Proton Compton scattering has been studied from 220 to 330 MeV at 90 degree center of mass scattering angle with the polarized photon beam at LEGS. Compton scattering is an important probe of the nucleon structure and its excited states. Polarization degrees of freedom reveal more information than unpolarized observables. This experiment measured, for the first time, the polarized cross sections of proton Compton scattering up to the Δ resonance. The parallel and perpendicular cross sections were measured at the same time. All the photons were tagged so that the energy dependent systematic errors are small. The measured unpolarized cross section is above the lower bound from unitary at all energies. The cross section asymmetry is obtained as a function of energy for the first time. The unpolarized cross section is compared with previous data and with calculations from the fixed-t dispersion model, the isobar model and the finite energy dispersion model. Although all these calculations agree fairly well with unpolarized cross section data, the photon asymmetry data show that the isobar model contains serious defects. The ratio of polarized cross sections, dσ_⫫/dσ_⟂, is compared with a model independent result. The results from the present experiment can be used in the calculation of the E2/M1 ratio in the N — Δ transition, which is an important signature of the tensor interaction between quarks. / Ph. D.

Traditionally, medical imaging techniques such as PET (positron emission tomography) and SPECT (single-photon emission computed tomography) have relied on mechanical collimators to detect the sources of photons. This limits the image's resolution and field of view. To improve upon this, Compton cameras have emerged as a promising alternative. The principle is to measure the angle of a photon scattered in the detector, which indicates the likely sources in the form of a cone culminating in the position of the interaction. The cones from multiple events may be superimposed in order to generate an image. The object of this work is to use list-mode likelihood methods to better reconstruct the source image from the data recorded by a simulated Compton camera in the case of a solid detector volume with good spatial- and energy resolution.  The results demonstrate an improvement of image quality for reconstructions of single point source and multiple extended sources. In addition, the results indicate that our used algorithm converges for point sources. The minimum number of measured events for accurate reconstruction for different source distributions remains to be determined, and the algorithm's ability to resolve closely adjacent sources should be investigated more.

Die Grundlage vieler zukünftiger Flüssigszintillator-Neutrinoexperimente (SNO+, Daya Bay, LENA) ist das Lösungsmittel Lineare-Alkyl-Benzene (LAB, C6H5CnH2n+1, n = 10 - 13). Zusammen mit dem weit verbreiteten Szintillator 2,5-Diphenyloxazole (PPO) ist es ein farb- und geruchsloses Detektormaterial mit hohem Flammpunkt. Im Vergleich zu toluol- oder xylolbasierten Szintillatoren ist LAB+PPO preiswert und nicht gesundheitsschädlich. Die Eigenschaften von LAB machen es ebenfalls interessant für die Anwendung an nELBE, die Neutronenfugzeitanlage im Helmholtz-Zentrum Dresden - Rossendorf. Ein neuer Ansatz zur Bestimmung der Lichtausbeute im niederenergetischen Bereich (bis 2 MeV) wird vorgestellt. Kombiniert wurden Messungen mit (quasi) monoenergetischen Gammastrahlungs-Prüfstrahlern und einem in dieser Arbeit aufgebauten Compton-Spektrometer. Letzteres ermöglicht die Bestimmung der Lichtausbeute bis zu 5 keVee. Der Birks-Parameter wurde für eine Lösung von LAB + 3 g/l PPO sowie für den Flüssigszintillator NE-213 bestimmt. Die relative Lichtausbeute in Bezug auf letzteren konnte mit diesen Messmethoden ebenfalls ermittelt werden. Zur spektralen Analyse des Lumineszenzlichtes wurden Messungen an Fluoreszenz- und UV/VIS- Spektrometern durchgeführt. Die Pulsformdiskriminationsfähigkeit auf LAB basierenden Szintillatoren wurde während eines Flugzeitexperiments in einem gemischten n-gamma-Feld eines Cf(252)-Prüfstrahlers ermittelt. Dabei kamen unterschiedliche Algorithmen der semi-analogen und digitalen Pulsformdiskrimination zum Einsatz. / Linear alkyl benzene (LAB, C6H5CnH2n+1, n = 10 - 13) is the proposed solvent for the SNO+, the Daya Bay Neutrino and LENA experiment. In solution with the commonly used scintillator PPO it is a colourless, odourless and cheap liquid scintillator with a high fash point and low health hazard compared to toluene based ones. The properties of LAB make this scintillator interesting also for nELBE, the neutron time-of-fight facility at Helmholtz-Zentrum Dresden - Rossendorf. A new approach to measure the light yield in the low-energy range using a combination of quasi-monoenergetic photon sources and a Compton-spectrometer is described. The latter allows the measurement of the light yield down to 5 keVee (electron equivalent). The Birks- Parameter was determined for a homemade solution (LAB + 3 g/l PPO) and for NE-213. The light yield (relative to this standard scintillator) was confrmed by measurements using a fuorescence spectrometer. The ability of pulse-shape-discrimination in a mixed n-gamma- field of a Cf(252) source was tested using different digital and semi-analogue techniques.

A dissertação pode ser dividida em duas partes: a primeira contém uma adaptação do modelo fenomenológico de Einstein conhecido como \"método dos coeficientes A e B\". As modificações são feitas no contexto da Eletrodinâmica Estocástica, uma teoria na qual as flutuações de ponto zero do campo eletromagnético são consideradas reais e clássicas. Nós obtemos, num estudo não relativístico e clássico, relações entre a energia e momento de partículas livres e a frequência da radiação transferida. Estas relações coincidem com as bem conhecidas relações que representam a conservação do quadrivetor momento-energia em espalhamento fóton-elétron. Na segunda parte nós tentamos descrever, de uma maneira qualitativa, o efeito Compton no espírito da Eletrodinâmica Estocástica. Encontramos indicações de que a ação combinada da força da reação da radiação e das flutuações de ponto zero é capaz de conferir à partícula carregada uma alta velocidade de recuo, e verificamos que a mesma é justamente a necessária para explanar o deslocamento da frequência observado como sendo devido ao efeito Doppler. Também calculamos a seção de choque diferencial para o espalhamento de radiação e encontramos a mesma expressão obtida por Compton no seu trabalho fundamental de 1923. / The dissertation may be divided in two parts: the first one contains an adaptation of Einstein\'s phenomenological model known as \"method of coefficients A and B\". The modifications are done in the framework of Stochastic Electrodynamics, a theory in wich the zero point fluctuations of the electromagnetic field are considered real and classical. We obtain, in a nonrelativistic and Classical approach, relations among the energy and momentum of free particles and the frequency of the exchanged radiation. These relations are coincident with the well known ones who depict the four-momentum conservation in photon-electron scattering. In the second part, we try to describe, in a qualitative manner, the Compton scattering in the spirit of Stochastic Electrodynamics. We find indications that the combined action of the radiation reaction force and the zero point flutuating field are able to give the charged particle a high recoil velocity, and we verify this one is just the necessary to explain the frequency shift as due to a double Doppler shift. We also calculate the differential cross section for the radiation scattering and we find the same expression as obtained by Compton in his fundamental work of 1023.

Cette thèse développe un système d'analyse en ligne compact, précis, rapide et autonome par spectrométrie de fluorescence X raies L, pour quantifier les transuraniens (uranium, plutonium et américium) présents dans les solutions et effluents des procédés du plutonium. Au cours de cette étude, la configuration, les paramètres de ce système et une méthode de quantification non destructive ont été définis puis la capacité du spectromètre à dissocier ces éléments dans de fortes concentrations relatives a été vérifiée. Des solutions contenant des éléments non radioactifs ont d'abord été étudiées afin de s'affranchir des effets dus à la désintégration des transuraniens et d'optimiser efficacement le spectromètre. Par simulations Monte-Carlo avec le code PENELOPE, une méthode de quantification a été mise au point et diverses configurations pour optimiser l'intensité d'excitation de l'échantillon et mesurer une raie de diffusion Compton de la source X ont été testées numériquement. Ces configurations ont été expérimentées avec un spectromètre prototype sur des solutions non radioactives pour valider et compléter la configuration la plus intéressante. Des solutions contenant des éléments en fortes concentrations relatives ont été analysées afin de déterminer une méthode de déconvolution des spectres avec le logiciel COLEGRAM et démontrer la faculté de cette méthode à quantifier de telles solutions. Quelques solutions d'uranium et de plutonium ont été analysées pour s'approcher au plus près des futures conditions expérimentales, caractériser et diminuer les effets dus à la désintégration des radioéléments. / This thesis deals with the development of a new compact, accurate, fast, without cooling liquid, fluorescence L X-ray spectrometer, with the aim to determinate online transuranic elements (uranium, plutonium and americium) in nuclear materials reprocessing. The objective was to define the configuration and the characteristics of this spectrometer and the method to quantify transuranic elements between 0.1 g/L and 20 g/L. To minimize as law as possible the manipulation of these elements, we have used an original approach, namely Monte-Carlo simulations and none radioactive surrogate elements. The study of these solutions allowed to eliminate the specific effects of transuranic elements decay (internal conversion) and to optimize the spectrometer. Monte-Carlo simulations with the PENELOPE code were used for two reasons. Firstly, we have developed an analytical method to correct the matrix effects. Then, we have selected three systems to produce a quasi-monochromatic X-rays beam from the X-ray generator, to optimize the intensity of the L X-ray fluorescence spectra, and to measure the Compton scatter peak. These systems were then tested with an adjustable spectrometer in order to select and optimize the best configuration. We have shown that, after peaks and left tails separation from spectra with COLEGRAM software, the spectrometer can be used to analyze solutions with various concentrations of thallium and bismuth. Several solutions of uranium or plutonium were analyzed to determine the effects of interferences from gamma rays and internal conversion with the fluorescence L X-rays. These effects have been corrected by subtracting a passive spectrum to an active one.

A dissertação pode ser dividida em duas partes: a primeira contém uma adaptação do modelo fenomenológico de Einstein conhecido como \"método dos coeficientes A e B\". As modificações são feitas no contexto da Eletrodinâmica Estocástica, uma teoria na qual as flutuações de ponto zero do campo eletromagnético são consideradas reais e clássicas. Nós obtemos, num estudo não relativístico e clássico, relações entre a energia e momento de partículas livres e a frequência da radiação transferida. Estas relações coincidem com as bem conhecidas relações que representam a conservação do quadrivetor momento-energia em espalhamento fóton-elétron. Na segunda parte nós tentamos descrever, de uma maneira qualitativa, o efeito Compton no espírito da Eletrodinâmica Estocástica. Encontramos indicações de que a ação combinada da força da reação da radiação e das flutuações de ponto zero é capaz de conferir à partícula carregada uma alta velocidade de recuo, e verificamos que a mesma é justamente a necessária para explanar o deslocamento da frequência observado como sendo devido ao efeito Doppler. Também calculamos a seção de choque diferencial para o espalhamento de radiação e encontramos a mesma expressão obtida por Compton no seu trabalho fundamental de 1923. / The dissertation may be divided in two parts: the first one contains an adaptation of Einstein\'s phenomenological model known as \"method of coefficients A and B\". The modifications are done in the framework of Stochastic Electrodynamics, a theory in wich the zero point fluctuations of the electromagnetic field are considered real and classical. We obtain, in a nonrelativistic and Classical approach, relations among the energy and momentum of free particles and the frequency of the exchanged radiation. These relations are coincident with the well known ones who depict the four-momentum conservation in photon-electron scattering. In the second part, we try to describe, in a qualitative manner, the Compton scattering in the spirit of Stochastic Electrodynamics. We find indications that the combined action of the radiation reaction force and the zero point flutuating field are able to give the charged particle a high recoil velocity, and we verify this one is just the necessary to explain the frequency shift as due to a double Doppler shift. We also calculate the differential cross section for the radiation scattering and we find the same expression as obtained by Compton in his fundamental work of 1023.

An increasing number of cancer patients is treated with proton beams or other light ion beams which allow to deliver dose precisely to the tumor. However, the depth dose distribution of these particles, which enables this precision, is sensitive to deviations from the treatment plan, as e.g. anatomical changes. Thus, to assure the quality of the treatment, a non-invasive in-vivo dose verification is highly desired. This monitoring of particle therapy relies on the detection of secondary radiation which is produced by interactions between the beam particles and the nuclei of the patient’s tissue. Up to now, the only clinically applied method for in-vivo dosimetry is Positron Emission Tomography which makes use of the beta+-activity produced during the irradiation (PT-PET). Since from a PT-PET measurement the applied dose cannot be directly deduced, the simulated distribution of beta+-emitting nuclei is used as a basis for the analysis of the measured PT-PET data. Therefore, the reliable modeling of the production rates and the spatial distribution of the beta+-emitters is required. PT-PET applied during instead of after the treatment is referred to as in-beam PET. A challenge concerning in-beam PET is the design of the PET camera, because a standard full-ring scanner is not feasible. For instance, a double-head PET camera is applicable, but low count rates and the limited solid angle coverage can compromise the image quality. For this reason, a detector system which provides a time resolution allowing the incorporation of time-of-flight information (TOF) into the iterative reconstruction algorithm is desired to improve the quality of the reconstructed images. Secondly, Prompt Gamma Imaging (PGI), a technique based on the detection of prompt gamma-rays, is currently pursued. Concerning the emissions of prompt gamma-rays during particle irradiation, experimental data is not sufficiently available, making simulations necessary. Compton cameras are based on the detection of incoherently scattered photons and are investigated with respect to PGI. Monte Carlo simulations serve for the optimization of the camera design and the evaluation of criteria for the selection of measured events. Thus, for in-beam PET and PGI dedicated detection systems and, moreover, profound knowledge about the corresponding radiation fields are required. Using various simulation codes, this thesis contributes to the modelling of the beta+-emitters and photons produced during particle irradiation, as well as to the evaluation and optimization of hardware for both techniques. Concerning the modeling of the production of the relevant beta+-emitters, the abilities of the Monte Carlo simulation code PHITS and of the deterministic, one-dimensional code HIBRAC were assessed. The Monte Carlo tool GEANT4 was applied for an additional comparison. For irradiations with protons, helium, lithium, and carbon, the depth-dependent yields of the simulated beta+-emitters were compared to experimental data. In general, PHITS underestimated the yields of the considered beta+-emitters in contrast to GEANT4 which provided acceptable values. HIBRAC was substantially extended to enable the modeling of the depth-dependent yields of specific nuclides. For proton beams and carbon ion beams HIBRAC can compete with GEANT4 for this application. Since HIBRAC is fast, compact, and easy to modify, it could be a basis for the simulations of the beta+-emitters in clinical application. PHITS was also applied to the modeling of prompt gamma-rays during proton irradiation following an experimental setup. From this study, it can be concluded that PHITS could be an alternative to GEANT4 in this context. Another aim was the optimization of Compton camera prototypes. GEANT4 simulations were carried out with the focus on detection probabilities and the rate of valid events. Based on the results, the feasibility of a Compton camera setup consisting of a CZT detector and an LSO or BGO detector was confirmed. Several recommendations concerning the design and arrangement of the Compton camera prototype were derived. Furthermore, several promising event selection strategies were evaluated. The GEANT4 simulations were validated by comparing simulated to measured energy depositions in the detector layers. This comparison also led to the reconsideration of the efficiency of the prototype. A further study evaluated if electron-positron pairs resulting from pair productions could be detected with the existing prototype in addition to Compton events. Regarding the efficiency and the achievable angular resolution, the successful application of the considered prototype as pair production camera to the monitoring of particle therapy is questionable. Finally, the application of a PET camera consisting of Resistive Plate Chambers (RPCs) providing a good time resolution to in-beam PET was discussed. A scintillator-based PET camera based on a commercially available scanner was used as reference. This evaluation included simulations of the detector response, the image reconstructions using various procedures, and the analysis of image quality. Realistic activity distributions based on real treatment plans for carbon ion therapy were used. The low efficiency of the RPC-based PET camera led to images of poor quality. Neither visually nor with the semi-automatic tool YaPET a reliable detectability of range deviations was possible. The incorporation of TOF into the iterative reconstruction algorithm was especially advantageous for the considered RPC-based PET camera in terms of convergence and artifacts. The application of the real-time capable back projection method Direct TOF for the RPCbased PET camera resulted in an image quality comparable to the one achieved with the iterative algorihms. In total, this study does not indicate the further investigation of RPC-based PET cameras with similar efficiency for in-beam PET application. To sum up, simulation studies were performed aimed at the progress of in-vivo dosimetry. Regarding the modeling of the beta+-emitter production and prompt gamma-ray emissions, different simulation codes were evaluated. HIBRAC could be a basis for clinical PT-PET simulations, however, a detailed validation of the underlying cross section models is required. Several recommendations for the optimization of a Compton Camera prototype resulted from systematic variations of the setup. Nevertheless, the definite evaluation of the feasibility of a Compton camera for PGI can only be performed by further experiments. For PT-PET, the efficiency of the detector system is the crucial factor. Due to the obtained results for the considered RPC-based PET camera, the focus should be kept to scintillator-based PET cameras for this purpose.

Accelerated protons are excellent candidates for treating several types of tumours. Such charged particles stop at a defined depth, where their ionisation density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimises the damage to normal tissue compared to photon therapy. Nonetheless, inherent range uncertainties cast doubts on the irradiation of tumours close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of proton over photon therapy and limits its ultimate aspirations. Prompt gamma rays, a by-product of the irradiation that is correlated to the dose deposition, are reliable signatures for the detection of range deviations and even for three-dimensional in vivo dosimetry. In this work, two methods for Prompt Gamma-ray Imaging (PGI) are investigated: the Compton camera (Cc) and the Prompt Gamma-ray Timing (PGT). Their applicability in a clinical scenario is discussed and compared. The first method aspires to reconstruct the prompt gamma ray emission density map based on an iterative imaging algorithm and multiple position sensitive gamma ray detectors. These are arranged in scatterer and absorber plane. The second method has been recently proposed as an alternative to collimated PGI systems and relies on timing spectroscopy with a single monolithic detector. The detection times of prompt gamma rays encode essential information about the depth-dose profile as a consequence of the measurable transit time of ions through matter. At Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and OncoRay, detector components are characterised in realistic radiation environments as a step towards a clinical Cc. Conventional block detectors deployed in commercial Positron Emission Tomography (PET) scanners, made of Cerium-doped lutetium oxyorthosilicate - Lu2SiO5:Ce (LSO) or Bismuth Germanium Oxide - Bi4Ge3O12 (BGO) scintillators, are suitable candidates for the absorber of a Cc due to their high density and absorption efficiency with respect to the prompt gamma ray energy range (several MeV). LSO and BGO block detectors are compared experimentally in clinically relevant radiation fields in terms of energy, spatial and time resolution. On a different note, two BGO block detectors (from PET scanners), arranged as the BGO block Compton camera (BbCc), are deployed for simple imaging tests with high energy prompt gamma rays produced in homogeneous Plexiglas targets by a proton pencil beam. The rationale is to maximise the detection efficiency in the scatterer plane despite a moderate energy resolution. Target shifts, increase of the target thickness and beam energy variation experiments are conducted. Concerning the PGT concept, in a collaboration among OncoRay, HZDR and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen) with several detectors and heterogeneous phantoms is performed. The sensitivity of the method to range shifts is investigated, the robustness against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterised for different proton energies. With respect to the material choice for the absorber of the Cc, the BGO scintillator closes the gap with respect to the brighter LSO. The reason behind is the high energies of prompt gamma rays compared to the PET scenario, which increase significantly the energy, spatial and time resolution of BGO. Regarding the BbCc, shifts of a point-like radioactive source are correctly detected, line sources are reconstructed, and one centimetre proton range deviations are identified based on the evident changes of the back projection images. Concerning the PGT experiments, for clinically relevant doses, range differences of five millimetres in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to two millimetres are detectable. Experimental data are well reproduced by analytical modelling. The Cc and the PGT are ambitious approaches for range verification in proton therapy based on PGI. Intensive detector characterisation and tests in clinical facilities are mandatory for developing robust prototypes, since the energy range of prompt gamma rays spans over the MeV region, not used traditionally in medical applications. Regarding the material choice for the Cc: notwithstanding the overall superiority of LSO, BGO catches up in the field of PGI. It can be considered as a competitive alternative to LSO for the absorber plane due to its lower price, higher photoabsorption efficiency, and the lack of intrinsic radioactivity. The results concerning the BbCc, obtained with relatively simple means, highlight the potential application of Compton cameras for high energy prompt gamma ray imaging. Nevertheless, technical constraints like the low statistics collected per pencil beam spot (if clinical currents are used) question their applicability as a real-time and in vivo range verification method in proton therapy. The PGT is an alternative approach, which may have faster translation into clinical practice due to its lower price and higher efficiency. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype, that may detect significant range deviations for the strongest beam spots. The experimental results emphasise the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry. / Beschleunigte Protonen sind ausgezeichnete Kandidaten für die Behandlung von diversen Tumorarten. Diese geladenen Teilchen stoppen in einer bestimmten Tiefe, bei der die Ionisierungsdichte maximal ist. Da die deponierte Dosis hinter der distalen Kante sehr klein ist, minimiert die Protonentherapie den Schaden an normalem Gewebe verglichen mit der Photonentherapie. Inhärente Reichweitenunsicherheiten stellen jedoch die Bestrahlung von Tumoren in der Nähe von Risikoorganen in Frage und führen zur Anwendung von konservativen Sicherheitssäumen. Dadurch werden die potentiellen Vorteile der Protonen- gegenüber der Photonentherapie sowie ihre letzten Ziele eingeschränkt. Prompte Gammastrahlung, ein Nebenprodukt der Bestrahlung, welche mit der Dosisdeposition korreliert, ist eine zuverlässige Signatur um Reichweitenunterschiede zu detektieren und könnte sogar für eine dreidimensionale in vivo Dosimetrie genutzt werden. In dieser Arbeit werden zwei Methoden für Prompt Gamma-ray Imaging (PGI) erforscht: die Compton-Kamera (CK) und das Prompt Gamma-ray Timing (PGT)-Konzept. Des Weiteren soll deren Anwendbarkeit im klinischen Szenario diskutiert und verglichen werden. Die erste Methode strebt nach der Rekonstruktion der Emissionsdichtenverteilung der prompten Gammastrahlung und basiert auf einem iterativen Bildgebungsalgorithmus sowie auf mehreren positionsempfindlichen Detektoren. Diese werden in eine Streuer- und Absorberebene eingeteilt. Die zweite Methode ist vor Kurzem als eine Alternative zu kollimierten PGI Systemen vorgeschlagen worden, und beruht auf dem Prinzip der Zeitspektroskopie mit einem einzelnen monolithischen Detektor. Die Detektionszeiten der prompten Gammastrahlen beinhalten entscheidende Informationen über das Tiefendosisprofil aufgrund der messbaren Durchgangszeit von Ionen durch Materie. Am Helmholtz-Zentrum Dresden-Rossendorf (HZDR) und OncoRay werden Detektorkomponenten in realistischen Strahlungsumgebungen als ein Schritt zur klinischen CK charakterisiert. Konventionelle Blockdetektoren, welche in kommerziellen Positronen-Emissions-Tomographie (PET)-Scannern zum Einsatz kommen und auf Cer dotiertem Lutetiumoxyorthosilikat - Lu2SiO5:Ce (LSO) oder Bismutgermanat - Bi4Ge3O12 (BGO) Szintillatoren basieren, sind geeignete Kandidaten für den Absorber einer CK wegen der hohen Dichte und Absorptionseffizienz im Energiebereich von prompten Gammastrahlen (mehrere MeV). LSO- und BGO-Blockdetektoren werden in klinisch relevanten Strahlungsfeldern in Bezug auf Energie-, Orts- und Zeitauflösung verglichen. Weiterhin werden zwei BGO-Blockdetektoren (von PET-Scannern), angeordnet als BGO Block Compton-Kamera (BBCK), benutzt, um die Bildgebung von hochenergetischen prompten Gammastrahlen zu untersuchen, die in homogenen Plexiglas-Targets durch einen Protonen-Bleistiftstrahl emittiert werden. Die Motivation hierfür ist, die Detektionseffizienz der Streuerebene zu maximieren, wobei jedoch die Energieauflösung vernachlässigt wird. Targetverschiebungen, sowie Änderungen der Targetdicke und der Teilchenenergie werden untersucht. In einer Kollaboration zwischen OncoRay, HZDR and IBA, wird der erste Test des PGT-Konzepts an einem klinischen Protonenbeschleuniger (Westdeutsches Protonentherapiezentrum Essen) mit mehreren Detektoren und heterogenen Phantomen durchgeführt. Die Sensitivität der Methode hinsichtlich Reichweitenveränderungen wird erforscht. Des Weiteren wird der Einfluss von Untergrund und Stabilität des Zeitprofils des Strahlenbündels untersucht, sowie die Zeitverschmierung des Bündels für verschiedene Protonenenergien charakterisiert. Für die Materialauswahl für den Absorber der CK ergibt sich, dass sich BGO dem lichtstärkeren LSO Szintillator angleicht. Der Grund dafür sind die höheren Energien der prompten Gammastrahlung im Vergleich zum PET Szenario, welche die Energie-, Orts- und Zeitauflösung von BGO stark verbessern. Anhand von offensichtlichen Änderungen der Rückprojektionsbilder zeigt sich, dass mit der BBCK Verschiebungen einer punktförmigen radioaktiven Quelle erfolgreich detektiert, Linienquellen rekonstruiert und Verschiebungen der Protonenreichweite um einen Zentimeter identifiziert werden. Für die PGT-Experimente können mit einem einzigen Detektor Reichweitenunterschiede von fünf Millimetern für definierte heterogene Targets bei klinisch relevanten Dosen detektiert werden. Dies wird durch den numerischen Vergleich der Spektrumform ermöglicht. Bei größerer Ereigniszahl können Reichweitenunterschiede von bis zu zwei Millimetern detektiert werden. Die experimentellen Daten werden durch analytische Modellierung wiedergegeben. Die CK und das PGT-Konzept sind ambitionierte Ansätze zur Verifizierung der Reichweite in der Protonentherapie basierend auf PGI. Intensive Detektorcharakterisierung und Tests an klinischen Einrichtungen sind Pflicht für die Entwicklung geeigneter Prototypen, da der Energiebereich prompter Gammastrahlung sich über mehrere MeV erstreckt, was nicht dem Normbereich der traditionellen medizinischen Anwendungen entspricht. Im Bezug auf die Materialauswahl der CK wird ersichtlich, dass BGO trotz der allgemeinen Überlegenheit von LSO für die Anwendung im Bereich PGI aufholt. Wegen des niedrigeren Preises, der höheren Photoabsorptionseffizienz und der nicht vorhandenen Eigenaktivität erscheint BGO als eine konkurrenzfähige Alternative für die Absorberebene der CK im Vergleich zu LSO. Die Ergebnisse der BBCK, welche mit relativ einfachen Mitteln gewonnen werden, heben die potentielle Anwendung von Compton-Kameras für die Bildgebung prompter hochenergetischer Gammastrahlen hervor. Trotzdem stellen technische Beschränkungen wie die mangelnde Anzahl von Messereignissen pro Bestrahlungspunkt (falls klinische Ströme genutzt werden) die Anwendbarkeit der CK als Echtzeit- und in vivo Reichweitenverifikationsmethode in der Protonentherapie in Frage. Die PGT-Methode ist ein alternativer Ansatz, welcher aufgrund der geringeren Kosten und der höheren Effizienz eine schnellere Umsetzung in die klinische Praxis haben könnte. Ein Protonenbunchmonitor, höherer Detektordurchsatz und eine quantitative Reichweitenrekonstruktion sind die weiteren Schritte in Richtung eines klinisch anwendbaren Prototyps, der signifikante Reichweitenunterschiede für die stärksten Bestrahlungspunkte detektieren könnte. Die experimentellen Ergebnisse unterstreichen das Potential dieser Reichweitenverifikationsmethode an einem klinischen Bleistiftstrahl und lassen diesen neuartigen Ansatz als eine vielversprechende Alternative auf dem Gebiet der in vivo Dosimetrie erscheinen.

Background The finite range of a proton beam in tissue and the corresponding steep distal dose gradient near the end of the particle track open new vistas for the delivery of a highly target-conformal dose distribution in radiation therapy. Compared to a classical photon treatment, the potential therapeutic benefit of a particle treatment is a significant dose reduction in the tumor-surrounding tissue at a comparable dose level applied to the tumor. Motivation The actually applied particle range, and therefor the dose deposition in the target volume, is quite sensitive to the tissue composition in the path of the protons. Particle treatments are planned via computed tomography images, acquired prior to the treatment. The conversion from photon stopping power to proton stopping power induces an important source of range-uncertainty. Furthermore, anatomical deviations from planning situation affect the accurate dose deposition. Since there is no clinical routine measurement of the actually applied particle range, treatments are currently planned to be robust in favor of optimal regarding the dose delivery. Robust planning incorporates the application of safety margins around the tumor volume as well as the usage of (potentially) unfavorable field directions. These pretreatment safety procedures aim to secure dose conformality in the tumor volume, however at the price of additional dose to the surrounding tissue. As a result, the unverified particle range constraints the principle benefit of proton therapy. An on-line, in-vivo range-verification would therefore bring the potential of particle therapy much closer to the daily clinical routine. Materials and methods This work contributes to the field of in-vivo treatment verification by the methodical investigation of range assessment via the detection of prompt gamma-rays, a side product emitted due to proton-tissue interaction. In the first part, the concept of measuring the spatial prompt gamma-ray emission profile with a Compton camera is investigated with a prototype system consisting of a CdZnTe cross strip detector as scatter plane and three side-by-side arranged, segmented BGO block detectors as absorber planes. In the second part, the novel method of prompt gamma-ray timing (PGT) is introduced. This technique has been developed in the scope of this work and a patent has been applied for. The necessary physical considerations for PGT are outlined and the feasibility of the method is supported with first proof-of-principle experiments. Results Compton camera: Utilizing a 22-Na source, the feasibility of reconstructing the emission scene of a point source at 1.275 MeV was verified. Suitable filters on the scatter-absorber coincident timing and the respective sum energy were defined and applied to the data. The source position and corresponding source displacements could be verified in the reconstructed Compton images. In a next step, a Compton imaging test at 4.44 MeV photon energy was performed. A suitable test setup was identified at the Tandetron accelerator at the Helmholtz-Zentrum Dresden-Rossendorf, Germany. This measurement setup provided a monoenergetic, point-like source of 4.44 MeV gamma-rays, that was nearly free of background. Here, the absolute gamma-ray yield was determined. The Compton imaging prototype was tested at the Tandetron regarding (i) the energy resolution, timing resolution, and spatial resolution of the individual detectors, (ii) the imaging capabilities of the prototype at 4.44 MeV gamma-ray energy and (iii) the Compton imaging efficiency. In a Compton imaging test, the source position and the corresponding source displacements were verified in the reconstructed Compton images. Furthermore, via the quantitative gamma-ray emission yield, the Compton imaging efficiency at 4.44 MeV photon energy was determined experimentally. PGT: The concept of PGT was developed and introduced to the scientific community in the scope of this thesis. A theoretical model for PGT was developed and outlined. Based on the theoretical considerations, a Monte Carlo (MC) algorithm, capable of simulating PGT distributions was implemented. At the KVI-CART proton beam line in Groningen, The Netherlands, time-resolved prompt gamma-ray spectra were recorded with a small scale, scintillator based detection system. The recorded data were analyzed in the scope of PGT and compared to the measured data, yielding in an excellent agreement and thus verifying the developed theoretical basis. For a hypothetical PGT imaging setup at a therapeutic proton beam it was shown, that the statistical error on the range determination could be reduced to 5 mm at a 90 % confidence level for a single spot of 5x10E8 protons. Conclusion Compton imaging and PGT were investigated as candidates for treatment verification, based on the detection of prompt gamma-rays. The feasibility of Compton imaging at photon energies of several MeV was proven, which supports the approach of imaging high energetic prompt $gamma$-rays. However, the applicability of a Compton camera under therapeutic conditions was found to be questionable, due to (i) the low device detection efficiency and the corresponding limited number of valid events, that can be recorded within a single treatment and utilized for image reconstruction, and (ii) the complexity of the detector setup and attached readout electronics, which make the development of a clinical prototype expensive and time consuming. PGT is based on a simple time-spectroscopic measurement approach. The collimation-less detection principle implies a high detection efficiency compared to the Compton camera. The promising results on the applicability under treatment conditions and the simplicity of the detector setup qualify PGT as method well suited for a fast translation towards a clinical trial. / Hintergrund Strahlentherapie ist eine wichtige Modalität der therapeutischen Behandlung von Krebs. Das Ziel dieser Behandlungsform ist die Applikation einer bestimmten Strahlendosis im Tumorvolumen, wobei umliegendes, gesundes Gewebe nach Möglichkeit geschont werden soll. Bei der Bestrahlung mit einem hochenergetischen Protonenstrahl erlaubt die wohldefinierte Reichweite der Teilchen im Gewebe, in Kombination mit dem steilen, distalen Dosisgradienten, eine hohe Tumor-Konformalität der deponierten Dosis. Verglichen mit der klassisch eingesetzten Behandlung mit Photonen ergibt sich für eine optimiert geplante Behandlung mit Protonen ein deutlich reduziertes Dosisnivau im den Tumor umgebenden Gewebe. Motivation Die tatsächlich applizierte Reichweite der Protonen im Körper, und somit auch die lokal deponierte Dosis, ist stark abhängig vom Bremsvermögen der Materie im Strahlengang der Protonen. Bestrahlungspläne werden mit Hilfe eines Computertomographen (CT) erstellt, wobei die CT Bilder vor der eigentlichen Behandlung aufgenommen werden. Ein CT misst allerdings lediglich den linearen Schwächungskoeffizienten für Photonen in der Einheit Hounsfield Units (HU). Die Ungenauigkeit in der Umrechnung von HU in Protonen-Bremsvermögen ist, unter anderem, eine wesentliche Ursache für die Unsicherheit über die tatsächliche Reichweite der Protonen im Körper des Patienten. Derzeit existiert keine routinemäßige Methode, um die applizierte Dosis oder auch die Protonenreichweite in-vivo und in Echtzeit zu bestimmen. Um das geplante Dosisniveau im Tumorvolumen trotz möglicher Reichweiteunterschiede zu gewährleisten, werden die Bestrahlungspläne für Protonen auf Robustheit optimiert, was zum Einen das geplante Dosisniveau im Tumorvolumen trotz auftretender Reichweiteveränderungen sicherstellen soll, zum Anderen aber auf Kosten der möglichen Dosiseinsparung im gesunden Gewebe geht. Zusammengefasst kann der Hauptvorteil einer Therapie mit Protonen wegen der Unsicherheit über die tatsächlich applizierte Reichweite nicht wirklich realisiert. Eine Methode zur Bestimmung der Reichweite in-vivo und in Echtzeit wäre daher von großem Nutzen, um das theoretische Potential der Protonentherapie auch in der praktisch ausschöpfen zu können. Material und Methoden In dieser Arbeit werden zwei Konzepte zur Messung prompter Gamma-Strahlung behandelt, welche potentiell zur Bestimmung der Reichweite der Protonen im Körper eingesetzt werden können. Prompte Gamma-Strahlung entsteht durch Proton-Atomkern-Kollision auf einer Zeitskala unterhalb von Picosekunden entlang des Strahlweges der Protonen im Gewebe. Aufgrund der prompten Emission ist diese Form der Sekundärstrahlung ein aussichtsreicher Kandidat für eine Bestrahlungs-Verifikation in Echtzeit. Zum Einen wird die Anwendbarkeit von Compton-Kameras anhand eines Prototyps untersucht. Dabei zielt die Messung auf die Rekonstruktion des örtlichen Emissionsprofils der prompten Gammas ab. Zum Zweiten wird eine, im Rahmen dieser Arbeit neu entwickelte Messmethode, das Prompt Gamma-Ray Timing (PGT), vorgestellt und international zum Patent angemeldet. Im Gegensatz zu bereits bekannten Ansätzen, verwendet PGT die endliche Flugzeit der Protonen durch das Gewebe und bestimmt zeitliche Emissionsprofile der prompten Gammas. Ergebnisse Compton Kamera: Die örtliche Emissionsverteilung einer punktförmigen 22-Na Quelle wurde wurde bei einer Photonenenergie von 1.275 MeV nachgewiesen. Dabei konnten sowohl die absolute Quellposition als auch laterale Verschiebungen der Quelle rekonstruiert werden. Da prompte Gamma-Strahlung Emissionsenergien von einigen MeV aufweist, wurde als nächster Schritt ein Bildrekonstruktionstest bei 4.44 MeV durchgeführt. Ein geeignetes Testsetup wurde am Tandetron Beschleuniger am Helmholtz-Zentrum Dresden-Rossendorf, Deutschland, identifiziert, wo eine monoenergetische, punktförmige Emissionverteilung von 4.44 MeV Photonen erzeugt werden konnte. Für die Detektoren des Prototyps wurden zum Einen die örtliche und zeitliche Auflösung sowie die Energieauflösungen untersucht. Zum Anderen wurde die Emissionsverteilung der erzeugten 4.44 MeV Quelle rekonstruiert und die zugehörige Effizienz des Prototyps experimentell bestimmt. PGT: Für das neu vorgeschlagene Messverfahren PGT wurden im Rahmen dieser Arbeit die theoretischen Grundlagen ausgearbeitet und dargestellt. Darauf basierend, wurde ein Monte Carlo (MC) Code entwickelt, welcher die Modellierung von PGT Spektren ermöglicht. Am Protonenstrahl des Kernfysisch Verschneller Institut (KVI), Groningen, Niederlande, wurden zeitaufgelöste Spektren prompter Gammastrahlung aufgenommen und analysiert. Durch einen Vergleich von experimentellen und modellierten Daten konnte die Gültigkeit der vorgelegten theoretischen Überlegungen quantitativ bestätigt werden. Anhand eines hypothetischen Bestrahlungsszenarios wurde gezeigt, dass der statistische Fehler in der Bestimmung der Reichweite mit einer Genauigkeit von 5 mm bei einem Konfidenzniveau von 90 % für einen einzelnen starken Spot 5x10E8 Protonen mit PGT erreichbar ist. Schlussfolgerungen Für den Compton Kamera Prototyp wurde gezeigt, dass eine Bildgebung für Gamma-Energien einiger MeV, wie sie bei prompter Gammastrahlung auftreten, möglich ist. Allerdings erlaubt die prinzipielle Abbildbarkeit noch keine Nutzbarkeit unter therapeutischen Strahlbedingungen nicht. Der wesentliche und in dieser Arbeit nachgewiesene Hinderungsgrund liegt in der niedrigen (gemessenen) Nachweiseffizienz, welche die Anzahl der validen Daten, die für die Bildrekonstruktion genutzt werden können, drastisch einschränkt. PGT basiert, im Gegensatz zur Compton Kamera, auf einem einfachen zeit-spektroskopischen Messaufbau. Die kollimatorfreie Messmethode erlaubt eine gute Nachweiseffizienz und kann somit den statistischen Fehler bei der Reichweitenbestimmung auf ein klinisch relevantes Niveau reduzieren. Die guten Ergebnissen und die ausgeführten Abschätzungen für therapeutische Bedingungen lassen erwarten, dass PGT als Grundlage für eine Bestrahlungsverifiktation in-vivo und in Echtzeit zügig klinisch umgesetzt werden kann.

Les sursauts gamma (GRBs pour "Gamma-Ray Bursts" en anglais) sont de brèves bouffées très énergétiques de rayonnement de haute énergie qui sont émises sur de courtes échelles de temps (fraction de seconde à plusieurs minutes). L'émission intense des sursauts gamma à haute énergie est supposée provenir d'un trou noir de masse stellaire nouvellement formé, accompagné d'un vent collimaté (i.e. un jet) se propageant à vitesse relativiste. L'émission est observée suivant deux phases successives, la phase prompte très erratique, et la phase de rémanence, moins lumineuse. Les deux instruments embarqués sur le satellite Fermi, le "Gamma-ray Burst Monitor" (GBM) et le "Large Area Telescope" (LAT), permettent d'étudier l'émission prompte des sursauts gamma sur une grande plage d'énergie (de ~10 keV à ~100 GeV). L'objectif principal de ma thèse est l'analyse et l'interprétation des propriétés spectrales et temporelles de l'émission prompte des GRBs observés par Fermi, en particulier avec les nouvelles données du LAT (Pass 8) qui ont été rendues publiques en juin 2015.La première partie de mon travail est une analyse spectrale résolue en temps de la phase prompte du sursaut GRB 090926A avec les données du GBM et du LAT. Mes résultats confirment avec un meilleur niveau de confiance la présence d'une cassure spectrale à ~400 MeV, qui est observée en coincidence avec un pic d'émission très court. Ils révèlent que cette atténuation spectrale est présente durant toute l'émission prompte du sursaut, et que l'énergie de cassure augmente jusqu'au GeV. L'interprétation de la cassure spectrale en termes d'absorption gamma ou de courbure naturelle du spectre d'émission Compton inverse (CI) dans le régime Klein-Nishina fournit des contraintes fortes sur le facteur de Lorentz du jet. Mes résultats conduisent en outre à des rayons d'émission R ∼10^14 cm qui sont compatibles avec une origine interne de l'émission du keV au GeV au-dessus de la photosphère du jet.La seconde partie de mon travail est une exploration du modèle de chocs internes développé par des collaborateurs à l'Institut d'Astrophysique de Paris (IAP). Ce modèle simule la dynamique du jet et les processus d'émission (synchrotron et CI) d'une population d'électrons accélérés aux chocs. J'ai simulé la réponse instrumentale de Fermi à un sursaut synthétique fourni par ce code numérique, et j'ai construit une fonction paramétrique qui peut être utilisée pour ajuster le modèle aux spectres de sursauts du keV au MeV. J'ai appliqué cette fonction avec succès à un échantillon de 64 sursauts brillants détectés par le GBM. J'ai aussi confronté le modèle de l'IAP au spectre d'émission prompte de GRB 090926A. Mes résultats montrent un bon accord, et j'ai identifié quelques pistes pour les améliorer. Les spectres synthétiques sont plus larges que tous les spectres dans l'échantillon du GBM. En conséquence, je discute brièvement quelques pistes de développements théoriques qui pourraient améliorer l'accord du modèle avec les observations, ainsi que des avancées observationnelles attendues dans le futur. / Gamma-Ray Bursts (GRBs) are very energetic and brief flashes of high-energy radiations which are emitted in a short time scale (fraction of a second to several minutes). The GRB bright emission is thought to be powered by a newly formed stellar-mass black hole that is accompanied by a collimated outflow (i.e. a jet) moving at a relativistic speed. The emission is observed as two successive phases: the highly variable “prompt” phase and the late and less luminous “afterglow” phase. The two instruments on board the Fermi space telescope, the Gamma-ray Burst Monitor (GBM) and the Large Area Telescope (LAT), allow the study of GRB prompt emission over a broad energy range (from ~10 keV to ~100 GeV). In June 2015, a new set of LAT data (Pass 8) was publicly released, which were generated using improved algorithms of reconstruction and classification of gamma-ray events. The main goal of my thesis is the analysis and interpretation of the spectral and temporal properties of the prompt emission phase of the GRBs observed by Fermi, especially using LAT Pass8 data.In the first part of my work, I performed a detailed time-resolved spectral analysis of the prompt phase of GRB 090926A with GBM and LAT data. My results confirm with a greater significance the spectral break at ∼400 MeV that is observed during a fast variability pulse, and they also reveal the presence of a spectral attenuation throughout the GRB prompt emission, as well as an increase of the break energy up to the GeV domain. I interpreted the spectral break in terms of gamma-ray absorption or as a natural curvature of the inverse Compton (IC) emission in the Klein-Nishina regime. Strong constraints on the jet Lorentz factor were obtained in both scenarios. My results lead also to emission radii R ∼10^14 cm, which are consistent with an internal origin of both the keV-MeV and GeV prompt emissions above the jet photosphere.The second part of my work is an exploration of the internal shock model that has been developed by collaborators at the "Institut d'Astrophysique de Paris" (IAP). This model simulates the GRB jet dynamics and the radiations (synchrotron and IC processes) from a population of shock-accelerated electrons. I simulated the response of the Fermi instruments to the synthetic GRB spectra provided by this numerical code. From these simulations, I built a new parametric function that can be used to fit the keV-MeV spectra of GRBs with the model. I applied successfully this function to a sample of 64 GBM bright GRBs. I confronted also the IAP model to the prompt emission spectrum of GRB 090926A. I obtained a relatively good agreement and I identified a couple of solutions that may improve it. The synthetic spectra are wider than any GRB spectra in the GBM sample. I present some theoretical developments that could improve the data-model agreement in the future, and I discuss possible advances from future GRB missions as well.