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

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

[EN] Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostatespecific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4¿5 mm). Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organdedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.The work presented in this article has been partially funded by a research grant from the regional government of the Comunitat Valenciana (Spain), co-funded by the European Union ERDF funds (European Regional Development Fund) of the Comunitat Valenciana 2014-2020, with reference IDIFEDER/2018/032 (High-Performance Algorithms for the Modelling, Simulation and early Detection of diseases in Personalized Medicine). This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU Grant 603002 under the FP7 program and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant e and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad.Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Freire, M.; Lamprou, E.; Barrio, J.; Sánchez Martínez, F.; Benlloch Baviera, JM.... (2020). Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance. EJNMMI Physics. 7(1):1-17. https://doi.org/10.1186/s40658-020-00305-yS11771GLOBOCAN 2018. http://www.gco.iarc.fr/today/ datasources-methods. Accessed 26 Dec 2019.Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;2015:136–E359.Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63–89.Smith JA, et al. Transrectal ultrasound versus digital rectal examination for the staging of carcinoma of the prostate: results of a prospective multi-institutional trial. J Urology. 1997;157(3):902.Smeenge M, et al. Role of transrectal ultrasonography (TRUS) in focal therapy of prostate cancer: report from a consensus panel. BJU Int. 2012:110–942.Drost FJH, et al. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev. 2019;4:CD012663.European Association of Urology. https://uroweb.org/guideline/prostate-cancer . Accessed 26 Dec 2019.Segall G, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans. J Nucl Med. 2010;51:1813.Yamamoto Y, et al. Feasibility of tailored, selective and effective anticancer chemotherapy by direct injection of docetaxel-loaded immunoliposomes into Her2/neu positive gastric tumor xenografts. Int J Oncol. 2011;38(1):33.Chen L, et al. MR-guided focused ultrasound: enhancement of intratumoral uptake of [H]-docetaxel in vivo. Phys Med Biol. 2010;55(24):–7399.Osborne JR, et al. Prostate-specific membrane antigen-based imaging. Seminars and Original Investigations: Urologic Oncology; 2012.Gonzalez AJ, et al. Organ-dedicated molecular imaging systems. IEEE Trans. Rad. Plasma Med. Scie. 2018;2:388.Majewski S, Proffitt J. Dedicated mobile high resolution prostate PET imager with an insertable transrectal probe. US Patent. 2010;7:858–944.Weinberg IN, et al. Flexible geometries for hand-held PET and SPECT cameras. IEEE NSS-MIC Conference Record. 2002.Weinberg I. Dedicated apparatus and method for positron emission tomography of the prostate. US Patent. 2006;7:102–34.Gonzalez-Montoro A, et al. Performance study of a large monolithic LYSO PET detector with accurate photon DOI using retroreflector layers. IEEE Trans. Rad. Plasma Med. Scie. 2017;1:229.Gonzalez-Montoro A, et al. Detector block performance based on a monolithic LYSO crystal using a novel signal multiplexing method. Nucl Instrum Meth. 2018;912:372-77.Gonzalez-Montoro A, et al. Performance comparison of large-area SiPM arrays suitable for gamma ray detectors. Biomed Phys Eng Express. 2019;5:045013.Seimetz M, et al. Correction algorithms for signal reduction in insensitive areas of a small gamma camera. J Instrum. 2014;9(05):C05042.Freire M, et al. Calibration of gamma ray impacts in monolithic-based detectors using Voronoi diagrams. In IEEE Transactions on Radiation and Plasma Medical Sciences. 2019. https://doi.org/10.1109/TRPMS.2019.2947716 .Jan S, et al. GATE: a simulation toolkit for PET and SPECT. Phys Med Biol. 2004;49:4543–61.Merlin T, et al. CASToR: a generic data organization and processing code framework for multi-modal and multi-dimensional tomographic reconstruction. Phys Med Biol. 2018;63(18):5505.Jacobs F, et al. A fast algorithm to calculate the exact radiological path through a pixel or voxel space. J Comput Inf Technol. 1998;6(1).Gonzalez-Montoro A, et al. Novel method to measure the intrinsic spatial resolution in PET detectors based on monolithic crystals. Nucl. Instrum. Meth. A. 2019;920:39(9).Vicente E, et al. Normalization in 3D PET: dependence on the activity distribution of the source. IEEE Nuclear Science Symposium Conference Record. 2006:M06–379.Soriano A, et al. Attenuation correction without transmission scan for the MAMMI breast PET. Nucl Instrum Meth A. 2011;648:S75.Yushkevich PA, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;34(3):1116-28.Gonzalez AJ, et al. Initial results of the MINDView PET insert inside the 3T mMR. IEEE Trans Rad Plasma Med Scie. 2019;3:343.Suti S, et al. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med. 2007;48(3):471–80.Watson C, et al. NEMA NU 2 performance tests for scanners with intrinsic radioactivity. J Nucl Med. 2004;45:822.National Electrical Manufacturers Association. NEMA NU 4-2008. Performance measurements of small animal positron emission tomographs. 2008.Gonzalez AJ, et al. A PET design based on SiPM and monolithic LYSO crystals: performance evaluation. IEEE Trans Nucl Scie. 2016;63:2471.Barbosa FG. Clinical perspectives of PSMA PET/MRI for prostate cancer. Clinics. 2018;73(Suppl 1):e586s.Uprimny C, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44(6):941-49.Koerber SA, et al. 68Ga-PSMA-11 PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med. 2017;58(12):1943–8

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

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Monte Carlo simulations for system modeling in emission tomography

Non-invasive diagnostic imaging can be performed with different technologies:X-ray radiography, computed radiography, direct radiography, mammography,Computed Tomography (CT), UltraSound (US), and Magnetic Resonance Imaging (MRI), which all give anatomical information, and also with functional MRI (fMRI), optical imaging, thermography, planar isotope imaging,Single Photon Emission Tomography (SPECT), Positron Emission Tomography (PET), and gamma camera PET which return functional information.Recent devices combine two modalities on the same gantry in order to achieve hardware fusion of anatomical and functional images. Given the demographic aging in Western Europe, there exists a large interest in what is popularly referred to as a GPS-tool for cancer, i.e. a diagnostic tool for oncology that detects small malignant lesions in a very early stadium and that can be used for disease staging. Therefore research in nuclear medicine has a social support and bearing. In nuclear medicine examinations, a radiopharmaceutical is injected in the patient, marked with a radionuclide emitting one single photon with an energy of 100-200 keV in SPECT and a positron emitting radionuclide in PET. The emission of a positron finally results in two annihilation photons of 511 keV. Those photons are detected, mostly using a scintillation crystal that generates optical photons which travel through a light guide before reaching the PhotoMultiplierTubes (PMTs). Those PMTs convert the optical photons to electrons, which are in their turn used to generate a position and energy encoding signal. In PET there is an electronic collimation to acquire directional information while this information is obtained by applying a lead collimator in SPECT. The acquired data is afterwards reconstructed to result in a threedimensional radioactive tracer distribution within the patient. Optimization,evaluation and (re)design of all elements in this detection chain is mostly done using simulations. Given the possibility of modeling different physical processes, the Monte Carlo method has also been applied in nuclear medicine to a wide range of problems that could not be addressed by experimental or analytical approaches

System parameters and performance specifications for the application of Diffraction Enhanced Imaging and Multiple Image Radiography to breast imaging

The Diffraction Enhanced Imaging (DEI) method is a novel x-ray imaging technique that dramatically extends the capability of conventional x-ray imaging. X-ray imaging has traditionally been dependent on x-ray absorption to generate contrast, and is the physical mechanism of contrast in planar x-ray imaging and computed tomography. DEI utilizes the Bragg peak of perfect crystal diffraction to convert angular changes into intensity changes, providing a large change in intensity for a small change in angle. The use of a silicon analyzer crystal in the path of the x-ray beam generates two additional forms of image contrast, refraction and extinction. Objects that have very little absorption contrast may have considerable refraction and extinction contrast, this improving visualization and extending the utility of x-ray imaging. An area of medicine where this technique could have a dramatic impact is in breast imaging, where the key diagnostic structures often have low absorption contrast, especially in the early stages of disease. In order to develop a DEI clinical prototype imaging system, a systematic assessment of the engineering parameters for the breast imaging application must be determined. This body of work investigates the primary imaging parameters of DEI (x-ray beam energy, crystal reflections, angular sampling) and demonstrates how the unique properties of DEI can be capitalized upon to address the engineering limitations of flux, dramatically reducing the dose required for imaging. The results from this analysis are used to describe a plausible design for a non-synchrotron based DEI breast imaging system

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