Multi-Isotope Multi-Pinhole SPECT Bildgebung in kleinen Labortieren: Experimentelle Messungen und Monte Carlo Simulationen

Single photon emission computed tomography (SPECT) in small laboratory animals has become an integral part of translational medicine. It enables non-invasive validation of drug targeting, safety and efficacy in living organisms, which is progressively gaining importance in pharmaceutical industry. The increasing demand for efficiency in pharmaceutical research could be addressed by novel multitracer study designs. Multi-isotope multi-pinhole sampling allows validation of multiple tracers in a single experiment and consolidation of consecutive research trials. Due to physical and technical limitations, however, image quality and quantification can be substantially reduced. Advanced corrective procedures are required to establish multi-isotope multi-pinhole SPECT as a reliable and quantitative imaging technique for widespread use. For this purpose, the present work aimed to investigate the technical capabilities and physical limitations of multi-isotope multi-pinhole SPECT imaging in small laboratory animals. Based on experimental measurements and Monte Carlo simulations, specific error sources have been identified and procedures for quantitative image correction have been developed. A Monte Carlo simulation model of a state-of-the art SPECT/CT system has been established to provide a generalized framework for in-silico optimization of imaging hardware, acquisition protocols and reconstruction algorithms. The findings of this work can be used to improve image quality and quantification of SPECT in-vivo data for multi-isotope applications. They guide through the laborious process of multi-isotope protocol optimization and support the 3R welfare initiative that aims to replace, reduce and refine animal experimentation.Die Einzelphotonen-Emissionscomputertomographie (SPECT) in kleinen Labortieren hat sich als wichtiger Bestandteil der translationalen Medizin etabliert. Sie ermöglicht die nicht-invasive Validierung der Zielgenauigkeit, Wirksamkeit und Sicherheit von Wirkstoffen in lebenden Organismen und gewinnt zunehmend an Bedeutung in der pharmazeutischen Industrie. Die Forderung nach mehr Effizienz in der pharmazeutischen Forschung könnte durch neuartige Multitracer-Studien adressiert werden. Die Multi-Isotopen Akquisition mit Multi-Pinhole Kollimatoren ermöglicht die Validierung mehrerer Tracer in einem einzelnen Experiment und die Konsolidierung konsekutiver Bildgebungsstudien. Aufgrund physikalischer und technischer Limitationen ist die Bildqualität und Quantifizierbarkeit bei diesem Verfahren jedoch häufig reduziert. Um die Multi-Isotopen SPECT als zuverlässige und quantitative Bildgebungsmethode für den breiten Einsatz zu etablieren sind komplexe Korrekturverfahren erforderlich. Ziel der vorliegenden Arbeit war daher, die technischen Möglichkeiten und physikalischen Limitationen der Multi-Isotopen SPECT-Bildgebung in kleinen Labortieren systematisch zu untersuchen. Mithilfe von experimentellen Messungen und Monte Carlo Simulationen wurden spezifische Fehlerquellen identifiziert und Verfahren zur quantitativen Bildkorrektur entwickelt. Zudem wurde das Monte-Carlo Modell eines neuartigen SPECT/CT-Systems etabliert, um eine Plattform für die in-silico Optimierung von Bildgebungshardware, Aufnahmeprotokollen und Rekonstruktionsalgorithmen zu schaffen. Die Ergebnisse dieser Arbeit können die Bildqualität und Quantifizierbarkeit von SPECT in-vivo Daten für Multi-Isotopen Anwendungen verbessern. Sie führen beispielhaft durch den Prozess der Multi-Isotopen Protokolloptimierung und unterstützen die 3R-Initiative mit dem Ziel, experimentelle Tierversuche zu vermeiden (Replace), zu vermindern (Reduce) und zu verbessern (Refine)

ALBIRA: A small animal PET/SPECT/CT imaging system

Purpose: The authors have developed a trimodal PET/SPECT/CT scanner for small animal imaging. The gamma ray subsystems are based on monolithic crystals coupled to multianode photomultiplier tubes (MA-PMTs), while computed tomography (CT) comprises a commercially available microfocus x-ray tube and a CsI scintillator 2D pixelated flat panel x-ray detector. In this study the authors will report on the design and performance evaluation of the multimodal system. Methods: X-ray transmission measurements are performed based on cone-beam geometry. Individual projections were acquired by rotating the x-ray tube and the 2D flat panel detector, thus making possible a transaxial field of view (FOV) of roughly 80 mm in diameter and an axial FOV of 65 mm for the CT system. The single photon emission computed tomography (SPECT) component has a dual head detector geometry mounted on a rotating gantry. The distance between the SPECT module detectors can be varied in order to optimize specific user requirements, including variable FOV. The positron emission tomography (PET) system is made up of eight compact modules forming an octagon with an axial FOV of 40 mm and a transaxial FOV of 80 mm in diameter. The main CT image quality parameters (spatial resolution and uniformity) have been determined. In the case of the SPECT, the tomographic spatial resolution and system sensitivity have been evaluated with a99mTc solution using single-pinhole and multi-pinhole collimators. PET and SPECT images were reconstructed using three-dimensional (3D) maximum likelihood and ordered subset expectation maximization (MLEM and OSEM) algorithms developed by the authors, whereas the CT images were obtained using a 3D based FBP algorithm. Results: CT spatial resolution was 85μm while a uniformity of 2.7% was obtained for a water filled phantom at 45 kV. The SPECT spatial resolution was better than 0.8 mm measured with a Derenzo-like phantom for a FOV of 20 mm using a 1-mm pinhole aperture collimator. The full width at half-maximum PET radial spatial resolution at the center of the field of view was 1.55 mm. The SPECT system sensitivity for a FOV of 20 mm and 15% energy window was 700 cps/MBq (7.8 × 10−2%) using a multi-pinhole equipped with five apertures 1 mm in diameter, whereas the PET absolute sensitivity was 2% for a 350–650 keV energy window and a 5 ns timing window. Several animal images are also presented. Conclusions: The new small animal PET/SPECT/CT proposed here exhibits high performance, producing high-quality images suitable for studies with small animals. Monolithic design for PET and SPECT scintillator crystals reduces cost and complexity without significant performance degradation.This study was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grant PROMETEO 2008/114. The authors also thank Brennan Holt for checking and correcting the text.Sánchez Martínez, F.; Orero Palomares, A.; Soriano Asensi, A.; Correcher Salvador, C.; Conde Castellanos, PE.; González Martínez, AJ.; Hernández Hernández, L.... (2013). ALBIRA: A small animal PET/SPECT/CT imaging system. Medical Physics. 40(5):5190601-5190611. https://doi.org/10.1118/1.4800798S5190601519061140

Recent developments in time-of-flight PET

While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information

Co-planar PET/CT for small animal imaging

Proceeding of: 2005 IEEE Nuclear Science Symposium Conference Record, Puerto Rico, October 23 - 29, 2005A small animal PET/CT system based on a common rotating gantry is proposed. The PET detection subsystem is composed of two detector modules based on MLS arrays and four flat panel type PS PMT. The CT subsystem consists in a micro focus X ray tube and a semiconductor X ray detector. Space for opposed PET detectors and the CT scanner have been allocated on the same plane in such a way that the trans axial and axial centers are common for both systems. Shielding elements have been placed around the detectors to avoid cross modality contamination. The gantry can rotate 370 degrees to provide complete data sets for the CT image reconstruction algorithm that is based on the cone beam geometry. PET image reconstruction is implemented using FBP (2D and 3D) and OSEM. Sequential acquisition protocols minimize the scan duration, and CT information can be used to implement PET imaging corrections. The coplanar configuration of this system provides intrinsically co registered data sets, and it is not necessary to reposition the animal to perform any modality imaging, avoiding undesired animal or additional accessories movements. An additional advantage is the compactness of the system that saves space and allows a direct visual monitoring of the animal during the scanPart of this work is founded by the IM3 network (G03/185 Ministerio de Sanidad), with grants from the Ministerio de Educación y Ciencia, project TEC2004-07052-C02-01, and Ministerio de Industria, Turismo y Comercio project FIT-330101-2004-3. J.J. Vaquero has support from the “Ramón y Cajal” Program, Ministerio de Educación y Cienci

Approaches Toward Combining Positron Emission Tomography with Magnetic Resonance Imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) provide complementary information, and there has been a great deal of research effort to combine these two modalities. A major engineering hurdle is that photomultiplier tubes (PMT), used in conventional PET detectors, are sensitive to magnetic field. This thesis explores the design considerations of different ways of combining small animal PMT-based PET systems with MRI through experimentation, modelling and Monte Carlo simulation. A proof-of-principle hybrid PET and field-cycled MRI system was built and the first multimodality images are shown. A Siemens Inveon PET was exposed to magnetic fields of different strengths and the performance is characterized as a function of field magnitude. The results of this experiment established external magnetic field limits and design studies are shown for wide range of approaches to combining the PET system with various configurations of field-cycled MRI and superconducting MRI systems. A sophisticated Monte Carlo PET simulation workflow based on the GATE toolkit was developed to model the Siemens Inveon PET. Simulated PET data were converted to the raw Siemens list-mode format and were processed and reconstructed using the same processing chain as the data measured on the actual scanner. A general GATE add-on was developed to rapidly generate attenuation correction sinograms using the precise detector geometry and attenuation coefficients built into the emission simulation. Emission simulations and the attenuation correction add-on were validated against measured data. Simulations were performed to study the impact of radiofrequency coil components on PET image quality and to test the suitability of various MR-compatible materials for a dual-modality animal bed

Characterization of Dedicated PET Equipment with Non-Conventional Geometry

[ES] Desde su creación en la década de 1950, las imágenes tomográficas han resultado muy valiosas en el ámbito médico ayudando tanto en el diagnóstico como en el tratamiento de múltiples enfermedades. Dentro de la imagen molecular, los escáneres PET (Tomografía por Emisión de Positrones) generan información detallada de la interacción de los radio-trazadores con el tejido de estudio, pudiendo combinar dicha información con imagen anatómica de escáneres TC (Tomografía Computarizada) o RM (Resonancia Magnética). Con el fin de aumentar las prestaciones de estos equipos, como la sensibilidad y la resolución espacial, los PET de cuerpo completo recientemente aumentan su cobertura axial. Sin embargo, el precio de estos dispositivos se multiplica, dificultando su compra en muchos hospitales y centros de investigación. Como alternativa, los escáneres PET específicos de órganos manejan un menor número de detectores haciéndolos más económicos. El objetivo de este tipo de escáneres es mejorar el rendimiento de los dispositivos acercando los detectores al paciente lo máximo posible, optimizando su diseño para un órgano en específico. Otra ventaja es la posible portabilidad de los aparatos. En esta tesis introducimos dos posibles diseños de PET específicos orientados a distintos órganos y con diferente tecnología y geometría y además un escáner preclínico con una geometría novedosa. El primer escáner fue construido de un proyecto nacional llamado PROSPET, fue diseñado y optimizado para hacer imagen de la próstata, debido a la conocida elevada tasa de cáncer de próstata en hombres. El 17% de la población masculina sufrirá cáncer de próstata. El detector escogido para este diseño está compuesto por cristales centelladores monolíticos acoplados a una matriz de fotomultiplicadores de silicio. Inicialmente se pensó en crear un escáner compuesto por dos palas. Sin embargo, los resultados con pacientes no fueron satisfactorios debido a la falta de información angular y la ausencia de información temporal precisa en los detectores. Por tanto, se construyó una configuración de anillo con un diámetro reducido en comparación con escáneres de cuerpo completo. Se apreció un aumento en la sensibilidad y la resolución espacial, así como una buena calidad de imagen utilizando fantomas. El segundo escáner, llamado proyecto CardioPET, está orientado a visualizar el corazón cuando el paciente está sometido a condiciones de estrés farmacológico. Para este dispositivo se utilizó el diseño de dos palas, pero usando cristales pixelados, mejorando la resolución temporal, permitiendo implantar algoritmos de tiempo de vuelo. Se han montado y testeado dos palas tanto con simulaciones como experimentalmente con buenas prestaciones. Además, se procedió a registrar el movimiento de las fuentes de radiación con el fin de aplicar correcciones de movimiento con la ayuda de una cámara externa y unos marcadores ARUCO. Los algoritmos de corrección de movimiento fueron testeados, demostrando un buen funcionamiento. El último dispositivo fue diseñado para optimizar la configuración PET de anillo lo máximo posible. Para ello, se eliminaron los espaciados entre detectores en un escáner pequeño de animales, creando un único detector centellador de forma cilíndrica. Con esto se busca aumentar la sensibilidad, pues ya no se pierden interacciones en los huecos, y también la resolución espacial. Dos prototipos fueron testeados con simulaciones, y validados experimentalmente. El primero con caras de salida planas y el segundo totalmente cilíndrico. En ambos diseños se observaron efectos debidos a la curvatura del detector que necesariamente han de ser compensados con una calibración.[CA] Des de la seua creació en la dècada de 1950, les imatges tomogràfiques hi han resultat molt valuoses en àmbit mèdic ajudant tant en el diagnòstic com en el tractament de moltes malalties. Dins de la imatge molecular, els escàners PET (Tomografia per Emissió de Positrons) generen informació detallada de la interacció dels traçadors amb el teixit del pacient, podent combinar aquesta informació amb imatge anatòmica d'escàners TC (Tomografia Axial Automatitzada) o RM (Ressonancia Magnètica). Amb el fi d'augmentar les prestacions d’aquests equips, els PET de cos complet augmenten la seua cobertura axial, multiplicant el preu dels dispositius i dificultant la seua compra en hospitals i centres d’investigació. Com a alternativa, els escàners PET específics d'òrgans utilitzen un menor nombre de detectors resultant així un preu més econòmic. Un altre avantatge és la possible portabilitat dels aparells. En aquesta tesi abordem tres possibles dissenys de PET específics orientats a diferents òrgans i amb diferent tecnologia i geometria. El primer de tots, un projecte nacional denominat PROSPET, ha sigut dissenyat i optimitzat per a fer imatge de la pròstata, ja que és molt coneguda l'elevada taxa de càncer de pròstata en homes. El 17% de población masculina patirà càncer de pròstata. El detector escollit per a aquest disseny està format per cristals centellejadors monolítics acoblats a una matriu de fotomultiplicadors de silici. De primeres es va pensar a crear un escàner compost per dues pales, ja que permetria disposar els detectors molt a prop del pacient. El resultat no va ser molt satisfactori a causa de la falta d'informació angular i l'absència d'informació temporal precisa. Per tant, l'última iteració va consistir en una configuració d'anell amb un diàmetre reduït en comparació amb els escàners de cos complet. Es va observar una millora en la sensibilitat i la resolució espacial, així com una qualitat d'imatge acceptable. El segon dispositiu va ser dissenyat per a optimitzar la configuració d'anell el màxim possible. Per això es van llevar els espaiats entre detectors, creant un únic detector de forma cilíndrica. Amb aquest disseny es busca augmentar la sensibilitat, ja que no es perden interaccions en els espaiats, i també la resolució espacial. Dos prototips van ser testejats amb simulacions i validats experimentalment. El primer amb cares d'eixida planars i el segon totalment cilíndric. En els dos dissenys es va observar efectes deguts a la curvatura del detector que necessàriament ha de ser compensat amb una calibració. L’últim escàner, denominat projecte CardioPET, està orientat a visualitzar el cor durant el pacient quan és sotmés a condicions d'estrés farmacologic. escàner, denominat projecte CardioPET, està orientat a visualitzar el cor durant el pacient quan és sotmés a condicions d'estrés. Es va recuperar el disseny de les pales per aquest dispositiu, però utilitzant cristals pixelats, millorant la resolució temporal. Dues pales van ser muntades i testejades tant amb simulacions com experimentalment amb bones prestacions. A més, es va registrar el moviment de les fonts de radiació amb la fi d'aplicar correcció de moviment amb l'ajuda d'una càmera externa i uns marcadors ARUCO. Els algoritmes de correcció de moviment també van ser testejats, demostrant un bon funcionament. L'últim dispositiu va ser dissenyat per a optimitzar la configuració d'anell el màxim possible. Per això es van llevar els espaiats entre detectors, creant un únic detector de forma cilíndrica. Amb aquest disseny es busca augmentar la sensibilitat, ja que no es perden interaccions en els espaiats, i també la resolució espacial. Dos prototips van ser testejats amb simulacions i validats experimentalment. El primer amb cares d'eixida planars i el segon totalment cilíndric. En els dos dissenys es va observar efectes deguts a la curvatura del detector que necessàriament ha de ser compensat amb una calibració.[EN] Since their introduction in the 1950-decade, tomographic images have become very valuable in the medical field helping both in diagnostics and in a variety of illnesses treatment. In the molecular imaging field, Positron Emission Tomography (PET) provides accurate information of the radio-tracers interactions with the patient tissue. Moreover, it is possible to combine this information with anatomical images provided by CT (Computed Tomography) or MR (Magnetic Resonance) scanners. With the aim to improve PET systems performance, such as the spatial resolution and the sensitivity, whole body (WB) PET scanners with large axial coverage are recently proposed. However, the system cost increases and, thus, makes difficult their installation in many hospitals or research centers. Organ-dedicated PET scanners, as an alternative to such large systems, use a lower number of detectors, so their price is considerably more economical. The goal of this kind of systems is to boost PET performance by placing the detectors as close as possible to the patient, optimizing the design for a specific organ instead of a large volume. Other advantage of these scanners is their portability. In this thesis we have worked in the design and validation of two organ-dedicated PET scanners with different geometries and technologies, as well as in a novel pre-clinical PET. The first scanner was the result from a national project called PROSPET. A PET system was designed and optimized to image the prostate area. Notice there is a high incidence rate of prostate cancer in the male population. 17% of male population will suffer prostate cancer. For this scanner, the detector modules were composed by a monolithic LYSO scintillation block coupled to a photosensor array based on silicon photomultipliers (SiPM). The first design configuration was made by two panels. However, patient results were not satisfactory due to the lack of angular information and the poor detector time resolution. Therefore, it was rebuilt in a ring configuration with a reduced diameter in comparison with WB-PET scanners. A high sensitivity and spatial resolution were found, as well as a good image quality using phantoms. The second PET scanner, called CardioPET, also arose from a national grant, and it was implemented to visualize the heart area when the patient is under stress condition. The two panels geometry was also implemented for this system, but using pixelated crystals, therefore improving the detector time resolution and allowing to use time of flight (TOF) reconstruction algorithms. Two panels were mounted and tested with both simulation and experimental data with good results. Furthermore, the patient motion was registered applying movement correction techniques with the help of an external optical camera device and ARUCO markers. These algorithms were tested showing a good performance. The last device that we worked within this PhD thesis was designed to optimize the classical ring PET configuration as much as possible. To do so, the gaps between the detector modules in a small animal PET were eliminated by building a single detector with a cylindrical scintillator shape. The goal is to improve the sensitivity, given that there are no event losses in the gaps and to also boost the spatial resolution since there are not edges. Two prototypes were tested with simulations, and experimentally validated as well. The first of them was built with planar outer faces whereas the second was fully cylindrical. In both designs some effects originated from the detector curvature were observed and successfully corrected during the calibration.This thesis was supported by a FPI grant under 2017-08582 reference in the PhD program: “Programa de Doctorado en Tecnologías para la Salud y el Bienestar” belonging to the Polytechnic University of Valencia. The grant was supported by the “Consejo Superior de Investigaciones Científicas” together with the “Agencia Estatal de Investigación” and the “Fondo Social Europeo”.Cañizares Ledo, G. (2022). Characterization of Dedicated PET Equipment with Non-Conventional Geometry [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/184977TESI

Developments in PET-MRI for Radiotherapy Planning Applications

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance (QA) procedures for such corrections are lacking. Therefore, a dynamic phantom that is PET and MR compatible is required. Additionally, respiratory motion characterization is needed for conformal radiotherapy of lung. 4D-CT can provide 3D motion characterization but suffers from poor soft-tissue contrast. In this thesis, I examine these problems, and present solutions in the form of improved MR-hardware AC techniques, a PET/MRI/CT-compatible tumour respiratory motion phantom for QA measurements, and a retrospective 4D-PET-MRI technique to characterise respiratory motion. Chapter 2 presents two techniques to improve upon current AC methods that use a standard helical CT scan for MRI hardware in PET-MRI. One technique uses a dual-energy computed tomography (DECT) scan to construct virtual monoenergetic image volumes and the other uses a tomotherapy linear accelerator to create CT images at megavoltage energies (1.0 MV) of the RF coil. The DECT-based technique reduced artefacts in the images translating to improved μ-maps. The MVCT-based technique provided further improvements in artefact reduction, resulting in artefact free μ-maps. This led to more AC of the breast coil. In chapter 3, I present a PET-MR-CT motion phantom for QA of motion-correction protocols. This phantom is used to evaluate a clinically available real-time dynamic MR images and a respiratory-triggered PET-MRI protocol. The results show the protocol to perform well under motion conditions. Additionally, the phantom provided a good model for performing QA of respiratory-triggered PET-MRI. Chapter 4 presents a 4D-PET/MRI technique, using MR sequences and PET acquisition methods currently available on hybrid PET/MRI systems. This technique is validated using the motion phantom presented in chapter 3 with three motion profiles. I conclude that our 4D-PET-MRI technique provides information to characterise tumour respiratory motion while using a clinically available pulse sequence and PET acquisition method

Optical simulation study for high resolution monolithic detector design for TB-PET

Background The main limitations in positron emission tomography (PET) are the limited sensitivity and relatively poor spatial resolution. The administered radioactive dose and scan time could be reduced by increasing system sensitivity with a total-body (TB) PET design. The second limitation, spatial resolution, mainly originates from the specific design of the detectors that are implemented. In state-of-the-art scanners, the detectors consist of pixelated crystal arrays, where each individual crystal is isolated from its neighbors with reflector material. To obtain higher spatial resolution the crystals can be made narrower which inevitably leads to more inter-crystal scatter and larger dead space between the crystals. A monolithic detector design shows superior characteristics in (i) light collection efficiency (no gaps), (ii) timing, as it significantly reduces the number of reflections and therefore the path length of each scintillation photon and (iii) spatial resolution (including better depth-of-interaction (DOI)). The aim of this work is to develop a precise simulation model based on measured crystal data and use this powerful tool to find the limits in spatial resolution for a monolithic detector for the use in TB-PET. Materials and methods A detector (Fig. 1) based on a monolithic 50x50x16 mm3 lutetium-(yttrium) oxyorthosilicate (L(Y)SO) scintillation crystal coupled to an 8x8 array of 6x6mm2 silicon photomultipliers (SiPMs) is simulated with GATE. A recently implemented reflection model for scintillation light allows simulations based on measured surface data (1). The modeled surfaces include black painted rough finishing on the crystal sides (16x50mm2) and a specular reflector attached to a polished crystal top (50x50mm2). Maximum Likelihood estimation (MLE) is used for positioning the events. Therefore, calibration data is obtained by generating 3.000 photo-electric events at given calibration positions (Fig. 1). Compton scatter is not (yet) included. In a next step, the calibration data is organized in three layers based on the exact depth coordinate in the crystal (i.e. DOI assumed to be known). For evaluating the resolution, the full width at half maximum (FWHM) is estimated at the irradiated positions of Fig. 2 as a mean of all profiles in vertical and horizontal direction. Next, uniformity is evaluated by simulating 200k events from a flood source, placed in the calibrated area. Results For the irradiation pattern in Fig. 2 the resolution in terms of FWHM when applying MLE is: 0.86±0.13mm (Fig. 3a). Nevertheless, there are major artifacts also at non-irradiated positions. By positioning the events based on three DOI-based layers it can be seen that the events closest to the photodetector introduce the largest artifacts (Fig. 3b-d). The FWHM improves for Layer 1 and 2, to 0.69±0.04mm and 0.59±0.02mm, respectively. Layer 3 introduces major artifacts to the flood map, as events are positioned at completely different locations as the initial irradiation. A FWHM estimation is thus not useful. The uniformity (Fig. 4) degrades with proximity to the photodetector. The map in Fig. 4c shows that the positioning accuracy depends not only on DOI but also the position in the plane parallel to the photodetector array. Conclusions A simulation model for a monolithic PET detector with good characteristics for TB-PET systems was developed with GATE. A first estimate of the spatial resolution and uniformity was given, pointing out the importance of depth-dependent effects. Future studies will include several steps towards more realistic simulations e.g. surface measurements of our specific crystals for the optical surface model and inclusion of the Compton effect

The Performance of MLEM for Dynamic Imaging From Simulated Few-View, Multi-Pinhole SPECT

Stationary small-animal SPECT systems are being developed for rapid dynamic imaging from limited angular views. This work quantified, through simulations, the performance of Maximum Likelihood Expectation Maximization (MLEM) for reconstructing a time-activity curve (TAC) with uptake duration of a few seconds from a stationary, three-camera multi-pinhole SPECT system. The study also quantified the benefits of a heuristic method of initializing the reconstruction with a prior image reconstructed from a conventional number of views, for example from data acquired during the late-study portion of the dynamic TAC. We refer to MLEM reconstruction initialized by a prior-image initial guess (IG) as MLEMig. The effect of the prior-image initial guess on the depiction of contrast between two regions of a static phantom was quantified over a range of angular sampling schemes. A TAC was modeled from the experimentally measured uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in the rat lung. The resulting time series of simulated images was quantitatively analyzed with respect to the accuracy of the estimated exponential washin and washout parameters. In both static and dynamic phantom studies, the prior-image initial guess improved the spatial depiction of the phantom, for example improved definition of the cylinder boundaries and more accurate quantification of relative contrast between cylinders. For example in the dynamic study, there was ~ 50% error in relative contrast for MLEM reconstructions compared to ~ 25-30% error for MLEMig. In the static phantom study, the benefits of the initial guess decreased as the number of views increased. The prior-image initial guess introduced an additive offset in the reconstructed dynamic images, likely due to biases introduced by the prior image. MLEM initialized with a uniform initial guess yielded images that faithfully reproduced the time dependence of the simulated TAC; there were no s- atistically significant differences in the mean exponential washin/washout parameters estimated from MLEM reconstructions compared to the true values. Washout parameters estimated from MLEMig reconstructions did not differ significantly from the true values, however the estimated washin parameter differed significantly from the true value in some cases. Overall, MLEM reconstruction from few views and a uniform initial guess accurately quantified the time dependance of the TAC while introducing errors in the spatial depiction of the object. Initializing the reconstruction with a late-study initial guess improved spatial accuracy while decreasing temporal accuracy in some cases