京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20786号 / 理博第4330号 / 新制||理||1622(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 谷森 達, 教授 永江 知文, 教授 鶴 剛 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

In dieser Arbeit wird die Bildgebung durch eine Compton-Kamera zur Überwachung der Partikelstrahlentherapie erstmals an der Technischen Universität Dresden untersucht. Die inhärenten Beschränkungen der Methode wurden durch Berechnungen und Monte Carlo Simulationen studiert. Im Zuge dieser Untersuchungen erschien der Raumtemperatur-Halbleiter Cadmium Zink Tellurid als ein vielversprechendes Detektor-Material. Zur weiteren Untersuchung wurde eine einfache Compton-Kamera konstruiert bestehend aus einem Cadmium Zink Tellurid Detektor und einem ortsempfndlichen Szintillationsdetektor. Das System hat gezeigt, dass eine akkurate Bildgebung mit radioaktiven Punktquellen unter Laborbedingungen möglich ist. Weitere praktische Beschränkungen der Compton-Bildgebung unter Strahlbedingungen konnten durch Experimente an einem Protonen-Strahl hergeleitet werden. Durch die experimentellen Erfahrungen mit der in dieser Arbeit entwickelten Compton-Kamera konnten wertvolle Informationen gesammelt werden, die erlauben, die Bildrekonstruktion zu evaluieren und dazu beitragen, die weitere Forschung hin zu einer klinisch anwendbaren Compton-Kamera zu leiten. / This work presents the first efforts at the Dresden University of Technology to study the feasibility of Compton imaging as a modality to monitor ion beam radiation therapy. The inherent limitations of the method have been studied by means of calculation and Monte Carlo simulation. As a result, the room-temperature semiconductor cadmium zinc telluride appeared as a promising detector material for a clinical device. For more detailed investigation, a simple Compton camera has been constructed comprising a cadmium zinc telluride detector and a position sensitive scintillation detector. This system has proven that accurate imaging of radioactive point sources in the laboratory is feasible. More practical restrictions of Compton imaging in beam conditions have been derived through experiments at a proton facility. Through the experimental work with the Compton camera developed in this work, valuable information was gathered which allowed to test the image reconstruction and to direct the further research towards a clinical Compton camera system.

Medical imaging is a technique that allows us to visualize non surgically the internal structure of the human body in order to diagnose or treat medical conditions. It permits also monitoring of physical processes or functions of different organs inside the body. The medical imaging encompasses wide range of techniques based on different physical prin- ciples, including techniques using ionizing radiation. The quality of the images depends significantly on the quality of the used imaging detectors. There are many types of the detectors, from old analog devices (e.g. films) to fully digital detectors such as flat panels, that are the most widely used today. The newer technology is being developed and the techniques such as photon counting explored. However, the state of the art technology is the single photon counting, where the experimental detectors such as Medipix are able to count and process each individual photon. This works studies the properties, features and applications of the newest detector from the Medipix family Timepix3 in different imaging modalities. Firstly, a design of a new hardware readout interface for Timepix3 is presented together with data acquisition software and new analysis and calibration algorithms. Then, different applications of Timepix3 detector were explored: very...

In dieser Arbeit wird die Bildgebung durch eine Compton-Kamera zur Überwachung der Partikelstrahlentherapie erstmals an der Technischen Universität Dresden untersucht. Die inhärenten Beschränkungen der Methode wurden durch Berechnungen und Monte Carlo Simulationen studiert. Im Zuge dieser Untersuchungen erschien der Raumtemperatur-Halbleiter Cadmium Zink Tellurid als ein vielversprechendes Detektor-Material. Zur weiteren Untersuchung wurde eine einfache Compton-Kamera konstruiert bestehend aus einem Cadmium Zink Tellurid Detektor und einem ortsempfndlichen Szintillationsdetektor. Das System hat gezeigt, dass eine akkurate Bildgebung mit radioaktiven Punktquellen unter Laborbedingungen möglich ist. Weitere praktische Beschränkungen der Compton-Bildgebung unter Strahlbedingungen konnten durch Experimente an einem Protonen-Strahl hergeleitet werden. Durch die experimentellen Erfahrungen mit der in dieser Arbeit entwickelten Compton-Kamera konnten wertvolle Informationen gesammelt werden, die erlauben, die Bildrekonstruktion zu evaluieren und dazu beitragen, die weitere Forschung hin zu einer klinisch anwendbaren Compton-Kamera zu leiten.:Abstract/Zusammenfassung Illustration Index Index of Tables List of Abbreviations 0 Introduction 0.1 Motivation 0.2 Task 1 Physical Background 1.1 Interaction of Ionizing Radiation with Matter 1.1.1 Coherent Photon Scattering 1.1.2 Incoherent Photon Scattering 1.1.3 Complete Absorption in the Nuclear Electric Field 1.1.4 Pair Production 1.1.5 Total Photon Cross Section 1.1.6 Directly Ionizing Radiation 1.2 Prompt Gamma-rays from Nuclear Reactions 1.3 Detector Technology 1.3.1 Semiconductor Detectors 1.3.2 Scintillation Detectors 1.4 Compton Imaging 1.4.1 Image Formation 1.4.2 History and Application of Compton Cameras 1.5 Prompt Gamma-ray Imaging for In-vivo Dosimetry – Work of Other Groups 2 Design Study 2.1 Introduction 2.1.1 Emission Spectra – Available Data 2.2 Materials and Methods 2.2.1 Angular Resolution 2.2.2 Efficiency 2. Results 2.4 Conclusions 3 Prototype System 3.1 Overview 3.2 System Components 3.2.1 CdZnTe Detector and its Front-end-electronics 3.2.2 LSO Block-Detector 3.2.3 Mounting Frame 3.2.4 DAQ Hardware and Software 3.3 Results 3.3.1 Detector Performance 3.3.2 System Performance 3.4 Conclusions 4 Beam Experiments 4.1 Introduction 4.2 Materials and Methods 4.3 Results 4.3.1 Source Test 4.3.2 Beam Profile 4.3.3 Trigger Rate 4.3.4 Pixel Selection in the LSO 4.3.5 Phantom Measurement 4.4 Conclusions 5 Discussion Appendix A A.1 Technical Drawing of the CdZnTe Electrode Layout Bibliography Danksagung Erklärung / This work presents the first efforts at the Dresden University of Technology to study the feasibility of Compton imaging as a modality to monitor ion beam radiation therapy. The inherent limitations of the method have been studied by means of calculation and Monte Carlo simulation. As a result, the room-temperature semiconductor cadmium zinc telluride appeared as a promising detector material for a clinical device. For more detailed investigation, a simple Compton camera has been constructed comprising a cadmium zinc telluride detector and a position sensitive scintillation detector. This system has proven that accurate imaging of radioactive point sources in the laboratory is feasible. More practical restrictions of Compton imaging in beam conditions have been derived through experiments at a proton facility. Through the experimental work with the Compton camera developed in this work, valuable information was gathered which allowed to test the image reconstruction and to direct the further research towards a clinical Compton camera system.:Abstract/Zusammenfassung Illustration Index Index of Tables List of Abbreviations 0 Introduction 0.1 Motivation 0.2 Task 1 Physical Background 1.1 Interaction of Ionizing Radiation with Matter 1.1.1 Coherent Photon Scattering 1.1.2 Incoherent Photon Scattering 1.1.3 Complete Absorption in the Nuclear Electric Field 1.1.4 Pair Production 1.1.5 Total Photon Cross Section 1.1.6 Directly Ionizing Radiation 1.2 Prompt Gamma-rays from Nuclear Reactions 1.3 Detector Technology 1.3.1 Semiconductor Detectors 1.3.2 Scintillation Detectors 1.4 Compton Imaging 1.4.1 Image Formation 1.4.2 History and Application of Compton Cameras 1.5 Prompt Gamma-ray Imaging for In-vivo Dosimetry – Work of Other Groups 2 Design Study 2.1 Introduction 2.1.1 Emission Spectra – Available Data 2.2 Materials and Methods 2.2.1 Angular Resolution 2.2.2 Efficiency 2. Results 2.4 Conclusions 3 Prototype System 3.1 Overview 3.2 System Components 3.2.1 CdZnTe Detector and its Front-end-electronics 3.2.2 LSO Block-Detector 3.2.3 Mounting Frame 3.2.4 DAQ Hardware and Software 3.3 Results 3.3.1 Detector Performance 3.3.2 System Performance 3.4 Conclusions 4 Beam Experiments 4.1 Introduction 4.2 Materials and Methods 4.3 Results 4.3.1 Source Test 4.3.2 Beam Profile 4.3.3 Trigger Rate 4.3.4 Pixel Selection in the LSO 4.3.5 Phantom Measurement 4.4 Conclusions 5 Discussion Appendix A A.1 Technical Drawing of the CdZnTe Electrode Layout Bibliography Danksagung Erklärung

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20172号 / 理博第4257号 / 新制||理||1612(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 谷森 達, 教授 永江 知文, 教授 鶴 剛 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Compton cameras localize γ-ray sources in 3D space by observing evidence of Compton scattering with detectors sensitive to ionizing radiation. This thesis proposes a software system for operating a novel Compton camera device comprised of Timepix3 detectors and Katherine readouts. To communicate with readouts using UDP-based protocol, a dedicated hardware library was developed. The presented software can successfully control the acquisition of multiple Timepix3 detectors and simultaneously process their measurements in a real-time setting. To recognize instances of Compton scattering among observed interactions, a chain of algorithms is applied with explicit consideration for a possibly high volume of measured information. Unlike alternate approaches, the presented work uses a recently published charge drift time model to improve its spatial resolution. In order to achieve localization of γ-ray sources, the software performs conical back projection into a discretized cuboid volume. Results of randomized evaluation with simulated data indicate that the presented implementation is correct and constitutes a viable method of γ-ray source localization in 3D space. Experimental verification with a prototype model is in progress.

L'hadronthérapie est une technique innovante de radiothérapie par ions carbone ou protons visant à améliorer les traitements actuels. La précision balistique accrue renforce la nécessité d'un contrôle du dépôt de dose, si possible en temps réel. Une manière de réaliser ce contrôle est de détecter avec une caméra Compton le gamma prompt émis lors des fragmentations nucléaires pendant l'irradiation du patient. Dans un premier temps, la géométrie de deux types de caméra Compton (double diffusion puis simple diffusion) a été optimisée par simulation Monte Carlo. Cette optimisation a été réalisée en étudiant la réponse des caméras à une source ponctuelle de photons avec un spectre en énergie réaliste. La réponse de la caméra optimisée à l'irradiation d'un fantôme d'eau par un faisceau d'ions carbone ou de protons a ensuite été simulée. Ces simulations ont tout d'abord été confrontées à des mesures effectuées avec un prototype de taille réduite. Ces mesures ont ensuite été utilisées pour évaluer les taux de comptage dans les détecteurs attendus en conditions cliniques. Dans la configuration actuelle de la caméra, ces taux sont élevés et les phénomènes d'empilement risquent d'être problématiques. Enfin, il est démontré que le dispositif étudié est sensible à un déplacement du pic de Bragg de plus ou moins 5 mm malgré les problèmes de coïncidences fortuites et malgré le bruit introduit par l'algorithme de reconstruction utilisé. / Ion beam therapy is an innovative radiotherapy technique using mainly carbon ion and proton irradiations. Its aim is to improve the current treatment modalities. Because of the sharpness of the dose distributions, a control of the dose if possible in real time is highly desirable. A possibility is to detect the prompt gamma rays emitted subsequently to the nuclear fragmentations occurring during the treatment of the patient. In a first time two different Compton cameras (double and single scattering) have been optimised by means of Monte Carlo simulations. The response of the camera to a photon point source with a realistic energy spectrum was studied. Then, the response of the camera to the irradiation of a water phantom by a proton beam was simulated. It was first compared with measurement performed with small-size detectors. Then, using the previous measurements, we evaluated the counting rates expected in clinical conditions. In the current set-up of the camera, these counting rates are pretty high. Pile up and random coincidences will be problematic. Finally we demonstrate that the detection system is capable to detect a longitudinal shift in the Bragg peak of +or- 5 mm, even with the current reconstruction algorithm.

Les travaux décrits dans cette thèse sont centrés sur la caractérisation et l’optimisation d’une camera Compton à phase unique au xénon liquide pour des applications médicales. Le détecteur a été conçu pour exploiter les avantages d’une technique d’imagerie médicale innovante appelée l’imagerie 3γ. Elle vise à l’obtention de la position en 3D d’une source radioactive avec une très haute sensibilité et une réduction importante de la dose administrée au patient. L’imagerie 3γ est basée sur la détection en coïncidence de 3 photons gamma émis par un émetteur spécifique (+β, γ), le 44Sc. Un premier prototype de camera Compton au xénon liquide a été développé par le laboratoire Subatech à travers le projet XEMIS (Xenon Medical Imaging System), pour démontrer la faisabilité de l’imagerie 3γ. Ce nouveau système de détection comporte un système de cryogénie avancé et une électronique front-end à très faible bruit qui fonctionne à la température du xénon liquide. Ce travail a contribué à la caractérisation de la réponse du détecteur et à l’optimisation de la mesure du signal d’ionisation. L'influence de la grille de Frisch sur le signal mesuré a été particulièrement étudiée. Les premières preuves de la reconstruction Compton en utilisant une source de ²²Na (β+, Eγ = 1.274 MeV) sont aussi rapportées dans cette thèse et valident la preuve de concept de la faisabilité de l’imagerie 3γ. Les résultats présentés dans cette thèse ont joué un rôle essentiel dans le développement d’une camera Compton au xénon liquide de grandes dimensions pour l’imagerie des petits animaux. Ce nouveau détecteur, appelée XEMIS2, est maintenant en phase de construction. / The work described in this thesis is focused on the characterization and optimization of a single-phaseliquid xenon Compton camera for medical imaging applications. The detector has been conceived to exploit the advantages of an innovative medical imaging technique called 3γ imaging, which aims to obtain aprecise 3D location of a radioactive source with high sensitivity and an important reduction of the dose administered to the patient. The 3γ imaging technique is based on the detection in coincidence of 3gamma rays emitted by a specific (+β, γ) emitter radionuclide,the 44Sc. A first prototype of a liquid xenon Compton camera has been developed by Subatech laboratory within the XEMIS (Xenon Medical Imaging System) project, to proof the feasibility of the 3γ imaging technique. This new detection framework is based on an advanced cryogenic system and an ultra-low noise front-end electronics operating at liquid xenon temperature. This work has contributed to the characterization of the detector response and the optimization of the ionization signal extraction. A particular interest has been given to the influence of the Frisch grid on the measured signals. First experimental evidences of the Compton cone reconstruction using asource of ²²Na (β+, Eγ = 1.274 MeV) are also reported in this thesis, which demonstrate the proof of concept of the feasibility of the 3γ imaging. The results reported in this thesis have been essential for the development of a larger scale liquid xenon Compton camera for small animal imaging. This new detector, called XEMIS2, is now in phase of construction.

Ion beam therapy is an innovative radiotherapy technique using mainly carbon ion and proton irradiations. Its aim is to improve the current treatment modalities. Because of the sharpness of the dose distributions, a control of the dose if possible in real time is highly desirable. A possibility is to detect the prompt gamma rays emitted subsequently to the nuclear fragmentations occurring during the treatment of the patient. In a first time two different Compton cameras (double and single scattering) have been optimised by means of Monte Carlo simulations. The response of the camera to a photon point source with a realistic energy spectrum was studied. Then, the response of the camera to the irradiation of a water phantom by a proton beam was simulated. It was first compared with measurement performed with small-size detectors. Then, using the previous measurements, we evaluated the counting rates expected in clinical conditions. In the current set-up of the camera, these counting rates are pretty high. Pile up and random coincidences will be problematic. Finally we demonstrate that the detection system is capable to detect a longitudinal shift in the Bragg peak of +or- 5 mm, even with the current reconstruction algorithm.

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.