Development Of A Scintillation Detector And The Influence On Clinical Imaging

The detector is the functional unit within a Positron Emission Tomography (PET) scanner, serving to convert the energy of radiation emitted from a patient into positional information, and as such contributes significantly to the performance of the scanner. While modern whole-body scanners use detectors composed of very many (i.e., 20000-30000) small pixels, typically ~4x4x20mm3 in size, several groups are actively investigating the performance of continuous crystals coupled to position sensitive photodetectors as an alternative detector design with a number of potential advantages, including improved spatial resolution and position sampling. This work in particular focuses on thick (≥14mm) continuous crystals in order to maintain the sensitivity of modern scanners. Excellent spatial resolution in continuous detectors that are thick, however, has proven difficult to achieve using simple positioning algorithms, leading to research in the field to improve performance. This thesis aims to investigate the effect of modifications to the scintillation light spread within the bulk of the scintillator to improve performance, focusing on the use of laser induced optical barriers (LIOBs) etched within thick continuous crystals, and furthermore aims to translate the effect on detector performance to scanner quantitation in patient studies. The conventional continuous detector is first investigated by analyzing the various components of the detector as well as its limitations. It is seen that the performance of the detector is affected by a number of variables that either cannot be improved or may be improved only at the expense of greater complexity or computing time; these include the photodetector, the positioning algorithm, and Compton scatter in the detector. The performance of the detectors, however, is fundamentally determined by the light spread within the detector, and limited by the depth-dependence of the light spread and poor performance in the entrance region, motivating efforts to modify this aspect of the detector. The feasibility and potential of LIOBs to fine-tune this light spread and improve these limitations is then studied using both experiments and simulations. The behavior of the LIOBs in response to optical light is investigated, and the opacity of the etchings is shown to be dependent on the parameters of the etching procedure. Thick crystals were also etched with LIOBs in their entrance region in a grid pattern in order to improve the resolution in the entrance region. Measurements show an overall improvement in spatial resolution: the resolution in the etched region of the crystals is slightly improved (e.g., ~0.8mm for a 25mm thick crystal), though in the unetched region, it is slightly degraded (e.g., ~0.4mm for a 25mm thick crystal). While the depth-dependence of the response of the crystal is decreased, the depth-of-interaction (DOI) performance is degraded as well. Simulation studies informed by these measurements show that the properties of the LIOBs strongly affect the performance of the crystal, and ultimately further illustrate that trade-offs in spatial resolution, position sampling, and DOI resolution are inherent in varying the light spread using LIOBs in this manner; these may be used as a guide for future experiments. System Monte Carlo simulations were used to investigate the added benefit of improved detector spatial resolution and position sampling to the imaging performance of a whole-body scanner. These simulations compared the performance of scanners composed of conventional pixelated detectors to that of scanners using continuous crystals. Results showed that the improved performance (relative to that of 4-mm pixelated detectors) of continuous crystals with a 2-mm resolution, pertinent to both the etched 14mm thick crystal studied as well as potential designs with the etched 25mm thick crystal, increased the mean contrast recovery coefficient (CRC) of images by ~22% for 5.5mm spheres. Last, a set of experiments aimed to test the correspondence between quantification in phantom and patient images using a lesion embedding methodology, so that any improvements determined using phantom studies may be understood clinically. The results show that the average CRC values for lesions embedded in the lung and liver agree well with those for lesions embedded in the phantom for all lesion sizes. In addition, the relative changes in CRC resulting from application of post-filters on the subject and phantom images are consistent within measurement uncertainty. This study shows that the improvements in CRC resulting from improved spatial resolution, measured using phantom studies in the simulations, are representative of improvements in quantitative accuracy in patient studies. While unmodified thick continuous detectors hold promise for both improved image quality and quantitation in whole-body imaging, excellent performance requires intensive hardware and computational solutions. Laser induced optical barriers offer the ability to modify the light spread within the scintillator to improve the intrinsic performance of the detector: while measurements with crystals etched with relatively transmissive etchings show a slight improvement in resolution, simulations show that the LIOBs may be fine-tuned to result in improved performance using relatively simple positioning algorithms. For systems in which DOI information is less important, and transverse resolution and sensitivity are paramount, etching thick detectors with this design, fine-tuned to the particular thickness of the crystal and application, is an interesting alternative to the standard detector design

Reconstruction Algorithms for Novel Joint Imaging Techniques in PET

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types. The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules, and tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to low positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (Simultaneous Beta-Gamma Imager). The imager can simultaneously detect positrons (β+) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs the beta and gamma images independently to estimate the thickness component of the beta forward model, and then jointly estimates the radioactivity distribution in the object. We have validated the physics model and the reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the Structural Similarity (SSIM) index for comparing the leaf images from the Simultaneous Beta-Gamma Imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively. The second case is the virtual-pinhole PET technology, which has shown that higher resolution and contrast recovery can be gained by adding a high resolution PET insert with smaller crystals to a conventional PET scanner. Such enhancements are obtained when the insert is placed in proximity of the region of interest (ROI) and in coincidence with the conventional PET scanner. Intuitively, the insert may be positioned within the scanner\u27s axial field-of-view (FOV) and radially closer to the ROI than the scanner\u27s ring. One of the complicating factors of this design is the insert\u27s blocking the scanner\u27s lines-of-response (LORs). Such data may be compensated through attenuation and scatter correction in image reconstruction. However, a potential solution is to place the insert outside of the scanner\u27s axial FOV and to move the body to be in proximity of the insert. We call this imaging strategy the surveillance mode. As the main focus of this work, we have developed an image reconstruction framework for the surveillance mode imaging. The preliminary results show improvement in spatial resolution and contrast recovery. Any improvement in contrast recovery should result in enhancement in tumor detectability, which will be of high clinical significance

Reconstruction Algorithms for Novel Joint Imaging Techniques in PET

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types. The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules, and tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to low positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (Simultaneous Beta-Gamma Imager). The imager can simultaneously detect positrons (β+) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs the beta and gamma images independently to estimate the thickness component of the beta forward model, and then jointly estimates the radioactivity distribution in the object. We have validated the physics model and the reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the Structural Similarity (SSIM) index for comparing the leaf images from the Simultaneous Beta-Gamma Imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively. The second case is the virtual-pinhole PET technology, which has shown that higher resolution and contrast recovery can be gained by adding a high resolution PET insert with smaller crystals to a conventional PET scanner. Such enhancements are obtained when the insert is placed in proximity of the region of interest (ROI) and in coincidence with the conventional PET scanner. Intuitively, the insert may be positioned within the scanner\u27s axial field-of-view (FOV) and radially closer to the ROI than the scanner\u27s ring. One of the complicating factors of this design is the insert\u27s blocking the scanner\u27s lines-of-response (LORs). Such data may be compensated through attenuation and scatter correction in image reconstruction. However, a potential solution is to place the insert outside of the scanner\u27s axial FOV and to move the body to be in proximity of the insert. We call this imaging strategy the surveillance mode. As the main focus of this work, we have developed an image reconstruction framework for the surveillance mode imaging. The preliminary results show improvement in spatial resolution and contrast recovery. Any improvement in contrast recovery should result in enhancement in tumor detectability, which will be of high clinical significance

Development of a silicon photomultiplier based innovative and low cost positron emission tomography scanner.

The Silicon Photomultiplier (SiPM) is a state-of-the-art semiconductor photodetector consisting of a high density matrix (up to 104) of independent pixels of micro-metric dimension (from 10 μm to 100 μm) which form a macroscopic unit of 1 to 6 mm2 area. Each pixel is a single-photon avalanche diode operated with a bias voltage of a few volts above the breakdown voltage. When a charge carrier is generated in a pixel by an incoming photon or a thermal effect, a Geiger discharge confined to that pixel is initiated and an intrinsic gain of about 106 is obtained. The output signal of a pixel is the same regardless of the number of interacting photons and provide only a binary information. Since the pixels are arranged on a common Silicon substrate and are connected in parallel to the same readout line, the SiPM combined output response corresponds to the sum of all fired pixel currents. As a result, the SiPM as a whole is an analogue detector, which can measure the incoming light intensity. Nowadays a great number of companies are investing increasing efforts in SiPM detector performances and high quality mass production. SiPMs are in rapid evolution and benefit from the tremendous development of the Silicon technology in terms of cost production, design flexibility and performances. They have reached a high single photon detection sensitivity and photon detection efficiency, an excellent time resolution, an extended dynamic range. They require a low bias voltage and have a low power consumption, they are very compact, robust, flexible and cheap. Considering also their intrinsic insensitivity to magnetic field they result to have an extremely high potential in fundamental and applied science (particle and nuclear physics, astrophysics, biology, environmental science and nuclear medicine) and industry. The SiPM performances are influenced by some effects, as saturation, afterpulsing and crosstalk, which lead to an inherent non-proportional response with respect to the number of incident photons. Consequently, it is not trivial to relate the measured electronic signal to the corresponding light intensity. Since for most applications it is desirable to qualify the SiPM response (i.e in order to properly design a detector for a given application, perform corrections on measurements or on energy spectra, calibrate a SiPM for low light measurements, predict detector performance) the implementation of characterization procedures plays a key role. The SiPM field of application that has been considered in this thesis is the Positron Emission Tomography (PET). PET represents the most advanced in-vivo nuclear imaging modality: it provides functional information of the physiological and molecular processes of organs and tissues. Thanks to its diagnostic power, PET has a recognized superiority over all other imaging modalities in oncology, neurology and cardiology. SiPMs are usually successfully employed for the PET scanners because they allow the measurement of the Time Of Flight of the two coincidence photons to improve the signal to noise ratio of the reconstructed images. They also permit to perfectly combine the functional information with the anatomical one by inserting the PET scanner inside the Magnetic Resonance Imaging device. Recently, PET technology has also been applied to preclinical imaging to allow non invasive studies on small animals. The increasing demand for preclinical PET scanner is driven by the fact that small animals host a large number of human diseases. In-vivo imaging has the advantage to enable the measurement of the radiopharmaceutical distribution in the same animal for an extended period of time. As a result, PET represents a powerful research tool as it offers the possibility to study the abnormalities at the origin of a disease, understand its dynamics, evaluate the therapeutic response and develop new drugs and treatments. However, the cost and the complexity of the preclinical scanners are limiting factors for the spread of PET technology: 70-80% of small-animal PET is concentrated in academic or government research laboratories. The EasyPET concept proposed in this Thesis, protected under a patent filed by Aveiro University, aims to achieve a simple and affordable preclinical PET scanner. The innovative concept is based on a single pair of detector kept collinear during the whole data acquisition and a moving mechanism with two degrees of freedom to reproduce the functionalities of an entire PET ring. The main advantages are in terms of the reduction of the complexity and cost of the PET system. In addition the concept is bound to be robust against acollinear photoemission, scatter radiation and parallax error. The sensitivity is expected to represent a fragility due to the reduced geometrical acceptance. This drawback can be partially recovered by the possibility to accept Compton scattering events without introducing image degradation effects, thanks to the sensor alignment. A 2D imaging demonstrator has been realized in order to assess the EasyPET concept and its performance has been analyzed in this Thesis to verify the net balance between competing advantages and drawbacks. The demonstrator had a leading role in the outreach activity to promote the EasyPET concept and a significant outcome is represented by the new partners that recently joined the collaboration. The EasyPET has been licensed to Caen S.p.a. and, thanks to the participation of Nuclear Instruments to the electronic board re-designed, a new prototype has been realized with additional improvements concerning the mechanics and the control software. In this Thesis the prototype functionalities and performances are reported as a result of a commissioning procedure. The EasyPET will be commercialized by Caen S.p.a. as a product for the educational market and it will be addressed to high level didactic laboratories to show the operating principles and technology behind the PET imaging. The topics mentioned above will be examined in depth in the following Chapters according to the subsequent order. In Chapter 1 the Silicon Photomultiplier will be described in detail, from their operating principle to their main application fields passing through the advantages and the drawback effects connected with this type of sensor. Chapter 2 is dedicated to a SiPM standard characterization method based on the staircase and resolving power measurement. A more refined analysis involves the Multi-Photon spectrum, obtained by integrating the SiPM response to a light pulse. It exploits the SiPM single photon sensitivity and its photon number resolving capability to measure some of its properties of general interest for a multitude of potential applications, disentangling the features related to the statistics of the incident light. Chapter 3 reports another SiPM characterization method which implements a post-processing of the digitized SiPM waveforms with the aim of extracting a full picture of the sensor characteristics from a unique data-set. The procedure is very robust, effective and semi-automatic and suitable for sensors of various dimensions and produced by different vendors. Chapter 4 introduces the Positron Emission Tomography imaging: its principle, applications, related issues and state of the art of PET scanner will be explained. Chapter 5 deals with the preclinical PET, reporting the benefits and the technological challenges involved, the performance of the commercially available small animal PET scanners, the main applications and the frontier research in this field. In Chapter 6 the EasyPET concept is introduced. In particular, the basic idea behind the operating principle, the design layout and the image reconstruction will be illustrated and then assessed through the description and the performance analysis of the EasyPET proof of concept and demonstrator. The effect of the use of different sensor to improve the light collection and the coincidence detection efficiency, together with the analysis of the importance of the sensor and the crystal alignment will be reported in Chapter 7. The design, the functionalities and the commissioning of the EasyPET prototype addressed to the educational market will be defined in Chapter 8. Finally, Chapter 9 contains a summary of the conclusions and an outlook of the future research studies

Improvements in Cardiac Spect/CT for the Purpose of Tracking Transplanted Cells

Regenerative therapy via stem cell transplantation has received increased attention to help treat the myocardial injury associated with heart disease. Currently, the hybridisation of SPECT with X-ray CT is expanding the utility of SPECT. This thesis compared two SPECT/CT systems for attenuation correction using slow or fast-CT attenuation maps (mu-maps). We then developed a method to localize transplanted cells in relation to compromised blood flow in the myocardium following a myocardial infarction using SPECT/CT. Finally, a method to correct for image truncation was studied for a new SPECT/CT design that incorporated small field-of-view (FOV) detectors. Computer simulations compared gated-SPECT reconstructions using slow-CT and fast-CT mu-maps with gated-CT mu-maps. Using fast-CT mu-maps improved the Root Mean Squared (RMS) error from 4.2% to 4.0%. Three canine experiments were performed comparing SPECT/CT reconstruction using the Infinia/Hawkeye-4 (slow-CT) and Symbia T6 (fast-CT). Canines were euthanized prior to imaging, and then ventilated. The results showed improvements in both RMS errors and correlation coefficients for all canines. A first-pass contrast CT imaging technique can identify regions of myocardial infarction and can be fused with SPECT. Ten canines underwent surgical ligation of the left-anterior-descending artery. Cells were labeled with 111In-tropolone and transplanted into the myocardium. SPECT/CT was performed on day of transplantation, 4, and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed and successfully delineated the infarct zone. Delayed-enhanced MRI was performed and correlated well with first-pass CT. Contrast-to-noise ratios were calculated for 111In-SPECT and suggested that cells can be followed for 11 effective half-lives. We evaluated a modified SPECT/CT acquisition and reconstruction method for truncated SPECT. Cardiac SPECT/CT scans were acquired in 14 patients. The original projections were truncated to simulate a small FOV acquisition. Data was reconstructed in three ways: non-truncated and standard reconstruction (NTOSEM), which was our gold-standard; truncated and standard reconstruction (TOSEM); and truncated and a modified reconstruction (TMOSEM). Compared with NTOSEM, small FOV imaging incurred an average cardiac count ratio error greater than 100% using TOSEM and 8.9% using TMOSEM. When we plotted NTOSEM against TOSEM and TMOSEM the correlation coefficient was 0.734 and 0.996 respectively

Development of a silicon photomultiplier based innovative and low cost positron emission tomography scanner.

The Silicon Photomultiplier (SiPM) is a state-of-the-art semiconductor photodetector consisting of a high density matrix (up to 104) of independent pixels of micro-metric dimension (from 10 \u3bcm to 100 \u3bcm) which form a macroscopic unit of 1 to 6 mm2 area. Each pixel is a single-photon avalanche diode operated with a bias voltage of a few volts above the breakdown voltage. When a charge carrier is generated in a pixel by an incoming photon or a thermal effect, a Geiger discharge confined to that pixel is initiated and an intrinsic gain of about 106 is obtained. The output signal of a pixel is the same regardless of the number of interacting photons and provide only a binary information. Since the pixels are arranged on a common Silicon substrate and are connected in parallel to the same readout line, the SiPM combined output response corresponds to the sum of all fired pixel currents. As a result, the SiPM as a whole is an analogue detector, which can measure the incoming light intensity. Nowadays a great number of companies are investing increasing efforts in SiPM detector performances and high quality mass production. SiPMs are in rapid evolution and benefit from the tremendous development of the Silicon technology in terms of cost production, design flexibility and performances. They have reached a high single photon detection sensitivity and photon detection efficiency, an excellent time resolution, an extended dynamic range. They require a low bias voltage and have a low power consumption, they are very compact, robust, flexible and cheap. Considering also their intrinsic insensitivity to magnetic field they result to have an extremely high potential in fundamental and applied science (particle and nuclear physics, astrophysics, biology, environmental science and nuclear medicine) and industry. The SiPM performances are influenced by some effects, as saturation, afterpulsing and crosstalk, which lead to an inherent non-proportional response with respect to the number of incident photons. Consequently, it is not trivial to relate the measured electronic signal to the corresponding light intensity. Since for most applications it is desirable to qualify the SiPM response (i.e in order to properly design a detector for a given application, perform corrections on measurements or on energy spectra, calibrate a SiPM for low light measurements, predict detector performance) the implementation of characterization procedures plays a key role. The SiPM field of application that has been considered in this thesis is the Positron Emission Tomography (PET). PET represents the most advanced in-vivo nuclear imaging modality: it provides functional information of the physiological and molecular processes of organs and tissues. Thanks to its diagnostic power, PET has a recognized superiority over all other imaging modalities in oncology, neurology and cardiology. SiPMs are usually successfully employed for the PET scanners because they allow the measurement of the Time Of Flight of the two coincidence photons to improve the signal to noise ratio of the reconstructed images. They also permit to perfectly combine the functional information with the anatomical one by inserting the PET scanner inside the Magnetic Resonance Imaging device. Recently, PET technology has also been applied to preclinical imaging to allow non invasive studies on small animals. The increasing demand for preclinical PET scanner is driven by the fact that small animals host a large number of human diseases. In-vivo imaging has the advantage to enable the measurement of the radiopharmaceutical distribution in the same animal for an extended period of time. As a result, PET represents a powerful research tool as it offers the possibility to study the abnormalities at the origin of a disease, understand its dynamics, evaluate the therapeutic response and develop new drugs and treatments. However, the cost and the complexity of the preclinical scanners are limiting factors for the spread of PET technology: 70-80% of small-animal PET is concentrated in academic or government research laboratories. The EasyPET concept proposed in this Thesis, protected under a patent filed by Aveiro University, aims to achieve a simple and affordable preclinical PET scanner. The innovative concept is based on a single pair of detector kept collinear during the whole data acquisition and a moving mechanism with two degrees of freedom to reproduce the functionalities of an entire PET ring. The main advantages are in terms of the reduction of the complexity and cost of the PET system. In addition the concept is bound to be robust against acollinear photoemission, scatter radiation and parallax error. The sensitivity is expected to represent a fragility due to the reduced geometrical acceptance. This drawback can be partially recovered by the possibility to accept Compton scattering events without introducing image degradation effects, thanks to the sensor alignment. A 2D imaging demonstrator has been realized in order to assess the EasyPET concept and its performance has been analyzed in this Thesis to verify the net balance between competing advantages and drawbacks. The demonstrator had a leading role in the outreach activity to promote the EasyPET concept and a significant outcome is represented by the new partners that recently joined the collaboration. The EasyPET has been licensed to Caen S.p.a. and, thanks to the participation of Nuclear Instruments to the electronic board re-designed, a new prototype has been realized with additional improvements concerning the mechanics and the control software. In this Thesis the prototype functionalities and performances are reported as a result of a commissioning procedure. The EasyPET will be commercialized by Caen S.p.a. as a product for the educational market and it will be addressed to high level didactic laboratories to show the operating principles and technology behind the PET imaging. The topics mentioned above will be examined in depth in the following Chapters according to the subsequent order. In Chapter 1 the Silicon Photomultiplier will be described in detail, from their operating principle to their main application fields passing through the advantages and the drawback effects connected with this type of sensor. Chapter 2 is dedicated to a SiPM standard characterization method based on the staircase and resolving power measurement. A more refined analysis involves the Multi-Photon spectrum, obtained by integrating the SiPM response to a light pulse. It exploits the SiPM single photon sensitivity and its photon number resolving capability to measure some of its properties of general interest for a multitude of potential applications, disentangling the features related to the statistics of the incident light. Chapter 3 reports another SiPM characterization method which implements a post-processing of the digitized SiPM waveforms with the aim of extracting a full picture of the sensor characteristics from a unique data-set. The procedure is very robust, effective and semi-automatic and suitable for sensors of various dimensions and produced by different vendors. Chapter 4 introduces the Positron Emission Tomography imaging: its principle, applications, related issues and state of the art of PET scanner will be explained. Chapter 5 deals with the preclinical PET, reporting the benefits and the technological challenges involved, the performance of the commercially available small animal PET scanners, the main applications and the frontier research in this field. In Chapter 6 the EasyPET concept is introduced. In particular, the basic idea behind the operating principle, the design layout and the image reconstruction will be illustrated and then assessed through the description and the performance analysis of the EasyPET proof of concept and demonstrator. The effect of the use of different sensor to improve the light collection and the coincidence detection efficiency, together with the analysis of the importance of the sensor and the crystal alignment will be reported in Chapter 7. The design, the functionalities and the commissioning of the EasyPET prototype addressed to the educational market will be defined in Chapter 8. Finally, Chapter 9 contains a summary of the conclusions and an outlook of the future research studies

Design and implementation of PET detectors based on monolithic crystals and SiPMs

Esta tesis doctoral se centra tanto en el diseño como en la validación experimental de detectores de rayos gamma para escáneres de tomografía por emisión de positrones (PET, del inglés Positron Emission Tomography). El objetivo principal de esta tesis es el diseño de innovadores bloques detectores PET de alto rendimiento. La técnica PET constituye una de las principales herramientas diagnósticas en medicina nuclear, que es una especialidad médica que utiliza sustancias radiactivas con fines diagnósticos y terapéuticos. Esta técnica de imagen médica permite visualizar procesos fisiológicos y bioquímicos del cuerpo humano in vivo, mediante la administración del elemento radiotrazador. Los radiotrazadores son compuestos químicos, similares a las sustancias naturales del cuerpo, en las que uno o más átomos son sustituidos por radionúclidos emisores de fotones, para su uso en gamma cámaras y SPECT, o de positrones (la antipartícula del electrón) para PET. En el primer capítulo de la tesis se introducen las principales técnicas de imagen médicas utilizadas en la actualidad, incluyendo las técnicas de imagen funcional, de imagen anatómica y su fusión para dar lugar a imágenes multimodales. En el segundo capítulo, dado que la técnica PET es el foco de estudio central de la tesis, se describe en detalle su historia mostrando los avances de los últimos 60 años, hasta establecerse en la actualidad como una herramienta diagnóstica imprescindible en medicina. En este capítulo se describen también los principios físicos de la técnica, los algoritmos de reconstrucción y las correcciones de imagen que se emplean. Así mismo el capítulo describe el papel fundamental del tiempo de vuelo de los fotones producidos en la aniquilación del positrón y el electrón, y de la coordenada de profundidad de interacción (DOI, del inglés Depth of Interaction). A continuación, en el tercer capítulo, se describen con detalle los materiales y métodos empleados en PET, haciendo especial énfasis en aquellos utilizados para el desarrollo de esta tesis. En la actualidad, la mayoría de sistemas PET comerciales están constituidos por bloques detectores basados en cristales centelleadores pixelados (matrices de pequeños cristales). Dichos cristales permiten estimar las coordenadas (x, y) del impacto del fotón de manera sencilla, sin embargo, la obtención de la coordenada de profundidad de interacción (z), imprescindible para obtener una buena resolución espacial sobretodo en los bordes del campo de visión del escáner, resulta una tarea difícil que requiere el uso de materiales adicionales y por tanto incrementan el precio del escáner. Una alternativa a la configuración anterior, es el uso de cristales monolíticos o continuos los cuales están constituidos por una única pieza de material centelleador que permite “observar” la distribución de fotones ópticos generada. Esta información es utilizada para obtener con precisión las coordenadas 3D de impacto del fotón (x, y, z) en el cristal sin necesidad de otros materiales. Por este motivo, en esta tesis doctoral se ha llevado a cabo el diseño de detectores basados en estos cristales monolíticos acoplados a fotosensores de estado sólido compatibles con equipos de resonancia magnética. En este capítulo se muestran los resultados obtenidos en la caracterización de diferentes tipos de cristales, geometrías y tratamientos aplicados a la superficie de los bloques detectores. Finalmente se presenta una breve descripción de los equipos que han motivado los estudios realizados en la tesis. Dado que el formato de esta tesis esta basado en un compendio de los artículos más relevantes publicados durante el transcurso de los estudios de doctorado, el cuarto capítulo incluye una copia de los artículos publicados más relevantes tal y como se muestran en las revistas científicas. Se presentan un total de 6 artículos que recogen los principales resultados obtenidos durante los estudios de doctorado. Dada la calidad de los resultados globales obtenidos, dos de los bloques detectores diseñados constituyen la base de dos sistemas PET dedicados al estudio del cerebro humano, el inserto MINDView (proyecto europeo FP7) y el escáner CareMiBrain (proyecto europeo Horizont 2020). El equipo MINDView, que es un inserto compatible con todas las resonancias magnéticas del mundo, ha sido instalado en el hospital de la Universidad Técnica de Múnich y actualmente está en la fase previa a comenzar un estudio con pacientes. En la tesis se recogen las pruebas de validación realizadas tanto a nivel del bloque detector como del equipo final. Respecto al equipo CareMiBrain, que es un escáner PET dedicado al estudio del Alzheimer y de otras enfermedades de deterioro cognitivo, ha sido instalado en Madrid y los primeros pacientes ya han sido escaneados satisfactoriamente. En la tesis se recoge el diseño y los resultados de caracterización del bloque detector. Además del diseño y caracterización de dichos bloques detectores, se muestran también los resultados y conclusiones obtenidas en otros estudios de investigación, tales como la caracterización de una gran variedad de geometrías de detectores, la optimización de la extracción de la luz en cristales BGO (fueron pioneros en los equipos PET pero se sustituyeron por los nuevos cristales que son más rápidos), tanto en forma pixelada como en bloques monolíticos, y un enfoque de detector híbrido que utiliza capas monolíticas y pixeladas en un mismo bloque detector. Se ha prestado especial atención a la caracterización y determinación de la DOI dentro de los bloques monolíticos, reduciendo el error de paralaje en la imagen final reconstruida. El quinto capítulo contiene un resumen y conclusiones de los resultados de esta tesis. El sexto y séptimo capítulo, contienen un resumen en castellano y valenciano respectivamente, de los objetivos, motivación, materiales, métodos, resultados y conclusiones de la tesis doctoral. Finalmente, el Apéndice A muestra una lista completa de los artículos científicos publicados durante la tesis (incluyendo los seleccionados para el compendio).This doctoral thesis focuses on both the design and experimental validation of gamma-ray detectors suitable for Positron Emission Tomography (PET) scanners. The main objective is the design of high efficiency PET detector blocks. The PET technique constitutes one of the main diagnostic tools in Nuclear Medicine, which is a medical specialty that uses radioactive substances for diagnostic and therapeutic purposes. This Medical Imaging technique allows one to visualize physiological and biochemical processes of the human body in vivo, by means of the administration of a radiotracer element. Radiotracers are chemical compounds, similar to the body's natural substances, in which one or more atoms are replaced by radionuclides that emit photons, for use in gamma and SPECT cameras, or positrons (the antiparticle of the electron) for PET. The first chapter of the thesis introduces the main Medical Imaging techniques that are currently used, including functional and anatomical imaging as well as their possible merging generating multimodal images. In the second chapter, since PET imaging is the focus of this thesis, an extensive description of this technique is outlined. The chapter begins with a brief history of PET, showing the advances over the last 60 years until being established as an essential diagnostic tool in medicine. This chapter also describes the physical principles of PET, the reconstruction algorithms and the applied image corrections techniques. In addition to the basic concepts, the role of Time of Flight (TOF) and DOI in PET are described in this chapter. The third chapter describes in detail the materials and methods used in PET, making special emphasis on those used for the development of this work. Currently, most commercial PET systems consist of detector blocks based on pixelated scintillation crystals (matrices of small crystals). These crystals allow one for an easy estimation of the planar impact coordinates of the gamma-ray within the crystal (x, y). However, estimating the depth of interaction coordinate (z), which is essential to obtain a good spatial resolution especially at the edges of the field of view of the scanner, is a difficult task that requires the use of extra materials and therefore increases the price of the scanner. An alternative to that configuration is the use of monolithic crystals, which are constituted by a single piece of scintillating material that permits to characterize the complete, flashing light distribution. This information is used to obtain the 3D impact coordinates of the photon (x, y, z) within the crystal with high resolution and without the need for extra materials. For this reason, this doctoral thesis focusses on the design of PET detector blocks based on monolithic crystals coupled to solid state photosensors. These components are compatible with magnetic fields and therefore, suitable for their simultaneous use with Magnetic Resonance Imaging (MRI) systems. This chapter summarizes the results obtained in the characterization of different types of crystals, geometries and treatments applied to the crystal surface of the detector blocks. Finally, a brief description of the PET systems that have motivated the studies carried out in the thesis is presented. Since this thesis is based on a compendium of the most relevant articles published during the course of the PhD studies, Chapter 4 presents a copy of those research articles, as exactly shown in the different per-reviewed journals, including a brief introduction highlighting their main results. A total of 6 articles are presented, which contain the main results obtained during the doctoral studies. Given the quality of the overall obtained results, two of the designed detector blocks have been selected as the basis of two PET systems dedicated to the study of the human brain namely, i) the MINDView insert (European Union FP7 project) and, ii) the CareMiBrain stand-alone scanner (European Union project Horizon 2020). The MINDView system, which is a PET insert compatible with MRI scanners, has been installed at Technical University of Munich and is currently starting scanning patients with depression and schizophrenia. The thesis includes the validation tests carried out at the level of the detector block and of the final equipment. The CareMiBrain system, which is a PET scanner dedicated to the study of the Alzheimer disease and other causes of cognitive decline, has been installed in a hospital in Madrid and the first patients have already been successfully scanned. The thesis contains the design and results of characterization of the CareMiBrain detector block. In addition to the design and characterization of those detector blocks, other research studies have been carried out during the course of this thesis, such as the characterization of a large variety of photosensor geometries, the optimization of light extraction in BGO crystals, both in pixelated and monolithic geometries, and a hybrid detector approach that uses monolithic and pixellated layers in the same detector block. Special emphasis has been given to the characterization and estimation of the DOI coordinate within monolithic blocks, reducing the parallax error in the reconstructed final image. Chapter 5 contains a summary of the results and conclusions of this thesis. Chapters 6 and 7 summarize, in Spanish and Valencian, respectively, the objectives, motivation, materials, methods, results and conclusions of this doctoral thesis. A complete list of all the per-reviewed articles (including those selected for this compendium) and the conference proceedings published during the development of this thesis can be found in Appendix A

Simulation of Clinical PET Studies for the Assessment of Quantification Methods

On this PhD thesis we developed a methodology for evaluating the robustness of SUV measurements based on MC simulations and the generation of novel databases of simulated studies based on digital anthropomorphic phantoms. This methodology has been applied to different problems related to quantification that were not previously addressed. Two methods for estimating the extravasated dose were proposed andvalidated in different scenarios using MC simulations. We studied the impact of noise and low counting in the accuracy and repeatability of three commonly used SUV metrics (SUVmax, SUVmean and SUV50). The same model was used to study the effect of physiological muscular uptake variations on the quantification of FDG-PET studies. Finally, our MC models were applied to simulate 18F-fluorocholine (FCH) studies. The aim was to study the effect of spill-in counts from neighbouring regions on the quantification of small regions close to high activity extended sources

A Monte Carlo study of the accuracy of CT-numbers for range calculations in carbon ion therapy

Kohlenstoffionen deponieren den größten Teil ihrer Energie in einer schmalen Region nahe der maximalen Reichweite (Bragg Peak). Die Reichweite der Ionen in Gewebe ist abhängig von der Elektronendichte des Gewebes. Diese Elektronendichte kann gegenwärtig nur mit Hilfe eines Röntgen-Computertomographen (CT) mit ausreichend räumlicher Auflösung gemessen werden. Daher ist es notwendig, möglichst exakte CT-Daten zu erhalten. Diese CT-Daten sind allerdings abhängig von den Parametern die während der Datenerfassung verwendet werden. In dieser Arbeit wird der Einfluss dieser Messparameter auf die CT-Daten mit Hilfe von Monte-Carlo Simulationen einzelner CT-Projektionen und der Rekonstruktion dieser Projektionen systematisch studiert. Abweichungen der CT-Daten aufgrund des Phantomdurchmessers sowie der Zusammensetzung des Substitutmaterials, dem verwendeten Phantommaterial und der gewählten Spannung der CT-Röntgenröhre werden untersucht. Desweiteren wird die Übertragung von Unsicherheiten in den CT-Daten in eine herapeutisch relevantere Reichweiten- und Dosisunsicherheit bei der Anwendung von Kohlenstoffstrahlen diskutiert