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Hadron therapy is a radiotherapy modality which offers a precise energy deposition to the tumors and a dose reduction to healthy tissue as compared to conventional methods. However, methods for real-time monitoring are required to ensure that the radiation dose is deposited on the target. The IRIS group of IFIC-Valencia developed a Compton camera prototype for this purpose, intending to image the Prompt Gammas emitted by the tissue during irradiation. The system detectors are composed of Lanthanum (III) bromide scintillator crystals coupled to silicon photomultipliers. After an initial characterization in the laboratory, in order to assess the system capabilities for future experiments in proton therapy centers, different tests were carried out in two facilities: PARTREC (Groningen, The Netherlands) and the CNA cyclotron (Sevilla, Spain). Characterization studies performed at PARTREC indicated that the detectors linearity was improved with respect to the previous version and an energy resolution of 5.2 % FWHM at 511 keV was achieved. Moreover, the imaging capabilities of the system were evaluated with a line source of 68Ge and a point-like source of 241Am-9Be. Images at 4.439 MeV were obtained from irradiation of a graphite target with an 18 MeV proton beam at CNA, to perform a study of the system potential to detect shifts at different intensities. In this sense, the system was able to distinguish 1 mm variations in the target position at different beam current intensities for measurement times of 1800 and 600 s.

The use of Compton cameras for medical imaging and its interest as a hadron therapy treatment monitoring has increased in the last decade with the development of silicon photomultipliers. MACACO is a Compton camera prototype designed and assembled at the IRIS group of IFIC-Valencia. This Compton camera is based on monolithic Lanthanum (III) Bromide crystals and silicon photomultipliers, and employs the novel TOFPET2 ASIC as readout electronics. This system emerged as an alternative to MACACO II prototype, with the aim of improving its limited time resolution. To test the performance of the ASIC in a Compton camera setup, the prototype was characterized, both in laboratory and in-beam. A time resolution of 1.5 ns was obtained after time corrections, which improves greatly the performance of the MACACO II. Moreover, the results obtained at high photon energies demonstrate the ability of the system to obtain 1 mm displacements of the reconstructed spots. The results reinforce the potential of the system as a monitoring device for hadron therapy.

Compton cameras can offer advantages over gamma cameras for some applications, since they are well suited for multitracer imaging and for imaging high-energy radiotracers, such as those employed in radionuclide therapy. While in conventional clinical settings state-of-the-art Compton cameras cannot compete with well-established methods such as PET and SPECT, there are specific scenarios in which they can constitute an advantageous alternative. The combination of PET and Compton imaging can benefit from the improved resolution and sensitivity of current PET technology and, at the same time, overcome PET limitations in the use of multiple radiotracers. Such a system can provide simultaneous assessment of different radiotracers under identical conditions and reduce errors associated with physical factors that can change between acquisitions. Advances are being made both in instrumentation developments combining PET and Compton cameras for multimodal or three-gamma imaging systems, and in image reconstruction, addressing the challenges imposed by the combination of the two modalities or the new techniques. This review article summarizes the advances made in Compton cameras for medical imaging and their combination with PET.

The invention relates to a solution for determining events related to photons and charged particles useful in therapies that use methodologies related to hadron therapy. In one aspect of the invention, it relates to a device having a sandwich-type structure of photon-detecting panels (1) and charged particle-detecting panels (2), which can be suitably associated with respective sensors. Also included is a method for detecting photons and charged particles that uses the aforementioned device. Lastly, a specific use of the object of the invention in hadron therapy is described.

El CSIC presenta sus nuevos prototipos tecnológicos y empresas de base tecnológica en el 11º Foro Transfiere de Málaga, la gran cita de la innovación en España que se celebró el 16 y 17 de febrero. Los nuevos prototipos consisten en robots para la vendimia, cámaras para monitorizar combustible nuclear y con aplicaciones en instalaciones médicas, y un dispositivo de fotones con aplicaciones en el tratamiento de enfermedades como el cáncer, entre otros. Además, el CSIC presenta empresas de base tecnológica como Datision, que ofrece una tecnología que recoge datos para conocer el impacto de escaparates comerciales.

[ES] Se detalla una solución para la determinación de eventos relacionados con fotones y partículas cargadas de utilidad en terapias que hacen uso de metodologías relacionadas con la hadrónica. En un aspecto de la invención se tiene un dispositivo que presenta una estructura tipo sándwich de paneles detectores de fotones (1) y paneles detectores de partículas cargadas (2) que pueden estar convenientemente asociados a respectivos sensores. Asimismo, se incluye un método para detección de fotones y partículas cargadas que hace uso del citado dispositivo. Finalmente, se detalla un uso concreto del objeto de la invención en terapia hadrónica., [EN] A solution is detailed for the determination of events related to photons and charged particles useful in therapies that make use of methodologies related to hadronics. In one aspect of the invention there is a device that has a sandwich-type structure of photon detector panels (1) and charged particle detector panels (2) that can be conveniently associated with respective sensors. Also included is a method for detecting photons and charged particles that makes use of the aforementioned device. Finally, a specific use of the object of the invention in hadronic therapy is detailed.

[EN] Described is a solution for determining events related to photons and charged particles useful in therapies that employ methodologies related to hadron therapy. In one aspect, the invention relates to a device having a sandwich-type structure of photon-detecting panels (1) and charged-particle-detecting panels (2), which can be suitably associated with respective sensors. Also included is a method for detecting photons and charged particles, which uses the device. Lastly, a specific use of the subject matter of the invention in hadron therapy is described, [ES] Se detalla una solución para la determinación de eventos relacionados con fotones y partículas cargadas de utilidad en terapias que hacen uso de metodologías relacionadas con la hadrónica. En un aspecto de la invención se tiene un dispositivo que presenta una estructura tipo sándwich de paneles detectores de fotones (1) y paneles detectores de partículas cargadas (2) que pueden estar convenientemente asociados a respectivos sensores. Asimismo, se incluye un método para detección de fotones y partículas cargadas que hace uso del citado dispositivo. Finalmente, se detalla un uso concreto del objeto de la invención en terapia hadrónica, [FR] L'invention concerne une solution pour déterminer des événements associés à des photons et des particules chargées utiles dans des thérapies qui utilisent des méthodologies associées à l'hadronique. Dans un aspect, l'invention concerne un dispositif qui présente une structure de type sandwich de panneaux détecteurs de photons (1) et de panneaux détecteurs de particules chargées (2) qui peuvent être associés de manière appropriée à des capteurs respectifs. L'invention concerne également un procédé pour la détection de photons et de particules chargées qui fait appel audit dispositif. Enfin, l'invention détaille l'utilisation concrète de l'objet de l'invention en thérapie hadronique

The applicability extent of hadron therapy for tumor treatment is currently limited by the lack of reliable online monitoring techniques. An active topic of investigation is the research of monitoring systems based on the detection of secondary radiation produced during treatment. MACACO, a multi-layer Compton camera based on LaBr scintillator crystals and SiPMs, is being developed at IFIC-Valencia for this purpose. This work reports the results obtained from measurements of a 150 MeV proton beam impinging on a PMMA target. A neural network trained on Monte Carlo simulations is used for event selection, increasing the signal to background ratio before image reconstruction. Images of the measured prompt gamma distributions are reconstructed by means of a spectral reconstruction code, through which the 4.439 MeV spectral line is resolved. Images of the emission distribution at this energy are reconstructed, allowing calculation of the distal fall-off and identification of target displacements of 3 mm.

The IRIS group at IFIC-Valencia has developed a second version of a Compton camera prototype for hadron therapy treatment monitoring, with the aim of improving the performance with respect to its predecessor. The system is composed of three Lanthanum (III) bromide (LaBr) crystals coupled to silicon photomultipliers (SiPMs). The detector energy resolution has been improved to 5.6% FWHM at 511 keV and an angular resolution of 8.0° has been obtained. Images of a Na point-like source have been reconstructed selecting two and three interaction events. Moreover, the experimental data have been reproduced with Monte Carlo simulations using a Compton camera module (CCMod) in GATE v8.2 obtaining a good correlation.

Compton cameras are gamma-ray imaging systems which have been proposed for a wide variety of applications such as medical imaging, nuclear decommissioning or homeland security. In the design and optimization of such a system Monte Carlo simulations play an essential role. In this work, we propose a generic module to perform Monte Carlo simulations and analyses of Compton Camera imaging which is included in the open-source GATE/Geant4 platform. Several digitization stages have been implemented within the module to mimic the performance of the most commonly employed detectors (e.g. monolithic blocks, pixelated scintillator crystals, strip detectors...). Time coincidence sorter and sequence coincidence reconstruction are also available in order to aim at providing modules to facilitate the comparison and reproduction of the data taken with different prototypes. All processing steps may be performed during the simulation (on-the-fly mode) or as a post-process of the output files (offline mode). The predictions of the module have been compared with experimental data in terms of energy spectra, angular resolution, efficiency and back-projection image reconstruction. Consistent results within a 3-sigma interval were obtained for the energy spectra except for low energies where small differences arise. The angular resolution measure for incident photons of 1275 keV was also in good agreement between both data sets with a value close to 13°. Moreover, with the aim of demonstrating the versatility of such a tool the performance of two different Compton camera designs was evaluated and compared.

One factor limiting the current applicability extent of hadron therapy is the lack of a reliable method for real time treatment monitoring. The use of Compton imaging systems as monitors requires the correct reconstruction of the distribution of prompt gamma productions during patient irradiation. In order to extract the maximum information from all the measurable events, we implemented a spectral reconstruction method that assigns to all events a probability of being either partial or total energy depositions. The method, implemented in a list-mode maximum likelihood expectation maximization algorithm, generates a four dimensional image in the joint spatial-spectral domain, in which the voxels containing the emission positions and energies are obtained. The analytical model used for the system response function is also employed to derive an analytical expression for the sensitivity, which is calculated via Monte Carlo integration. The performance of the method is evaluated through reconstruction of various experimental and simulated sources with different spatial and energy distributions. The results show that the proposed method can recover the spectral and spatial information simultaneously, but only under the assumption of ideal measurements. The analysis of the Monte Carlo simulations has led to the identification of two important degradation sources: the mispositioning of the gamma interaction point and the missing energy recorded in the interaction. Both factors are related to the high energy transferred to the recoil electrons, which can travel far from the interaction point and even escape the detector. These effects prevent the direct application of the current method in more realistic scenarios. Nevertheless, experimental point-like sources have been accurately reconstructed and the spatial distributions and spectral emission of complex simulated phantoms can be identified.

The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in proton therapy. The system is composed of three detector planes, each made of a [Formula: see text] monolithic crystal coupled to a SiPM array. Having obtained successful results with the first prototype (MACACO) that demonstrated the feasibility of the proposed technology, a second prototype (MACACO II) with improved performance has been developed, and is the subject of this work. The new system has an enhanced detector energy resolution which translates into a higher spatial resolution of the telescope. The image reconstruction method has also been improved with an accurate model of the sensitivity matrix. The device has been tested with high energy photons at the National Accelerator Centre (CNA, Seville). The tests involved a proton beam of 18 MeV impinging on a graphite target, to produce 4.4 MeV photons. Data were taken at different system positions of the telescope with the first detector at 65 and 160 mm from the target, and at different beam intensities. The measurements allowed successful reconstruction of the photon emission distribution at two target positions separated by 5 mm in different telescope configurations. This result was obtained both with data recorded in the first and second telescope planes (two interaction events) and, for the first time in beam experiments, with data recorded in the three planes (three interaction events).

Un factor que limita el ámbito de aplicación de la terapia hadrónica es la falta de un sistema fiable de monitorización en tiempo real. Entre otros posibles métodos que están siendo investigados, las cámaras Compton son un candidato para lograr dicha monitorización. En el marco del proyecto MACACO, el grupo IRIS ha desarrollado un prototipo de cámara Compton compacta y reconfigurable, que consta de dos o tres planos detectores basados en cristales centelleadores de LaBr3 acoplados a matrices de SiPMs. Esta tesis recoge mi investigación llevada a cabo dentro del proyecto MACACO, al cual he contribuido principalmente en dos aspectos: la evaluación del funcionamiento del dispositivo experimental y el desarrollo del software de reconstrucción empelado para el análisis y la reconstrucción de imágenes a partir de los datos medidos.

Purpose Real-time monitoring is still a challenge in hadrontherapy. With this aim, a Compton telescope prototype (MACACO) has been developed by the IRIS group at IFIC-Valencia within the European project ENVISION. The second prototype MACACO II is an upgrade developed with the purpose of enhancing its performance. Material and Methods MACACO II consists of three layers of LaBr3 monolithic crystals coupled to silicon photomultiplier (SiPM) arrays. New crystals have been coupled to 8x8 pixel SiPM arrays from Hamamatsu Photonics (S13361-3050AE-08). Moreover, an improved image reconstruction code including an accurate model for the sensitivity matrix has been implemented. The telescope has been characterized in the laboratory with 22Na and 152Eu sources and tested in two accelerator centres. The first test took place at CNA (Sevilla) with a 18 MeV proton beam impinging on a graphite target in order to produce 4.4 MeV gamma rays. A second test was held in KVI-CART (Groningen) with a 150 MeV proton beam hitting a PMMA target. Monte Carlo simulations have been carried out with GATE V 7.0. Results In the laboratory, the energy resolution has been improved and an angular resolution of 4.6° has been achieved, which together with the improved reconstruction code, have led to a better image quality. The efficiency measured with two planes in coincidence at 1275 keV is 1.0x10-3. Monte Carlo simulations result in a good correlation with the experimental parameters. Regarding the In-beam experiments, two target positions separated by 5 mm have been reconstructed from the CNA test-beam. Furthermore, KVI-CART test-beam results show that Bragg distribution correlates to the PMMA position. Conclusions MACACO II has shown a better performance than the previous prototype. The testbeam results have demonstrated the ability to reconstruct different positions. Further improvements are ongoing in order to achieve the required performance for the application.

Hadron therapy (HT) is a technique used in cancer treatment that consists in the irradiation of tumours using light ions or protons instead of photons. HT treatment monitoring in real-time is one of the main challenges addressed nowadays. The IRIS group (http://ific.uv.es/iris) at IFIC-Valencia is developing a Compton telescope with this purpose. The system is made of three LaBr3 detector planes coupled to silicon photomultipliers (SiPMs). A first prototype (MACACO: Medical Applications CompAct COmpton camera) was successfully developed, with promising results. A second version has been developed with the aim of improving the system performance, including new detectors for the first two planes and an improved image reconstruction code, improving significantly the performance tests in laboratory and accelerator facilities. The performance improvement of MACACO II was verified through experimental tests. In addition, Monte Carlo simulations were made with GATE v 7.0 getting a good correlation with the experimental measurements. In this poster we present results corresponding to the two-layer layout with the new detectors.

The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in ion beam therapy. The system is composed of three detector planes, each made of a LaBr 3 monolithic crystal coupled to SiPM arrays. The first prototype (MACACO), was fully characterised in the laboratory and in beam tests demonstrating the feasibility of the proposed technology. A second prototype (MACACO II), described in this work, is currently being developed to improve performance. The SiPM arrays have been replaced by newer models, leading to an improved detector energy resolution which translates into a higher spatial resolution of the telescope. In addition, the image reconstruction code has been improved with an accurate model of the sensitivity matrix. Furthermore, a new spectral reconstruction algorithm for Compton cameras with two planes has been developed showing promising results. The system has been fully characterised in the laboratory at controlled temperature and also tested in two accelerator facilities. The first involved a proton beam of 18 MeV impinging a graphite target. The results allowed the successful reconstruction of two target positions separated by 5 mm. The second test beam used protons of 150 MeV impinging on a PMMA target. The results show that for measurements taken in different positions of the PMMA target the reconstructed Bragg peak position is related to the PMMA position.

1. Dispositivo de adquisición de datos para dispositivos detectores de diferentes tipos, comprende: una primera placa auxiliar (P_AUX) que incluye: - un primer dispositivo detector (1), de un primer tipo; - una pluralidad de chips de lectura (2) operativamente conectada a dicho primer dispositivo detector (1) para adquirir dichos datos proporcionando una única señal de salida de los datos adquiridos; y - una unidad de conexión (5); y - una placa principal (P_PRIN) que incluye: - una unidad de control (14) adaptada para procesar datos; y - una unidad de conexión (10), para conexión de la placa principal (P_PRIN) con un dispositivo de computación remoto para transmitir a este último los datos procesados y recibir de él diferentes comandos, caracterizado porque el dispositivo comprende, además: - al menos una segunda placa auxiliar (P_AUX) que incluye: - un segundo dispositivo detector (1), de un segundo tipo, diferente del primer tipo; - una pluralidad de chips de lectura (2) operativamente conectada a dicho segundo dispositivo detector (1) para adquirir dichos datos proporcionando una única señal de salida de los datos adquiridos, y - una unidad de conexión (5), estando conectada al menos una de las placas auxiliares (P_AUX) a una placa intermedia (P_INT), conectada a su vez a la placa principal (P_PRIN), en donde dicha placa intermedia (P_INT), que es al menos una, incluye: - una primera unidad de conexión (6) configurada para recibir la señal única de salida de los datos adquiridos, de su placa auxiliar correspondiente; - una unidad de ajuste (7) configurada para adaptarla señal única de salida recibida a un protocolo de comunicación de la placa principal (P_PRIN); y - una segunda unidad de conexión (8) configurada para transmitir la señal adaptada a la placa principal (P_PRIN) y para recibir de esta última diferentes comandos; y porque - la placa principal (P_PRIN) incluye además un dispositivo de disparo (13) configurado para detectar cuando las señales únicas de

The IRIS group at IFIC Valencia is developing a three-layer Compton camera for treatment monitoring in ion beam therapy. The system is composed of three detector planes, each made of a LaBr3 monolithic crystal coupled to SiPM arrays. The first prototype (MACACO) was fully characterised in the laboratory and in beam tests demonstrating the feasibility of the proposed technology. A second prototype (MACACO II), described in this work, is currently being developed to improve performance. The SiPM arrays have been replaced by newer models, leading to an improved detector energy resolution which translates into a higher spatial resolution of the telescope. A new coincidence board allows acquisition of data with any two or all three detectors simultaneously. In addition, the image reconstruction code has been improved with an accurate model of the sensitivity matrix. The device has also been tested in two accelerator facilities. The first involved a proton beam of 18 MeV impinging a graphite target. The results allowed the successful reconstruction of two target positions separated by 5 mm. The second test beam used protons of 150 MeV impinging on a PMMA target. Preliminary analysis results show prompt-gamma energy spectra as expected for these proton energies. Analysis of this data is ongoing, with the aim of reconstructing the Bragg peak profilein the PMMA target. Further improvements to the readout electronics are also underway.

Given the strong variations in the sensitivity of Compton cameras for the detection of events originating from different points in the field of view (FoV), sensitivity correction is often necessary in Compton image reconstruction. Several approaches for the calculation of the sensitivity matrix have been proposed in the literature. While most of these models are easily implemented and can be useful in many cases, they usually assume high angular coverage over the scattered photon, which is not the case for our prototype. In this work, we have derived an analytical model that allows us to calculate a detailed sensitivity matrix, which has been compared to other sensitivity models in the literature. Specifically, the proposed model describes the probability of measuring a useful event in a two-plane Compton camera, including the most relevant physical processes involved. The model has been used to obtain an expression for the system and sensitivity matrices for iterative image reconstruction. These matrices have been validated taking Monte Carlo simulations as a reference. In order to study the impact of the sensitivity, images reconstructed with our sensitivity model and with other models have been compared. Images have been reconstructed from several simulated sources, including point-like sources and extended distributions of activity, and also from experimental data measured with Na sources. Results show that our sensitivity model is the best suited for our prototype. Although other models in the literature perform successfully in many scenarios, they are not applicable in all the geometrical configurations of interest for our system. In general, our model allows to effectively recover the intensity of point-like sources at different positions in the FoV and to reconstruct regions of homogeneous activity with minimal variance. Moreover, it can be employed for all Compton camera configurations, including those with low angular coverage over the scatterer.

El trabajo presentado en esta tesis introduce y evalúa dos aspectos novedosos en los detectores de rayos gamma para imagen médica: el uso de fotomultiplicadores de silicio (SiPMs, en inglés) acoplados a cristales centelleadores continuos. Tradicionalmente, los tubos fotomultiplicadores (PMTs, en inglés) acoplados a cristales centelleadores han jugado un papel dominante en la detección de rayos gamma. En los últimos años ha aparecido un nuevo tipo de fotodetector de estado sólido, el SiPM, como opción para sustituir a los PMTs en ciertas aplicaciones. Los SiPMs tienen una ganancia y una eficiencia cuántica altas, un voltaje de operación bajo y unas propiedades temporales excelentes. Además, son dispositivos muy compactos e insensibles a los campos magnéticos. Estas propiedades hacen de los SiPMs un excelente candidato para usarlos en aplicaciones de física médica. Normalmente, la detección de los rayos gamma se lleva a cabo utilizando detectores basados en cristales centelleadores pixelados acoplados a un fotodetector segmentado porque ofrecen una manera sencilla de identificar el lugar donde ha tenido lugar la interacción. Sin embargo, en esta configuración la mejora de la resolución espacial implica la reducción de la sensibilidad, y al revés. El uso de cristales centelleadores continuos acoplados a SiPMs podría aumentar la resolución espacial y la sensibilidad al mismo tiempo, además de reducir el coste del bloque detector. El trabajo presentado se desarrolló en el grupo IRIS (Image Reconstruction, Instrumentation and Simulations for medical applications) del IFIC-Valencia. Se inició cuando el uso de los SiPMs estaba empezando y llevó a desarrollos importantes. En esta tesis, se han probado diferentes tipos de cristales centelleadores continuos acoplados a SiPMs de varios fabricantes para demostrar la viabilidad de esta tecnología en el desarrollo de nuevos conceptos de detector y aplicaciones en física médica. La mayor parte de la tesis tra ...