Novel PET Systems and Image Reconstruction with Actively Controlled Geometry

Positron Emission Tomography (PET) provides in vivo measurement of imaging ligands that are labeled with positron emitting radionuclide. Since its invention, most PET scanners have been designed to have a group of gamma ray detectors arranged in a ring geometry, accommodating the whole patient body. Virtual Pinhole PET incorporates higher resolution detectors being placed close to the Region-of-Interest (ROI) within the imaging Field-of-View (FOV) of the whole-body scanner, providing better image resolution and contrast recover. To further adapt this technology to a wider range of diseases, we proposed a second generation of virtual pinhole PET using actively controlled high resolution detectors integrated on a robotic arm. When the whole system is integrated to a commercial PET scanner, we achieved positioning repeatability within 0.5 mm. Monte Carlo simulation shows that by focusing the high-resolution detectors to a specific organ of interest, we can achieve better resolution, sensitivity and contrast recovery. In another direction, we proposed a portable, versatile and low cost PET imaging system for Point-of-Care (POC) applications. It consists of one or more movable detectors in coincidence with a detector array behind a patient. The movable detectors make it possible for the operator to control the scanning trajectory freely to achieve optimal coverage and sensitivity for patient specific imaging tasks. Since this system does not require a conventional full ring geometry, it can be built portable and low cost for bed-side or intraoperative use. We developed a proof-of-principle prototype that consists of a compact high resolution silicon photomultiplier detector mounted on a hand-held probe and a half ring of conventional detectors. The probe is attached to a MicroScribe device, which tracks the location and orientation of the probe as it moves. We also performed Monte Carlo simulations for two POC PET geometries with Time-of-Flight (TOF) capability. To support the development of such PET systems with unconventional geometries, a fully 3D image reconstruction framework has been developed for PET systems with arbitrary geometry. For POC PET and the second generation robotic Virtual Pinhole PET, new challenges emerge and our targeted applications require more efficiently image reconstruction that provides imaging results in near real time. Inspired by the previous work, we developed a list mode GPU-based image reconstruction framework with the capability to model dynamically changing geometry. Ordered-Subset MAP-EM algorithm is implemented on multi-GPU platform to achieve fast reconstruction in the order of seconds per iteration, under practical data rate. We tested this using both experimental and simulation data, for whole body PET scanner and unconventional PET scanners. Future application of adaptive imaging requires near real time performance for large statistics, which requires additional acceleration of this framework

A Four-Dimensional Image Reconstruction Framework for PET under Arbitrary Geometries

Positron Emission Tomography (PET) is a functional imaging modality with applications ranging from the treatment of cancer, studying neurological diseases and disease models. Virtual-Pinhole PET technology improves the image quality in terms of resolution and contrast recovery. The technology calls for having a detector with smaller crystals placed near a region of interest in a conventional whole-body PET scanner. The improvement is from the higher spatial sampling of the imaging area near the detector. A prototype half-ring PET insert built to study head-and-neck cancer imaging was extended to breast cancer imaging. We have built a prototype half-ring PET insert for head-and-neck cancer imaging applications. In the first half of this work, we extend the use of the insert to breast imaging and show that such a system provides high resolution images of breast and axillary lymph nodes while maintaining the full imaging field of view capability of a clinical PET scanner. We are focused on designing unconventional PET geometries for specific applications. A general purpose 4D PET reconstruction framework was created to estimate the radionuclide uptake in the subject. Quantitative estimation in PET requires precise modeling of PET physics. Data acquired in a PET scanner is well modeled as a Poisson counting process. Reconstruction given the forward model is implemented using MAP-OSEM. The framework is capable of reconstructing PET data under arbitrary position of the detector elements and different crystal sizes. A novel symmetry finding algorithm is created to reduce the system matrix size, without loss of resolution. The framework motivates investigation into different PET system geometries for different applications, as well as optimizing the design of PET systems. A generalized normalization procedure was developed to model unknown components. The programs are parallelized using OpenMP and MPI to run on small workstations as well as super-computing clusters. The performance of our reconstruction framework is presented through four novel and unconventional PET systems, each designed specifically for a different geometry. The Virtual-Pinhole half-ring system is a half-ring insert integrated into a Siemens Biograph-40, for head and neck imaging. The Flat-panel system is a modular insert system integrated into the Biograph-40, designed for breast cancer imaging. The MicroInsert II is the second generation full ring insert device, integrated into the MicroPET scanner to improve the resolution and contrast recovery of the MicroPET scanner. The Plant PET system is a PET system designed to image plants vertically, and integrated into a plant growth chamber. The improvement in speed/memory from symmetry finding is as high as a factor of 50 in some cases. Further improvements to the framework and state of the field are also discussed

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

Preliminary Study of an Intra-operative PET Imaging Probe System.

PET imaging has gained widespread acceptance in cancer imaging because Positron Emission Tomography can identify physiological changes due to cancer. Nevertheless conventional PET imaging has difficulty detecting tumors less than 1cm in diameter in clinical use due mainly to background radiation, statistical noise, resolution loss due to lack of depth interaction resolution in detectors, and annihilation photon acolinearity. Conventionally if detected tumors are surgically removable, surgeons locate and remove the tumors during surgery based on the preoperative scans. One of the drawbacks of relying solely on preoperative imaging is that tumor locations could be displaced during surgery due to patient’s movement. In this dissertation, a preliminary study of an intra-operative PET imaging probe system is presented. The proposed probe system consists of a low resolution partial ring detector and a high resolution imaging probe that is equipped with a position tracker. The high resolution probe operates in coincidence with the partial ring detector. The high resolution imaging probe and its proximity to target lesions contribute to the localization of small tumors. In addition, the probe system can be used to detect occult tumors. The ultimate goal is to provide incremental 3-dimensional reconstructed images that are re-projected in real time onto a plane whose orientation is driven by the tracking device. A prototype of the PET imaging probe system was built to test the feasibility of the intra-operative PET imaging probe system. Coincidence detection efficiency of about 0.00012% was observed. A variant of 3-dimensional one-pass list-mode maximum likelihood algorithm (OP-LML) was developed to reconstruct images from the measured data. A row-action maximum likelihood algorithm was integrated with the OP-LML. To speed up image reconstruction by a factor of 30-40, the proposed algorithm was parallelized and was run on a graphics processing unit. Reconstructed images from simulated data with no intrinsic blurring showed resolution of 1.0mm~1.5mm FWHM. However as we expected, reconstructed images from the experimental set-up with limitations failed to separate two Na-22 point sources 1.5mm apart. Experimental resolutions of 4mm FWHM in the longitudinal direction and 2mm FWHM in the transverse direction were obtained for the two point sources.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86331/1/huhss_1.pd

Caracterización, mejora y diseño de escáneres PET preclínicos

El objetivo principal de esta tesis es contribuir a la mejora de la calidad de las imágenes de tomografía por emisión de positrones (PET) para la investigación preclínica con animales pequeños mediante el uso de simulaciones Monte Carlo, ya sea para el estudio de los problemas limitantes de la técnica en los escáneres existentes proporcionando métodos para compensarlos, ya sea para orientar el diseño de nuevos prototipos, analizando las ventajas y desventajas antes de tomar una decisión final. Los objetivos específicos son los siguientes: 1. Evaluar el rendimiento de los sistemas PET preclínicos disponibles en el Laboratorio de Imagen Médica, siguiendo, en la medida de lo posible, una metodología estándar para comparar los sistemas entre sí y con otros sistemas comerciales en las mismas condiciones [Vicente et al., 2006 , Goertzen et al., 2012, Vicente et al., 2010a]. 2. Estudiar las fuentes de error que limitan la calidad de las imágenes reconstruidas usando simulaciones Monte Carlo para investigar nuevos métodos y algoritmos para compensarlos [Vicente et al., 2012a, Abella et al., 2012, Vicente et al., 2010b]. 3. Utilizar simulaciones Monte Carlo para guiar el diseño de nuevos prototipos, realizando las modificaciones necesarias en el paquete de Monte Carlo empleado (peneloPET, [España et al., 2009]) y en los métodos de reconstrucción existentes (como GFIRST [Herraiz et al., 2011]) para adaptar los códigos existentes a la geometría no convencional de los nuevos diseños [Vicente et al., 2012b]. Todos los algoritmos desarrollados en el contexto de esta tesis no son exclusivos para un escáner en particular, sino que han sido diseñados para ser flexibles y fácilmente adaptables a diferentes arquitecturas que cumplan con ciertas condiciones en cada caso. Sin embargo, dado que este trabajo se beneficia del acceso a datos reales adquiridos por los escáneres disponibles en el Laboratorio de Imagen Médica, el desarrollo de los diferentes métodos se adaptan a la geometría particular de estos sistemas ([Wang et al., 2006b, Vaquero et al., 2005a]). Como consideración final, decir que una parte significativa de los resultados presentados en esta tesis, además de dar lugar a publicaciones científicas, se pretende que sean incorporados en el software de escáneres preclínicos de alta resolución fabricados por SEDECAL y distribuidos por todo el mundo en virtud de acuerdos de transferencia de tecnología con el Laboratorio de Imagen Médica y el Grupo de Física Nuclear (GFN). [ABSTRACT]The main goal of this thesis is to contribute to the improvement of the quality of positron emission tomography (PET) images for preclinical research with small animals by intensive use of Monte Carlo simulations, either for studying limiting problems in existing scanners providing methods to compensate them, either for guiding in the design of new prototypes, analyzing advantages and drawbacks before taking the final decision. Specific objectives are as follows: 1. To evaluate the performance of two of the small-animal PET systems available at the Medical Imaging Laboratory, following, as far as possible, a standard methodology in order to compare systems between them and with other commercial preclinical systems under similar conditions [Vicente et al., 2006 , Goertzen et al., 2012, Vicente et al., 2010a]. 2. To study the sources of error that limit the quality of reconstructed PET images using Monte Carlo simulations and to investigate new methods and algorithms to compensate for these errors [Vicente et al., 2011, Vicente et al., 2012a, Abella et al., 2012, Vicente et al., 2010b]. 3. To use Monte Carlo simulations for the design of new prototypes, performing the necessary modifications in the Monte Carlo package employed (peneloPET, [España et al., 2009]) and in the available reconstruction methods (as GFIRST [Herraiz et al., 2011]) in order to make them suitable to the non-conventional geometries of the new designs [Vicente et al., 2012b]. The algorithms developed in this thesis are not exclusive of any scanner in particular; they have been designed to be flexible and suitable for different architectures with only a few common constrains. However, since this work takes advantage of the access to real data collected by the specific systems available at the Medical Imaging Laboratory, the development and testing of the different methods were adapted to the particular geometry of these systems ([Wang et al., 2006b, Vaquero et al., 2005a]). As a final consideration, it is worth mentioning that significant part of the results presented in this thesis, besides giving rise to scientific publications, are intended to be incorporated into the preclinical high-resolution systems manufactured by SEDECAL and distributed worldwide under technology transfer agreements with the Medical Imaging Laboratory and the Nuclear Physics Group

The potential use of cerium-doped lanthanum scintillators and optimisation of imaging processing in SPECT

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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

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