im zweiten Teil der Arbeit eine umfassende Analyse des Einflusses der Tumorbewegung auf die Dosisverteilung bei Behandlung von Lungentumoren mit aktiver Protonenstrahlformierung durchgeführt. Dabei zeigte sich, dass Dosisdegradierungen bei Bewegungsamplituden unter 5mm gering sind. Parameter wie das Zielvolumenkonzept, Veränderungen des Bewegungsmusters oder der Applikationszeiten nehmen zusätzlich Einfluss auf die Dosisdegradierung, allerdings in unterschiedlichem Maß für individuelle Patienten. Da nicht alle Parameter vor Behandlung bekannt sein können, sollten prospektive Dosisabschätzungen durch retrospektive Analysen ergänzt werden.

The clinical introduction of proton therapy requires an extensive analysis of its benefits compared to conventional radiotherapy and a detailed analysis of possible uncertainties which might have serious consequences for patient treatment. In the first part of the presented thesis, the expected toxicities were evaluated for a treatment of head and neck cancer patients using a biologically adapted dose escalation schedule with photon and proton therapy. The feasibility of the dose escalation schedule could be demonstrated for both photon and proton therapy, since only a small increase in toxicity risk occurred for most toxicities. However, the expected toxicity risks were in most cases smaller with proton therapy. Furthermore, a higher benefit was found for patients with primary tumour locations in the upper head and neck area, who thus might be preferably referred to proton therapy. In the second part of this thesis, an extensive analysis of the impact of tumour motion in lung cancer treatment with active-scanning proton therapy was conducted. It could be shown, that dose degradations were small for tumour motion amplitudes below 5 mm. Parameters like the target volume concept, the optimisation approach, changes in the motion pattern and application sequence times had additional impact on the dose degradation. However, their magnitude was patient specific. Since not all parameters can be assessed before treatment, e.g. the motion pattern during treatment, prospective estimations should be supplemented by retrospective analyses. / Die Einführung der Protonentherapie in die klinische Praxis erfordert umfassende Analysen ihrer Vor- und Nachteile im Vergleich zur konventionellen Photonentherapie sowie detaillierte Untersuchungen der Auswirkungen von Unsicherheiten in der Therapieapplikation. Im ersten Teil der vorliegenden Arbeit wurden die zu erwartenden Nebenwirkungen bei der Behandlung von Patienten mit Kopf-Hals-Tumoren mit einem biologisch-adaptierten Fraktionierungsschema inklusive Dosiseskalation mit Photonen- und Protonentherapie evaluiert. Dabei konnte gezeigt werden, dass die Dosiseskalation sowohl mit Photonen- als auch Protonentherapie angewandt werden kann, da die Wahrscheinlichkeit für das Auftreten von Nebenwirkungen in den meisten Fällen kaum erhöht wurde. Weiterhin wurden die Nebenwirkungswahrscheinlichkeiten mit der Protonentherapie im Vergleich zur Photonentherapie reduziert. Dies war vor allem für Patienten mit Tumoren im oberen Kopf-Hals-Bereich der Fall. Diese könnten daher bevorzugt zur Protonentherapie überwiesen werden. Darüber hinaus wurde im zweiten Teil der Arbeit eine umfassende Analyse des Einflusses der Tumorbewegung auf die Dosisverteilung bei Behandlung von Lungentumoren mit aktiver Protonenstrahlformierung durchgeführt. Dabei zeigte sich, dass Dosisdegradierungen bei Bewegungsamplituden unter 5mm gering sind. Parameter wie das Zielvolumenkonzept, Veränderungen des Bewegungsmusters oder der Applikationszeiten nehmen zusätzlich Einfluss auf die Dosisdegradierung, allerdings in unterschiedlichem Maß für individuelle Patienten. Da nicht alle Parameter vor Behandlung bekannt sein können, sollten prospektive Dosisabschätzungen durch retrospektive Analysen ergänzt werden.