The 12C+16O breakup of 28Si and the 12C+12C breakup of 24Mg have been studied following the interaction of a 170 MeV 24Mg beam with 7Li, 9Be,12C and 16O target nuclei. The measurements were performed at the Australian National University in Canberra, using the technique of Resonant Particle Spectroscopy. The breakup fragments from the decay of the resonant nuclei were detected in two Gas-Si-CsI telescopes positioned on opposite sides of the beam axis. The data suggest that the same states in 28Si are populated via the 7Li(24Mg, 12C 16O)3H, 9Be(24Mg,12C 16O)5He and 12c(24Mg,12C 16O)8Be reactions. This implies that the cluster decaying states are populated by direct a-transfer. Breakup has been observed from states in 28Si at excitation energies (spins) of (26.15), 28.17 (13-, 29.51, 29.95, 30.45, 30.76, (31.3), 31.65, 31.90, 32.51, 33.14, 33.41, 33.77, 34.45 (12+,14+) and 35.13 MeV. A consistent theoretical interpretation of the 28Si molecular structures has been given, taking into account the predictions of Nilsson-Strutinsky, a-cluster model and two centre shell model calculations. The present results for the 12C(24Mg,12C 12C)12C reaction agree with previous measurements. In addition, new spin assignments have been proposed for several of the breakup states in 24Mg. States have been observed at excitation energies (spins) of 20.54 (2+), 21.07 (4+), 21.88 (4+), 22.33 (4+), 22.90 (6+), 23.80 (6+,(8+)), 24.56 (8+), 25.14 (6+), 25.72, 26.41 (8+) and 27.12 MeV. Evidence for the population of many of these states via the 16O(24Mg,12C 12C)16O reaction has also been observed. However, the data gave no evidence for either the 7Li(24Mg,12C 12C)7Li or 9Be(24Mg,12C 12C)9Be reactions. The presently available information did not allow an unambiguous determination of the reaction mechanism responsible for the population of the 24Mg breakup states. The performance of the Gas-Si-Csl telescopes has been investigated. For multiplicity 2 events in the silicon strip detectors, a crosstalk has been observed between the two active strips. The energy calibration of the silicon strip detectors for penetrating particles has also been found to differ to that for stopped particles. Empirical corrections for both of these effects have been deduced allowing the simultaneous detection and identification of heavy and light ions within a single telescope. These techniques have been extended to the detection of 8Be → alpha+alpha events over a wide range of alpha-particle energies.

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-06-22T14:26:41Z No. of bitstreams: 0 / Made available in DSpace on 2016-06-22T14:26:41Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-06-22T14:26:41Z No. of bitstreams: 0 / Made available in DSpace on 2016-06-22T14:26:41Z (GMT). No. of bitstreams: 0 / O 99mTc é o radionuclídeo mais utilizado em medicina nuclear. No Brasil os geradores de 99Mo/99mTc são produzidos exclusivamente pelo Centro de Radiofarmácia do IPEN-CNEN/SP, com 99Mo importado de diferentes fornecedores. O 99Mo (t1/2 = 66 h), por ser um produto de fissão do 235U, pode conter impurezas radionuclídicas prejudiciais à saúde humana. Dessa forma, para que o gerador seja utilizado de forma segura, é necessário que o 99Mo seja avaliado por ensaios de controle de qualidade e atenda à alguma especificação descrita em farmacopeia. A Farmacopeia Europeia (FE) apresenta monografia, com parâmetros (identificação, pureza radioquímica e pureza radionuclídica), métodos de análise, e limites, para avaliação da qualidade da solução de [99Mo] na forma de molibdato de sódio, que é utilizada como matéria-prima no preparo dos geradores de 99Mo/99mTc. No entanto, observa-se uma dificuldade na implementação e execução dos métodos por parte dos produtores de geradores, com pouca literatura sobre o assunto, provavelmente devido à falta de praticidade dos métodos propostos e à extensa lista de reagentes utilizados. Nesse trabalho foram avaliados vários parâmetros de qualidade do 99Mo descritos na monografia da FE. Foram estudados métodos de separação do 99Mo de suas impurezas radionuclídicas por extração em fase sólida (SPE) e por TLC. Após separação por SPE, foi proposta a quantificação de metais por ICP-OES para avaliar a porcentagem de retenção de Mo e a porcentagem de recuperação de Ru e Te e Sr em diversos tipos de cartuchos, em substituição ao uso de radiotraçadores. Observou-se que a marca de cartucho de SPE para separação do 99Mo recomendada pela FE apresentou baixa recuperação para Ru, quando comparado aos outros cartuchos de troca aniônica disponíveis no mercado. Amostras de 99Mo de diferentes fornecedores mundiais foram analisadas. Observou-se que é possível realizar a quantificação de 103Ru em amostras de 99Mo mesmo com tempos de decaimento acima de 4 semanas. Um método alternativo de separação do 99Mo do 131I por TLC apresentou resultados promissores. Não foi feita a quantificação das impurezas radionuclídicas emissoras beta e alfa. Todas as amostras analisadas apresentaram resultados dentro das especificações da FE para pureza radioquímica (>95%) e pureza radionuclídica. / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Submitted by Pedro Silva Filho (pfsilva@ipen.br) on 2017-11-21T11:20:13Z No. of bitstreams: 0 / Made available in DSpace on 2017-11-21T11:20:13Z (GMT). No. of bitstreams: 0 / A calibração, por definição, é o processo pelo qual se estabelece uma relação entre valores de medição de um padrão, com as suas respectivas incertezas, e as indicações com as incertezas associadas do instrumento de medição a ser calibrado. Um protocolo de calibração descreve a metodologia a ser aplicada em um processo de calibração. O método escolhido para a obtenção deste protocolo foi o da espectrometria de feixe de raios X associada à simulação pelo método de Monte Carlo, fundamentado no fato de que ambos são considerados métodos absolutos na determinação de parâmetros de feixes de radiação. Neste trabalho foi utilizado o método de Monte Carlo utilizado para obter a função resposta do detector utilizada para a correção dos espectros obtidos do feixe primário de radiação X; deste modo foram calculadas as taxas de kerma destes feixes e comparadas aos valores obtidos com as câmaras de ionização padrão secundário do Laboratório de Calibração de Instrumentos do IPEN (LCI/IPEN). Foram obtidos os coeficientes de calibração para o sistema padrão com diferenças em relação ao fornecido pelo laboratório primário entre 1,3% e 15,3%. Os resultados obtidos indicaram a viabilidade do estabelecimento deste protocolo de calibração utilizando a espectrometria como padrão de referência, com incertezas relativas de 0,62% para k=1. As incertezas associadas ao método proposto foram satisfatórias, para um laboratório padrão secundário e comparáveis a um laboratório primário. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

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.:1. Particle therapy 1.1 Introduction 1.2 The problem of particle range uncertainty 1.3 Currently investigated methods for treatment verification 1.4 Methods for prompt gamma-ray based treatment verification 1.4.1 Prompt gamma-ray imaging (PGI) 1.4.2 Prompt gamma-ray timing (PGT) 2. Physical relations 2.1 Interactions of protons with matter 2.1.1 Stopping of protons 2.1.2 Multiple Coulomb scattering (MCS) 2.1.3 Nonelastic collisions 2.2 Definition of deposited dose and proton range 2.2.1 Definition of dose D 2.2.2 The dose depth Dx , the proton fluence Φ, and the Bragg peak 2.2.3 The particle range 2.3 Production and delivery of proton beams 2.3.1 Acceleration of protons in a isochronous cyclotron 2.3.2 Beam delivery 2.4 Prompt gamma-ray emission 2.4.1 The production of prompt gamma-rays via nonelastic nuclear interactions 2.5 Interactions of photons with matter 2.5.1 Photoelectric absorption 2.5.2 Compton scattering 2.5.3 Pair production 2.5.4 Mass attenuation coefficient μ/ρ 2.6 Detection of photons 2.6.1 Semiconductor detectors 2.6.2 Scintillation detectors 3 Tests of a Compton camera for PGI 3.1 Principle of operation 3.2 Status of preceding work 3.3 Modifications to the existing Compton imaging prototype 3.4 Detectors of the prototype 3.4.1 The CZT scatter plane 3.4.2 The BGO absorber plane 3.4.3 The Compton imaging prototype 3.5 Electronic readout and event generation 3.6 Detector calibration 3.6.1 Calibration of the CZT detector 3.6.2 Calibration of a BGO detector 3.7 Compton imaging at 1.275 MeV photon energy 3.7.1 Imaging setup 3.7.2 Coincident timing 3.7.3 Coincident energy deposition 3.7.4 Image reconstruction 3.8 Compton imaging at 4.44 MeV photon energy 3.8.1 Beam setup at the Tandetron accelerator 3.8.2 Beam tuning at the Tandetron accelerator 3.8.3 The gamma-ray emission yield 3.8.4 Measurement setup 3.8.5 Energy detection 3.8.6 Spatial detection 3.8.7 Coincident timing 3.8.8 Coincident energy deposition 3.8.9 Detection efficiency η 3.8.10 Imaging setup 3.8.11 Image reconstruction 3.9 Implications for a therapeutic Compton imaging scenario 3.10 Summary and discussion 4 Prompt gamma-ray timing (PGT) 4.1 Theoretical description of PGT 4.1.1 Timing of prompt gamma-ray emission 4.1.2 Kinematics of protons 4.1.3 The correlation between spatial and temporal prompt gamma-ray emission in a thick target 4.1.4 Setup for time-resolved measurements of prompt gamma-rays 4.1.5 Uncertainty of the reference time 4.1.6 Standard error of the mean and confidence intervals of statistical momenta 4.1.7 A simplified MC method for the modeling of PGT 4.2 Experimental results 4.2.1 The GAGG detector 4.2.2 Detector energy resolution 4.2.3 Detector time resolution with 60-Co 4.2.4 Energy-resolved detector time resolution - the ELBE experiment 4.2.5 The KVI-CART proton beam line 4.2.6 Time-resolved measurement of prompt gamma-rays 4.2.7 Experimental determination of the system time resolution σ 4.2.8 PGT in dependence of proton transit time 4.3 Towards treatment verification with PGT 4.3.1 MC based PGT in dependence of proton range 4.3.2 MC based PGT at inhomogeneous targets 4.4 Implications for a therapeutic PGT scenario 4.4.1 Range verification for an exemplary PGT setup 4.4.2 Practical restrictions for the therapeutic PGT scenario 4.4.3 Principal limitations of the PGT method 4.5 Summary and outlook 5 Discussion Summary Zusammenfassung Bibliography Acknowledgement / 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.:1. Particle therapy 1.1 Introduction 1.2 The problem of particle range uncertainty 1.3 Currently investigated methods for treatment verification 1.4 Methods for prompt gamma-ray based treatment verification 1.4.1 Prompt gamma-ray imaging (PGI) 1.4.2 Prompt gamma-ray timing (PGT) 2. Physical relations 2.1 Interactions of protons with matter 2.1.1 Stopping of protons 2.1.2 Multiple Coulomb scattering (MCS) 2.1.3 Nonelastic collisions 2.2 Definition of deposited dose and proton range 2.2.1 Definition of dose D 2.2.2 The dose depth Dx , the proton fluence Φ, and the Bragg peak 2.2.3 The particle range 2.3 Production and delivery of proton beams 2.3.1 Acceleration of protons in a isochronous cyclotron 2.3.2 Beam delivery 2.4 Prompt gamma-ray emission 2.4.1 The production of prompt gamma-rays via nonelastic nuclear interactions 2.5 Interactions of photons with matter 2.5.1 Photoelectric absorption 2.5.2 Compton scattering 2.5.3 Pair production 2.5.4 Mass attenuation coefficient μ/ρ 2.6 Detection of photons 2.6.1 Semiconductor detectors 2.6.2 Scintillation detectors 3 Tests of a Compton camera for PGI 3.1 Principle of operation 3.2 Status of preceding work 3.3 Modifications to the existing Compton imaging prototype 3.4 Detectors of the prototype 3.4.1 The CZT scatter plane 3.4.2 The BGO absorber plane 3.4.3 The Compton imaging prototype 3.5 Electronic readout and event generation 3.6 Detector calibration 3.6.1 Calibration of the CZT detector 3.6.2 Calibration of a BGO detector 3.7 Compton imaging at 1.275 MeV photon energy 3.7.1 Imaging setup 3.7.2 Coincident timing 3.7.3 Coincident energy deposition 3.7.4 Image reconstruction 3.8 Compton imaging at 4.44 MeV photon energy 3.8.1 Beam setup at the Tandetron accelerator 3.8.2 Beam tuning at the Tandetron accelerator 3.8.3 The gamma-ray emission yield 3.8.4 Measurement setup 3.8.5 Energy detection 3.8.6 Spatial detection 3.8.7 Coincident timing 3.8.8 Coincident energy deposition 3.8.9 Detection efficiency η 3.8.10 Imaging setup 3.8.11 Image reconstruction 3.9 Implications for a therapeutic Compton imaging scenario 3.10 Summary and discussion 4 Prompt gamma-ray timing (PGT) 4.1 Theoretical description of PGT 4.1.1 Timing of prompt gamma-ray emission 4.1.2 Kinematics of protons 4.1.3 The correlation between spatial and temporal prompt gamma-ray emission in a thick target 4.1.4 Setup for time-resolved measurements of prompt gamma-rays 4.1.5 Uncertainty of the reference time 4.1.6 Standard error of the mean and confidence intervals of statistical momenta 4.1.7 A simplified MC method for the modeling of PGT 4.2 Experimental results 4.2.1 The GAGG detector 4.2.2 Detector energy resolution 4.2.3 Detector time resolution with 60-Co 4.2.4 Energy-resolved detector time resolution - the ELBE experiment 4.2.5 The KVI-CART proton beam line 4.2.6 Time-resolved measurement of prompt gamma-rays 4.2.7 Experimental determination of the system time resolution σ 4.2.8 PGT in dependence of proton transit time 4.3 Towards treatment verification with PGT 4.3.1 MC based PGT in dependence of proton range 4.3.2 MC based PGT at inhomogeneous targets 4.4 Implications for a therapeutic PGT scenario 4.4.1 Range verification for an exemplary PGT setup 4.4.2 Practical restrictions for the therapeutic PGT scenario 4.4.3 Principal limitations of the PGT method 4.5 Summary and outlook 5 Discussion Summary Zusammenfassung Bibliography Acknowledgement