The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Real-Time Digital Timing in Positron Emission Tomography

Positron emission tomography (PET) requires accurate timing of scintillation events to properly discriminate between coincident and noncoincident pairs. The traditional solution to timing is based on custom application specific integrated circuits (ASIC) designs, whose cost may not be justified in the design of experimental small animal PET scanners. The new generation of PET scanners introduces the idea of continuous sampling of the detected scintillation pulse, replacing event-triggered acquisition front-ends. This approach enables new options to the timing procedure based on digital processing of the sampled pulse signal. This work proposes a time stamping algorithm based on the optically matched filter and compares the potential performance benefits of this approach versus other FIR-based timing algorithms, some of which have been already implemented by different authors. Results show that the coincidence timing resolution may be as low as 1.5 ns without the need of expensive high-speed converters when the proper signal processing is appliedIEEE Nuclear and Plasma Sciences SocietyPublicad

Digital timing in positron emission tomography

Proceeding of: 2006 IEEE Nuclear Science Symposium Conference Record, San Diego, CA, Oct. 29 - Nov. 1, 2006Positron emission tomography (PET) requires accurate timing of events in order to properly discriminate between coincident and non-coincident events. The traditional solution to timing is based on custom ASIC designs, whose cost may not be justified in the design of an experimental small animal PET scanner. The new generation of PET scanners introduces the idea of continuous sampling of the detected scintillation pulse, in substitution of the event triggered acquisition systems. This approach enables new options to timing based on digital processing of the sampled pulse signal. This work proposes a time stamping algorithm based on the optically matched filter and compares the potential performance benefits of this approach versus other FIR filter designs, some of which have been already implemented by different authors. Results show that time resolution of the timestamp may be as 1 ns without the need of expensive high-speed converters when the proper processing is applied.This work has been partially funded by the Spanish Ministry of Culture and Science through the FPU grant program as well as projects TEC2004-07052-C02-02 and PI052204.

Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners

Tesis por compendio[ES] La Tomografía por Emisión de Positrones (PET) es una de las técnicas más importantes en la medicina de diagnóstico actual y la más representativa en el campo de la Imagen Molecular. Esta modalidad de imagen es capaz de producir información funcional única, que permite la visualización en detalle, cuantificación y conocimiento de una variedad de enfermedades y patologías. Áreas como la oncología, neurología o la cardiología, entre otras, se han beneficiado en gran medida de esta técnica. A pesar de que un elevado número de avances han ocurrido durante el desarrollo del PET, existen otros que son de gran interés para futuras investigaciones. Uno de los principales pilares actualmente en PET, tanto en investigación como en desarrollo, es la obtención de la información del tiempo de vuelo (TOF) de los rayos gamma detectados. Cuando esto ocurre, aumenta la sensibilidad efectiva del PET, mejorando la calidad señal-ruido de las imágenes. Sin embargo, la obtención precisa de la marca temporal de los rayos gamma es un reto que requiere, además de técnicas y métodos específicos, compromisos entre coste y rendimiento. Una de las características que siempre se ve afectada es la resolución espacial. Como discutiremos, la resolución espacial está directamente relacionada con el tipo de centellador y, por lo tanto, con el coste del sistema y su complejidad. En esta tesis, motivada por los conocidos beneficios en imagen clínica de una medida precisa del tiempo y de la posición de los rayos gamma, proponemos configuraciones de detectores TOF- PET novedosos capaces de proveer de ambas características. Sugerimos el uso de lo que se conoce como métodos de "light-sharing", tanto basado en cristales monolíticos como pixelados de tamaño diferente al del fotosensor. Estas propuestas hacen que la resolución espacial sea muy alta. Sin embargo, sus capacidades temporales han sido muy poco abordadas hasta ahora. En esta tesis, a través de varios artículos revisados, pretendemos mostrar los retos encontrados en esta dirección, proponer determinadas configuraciones y, además, indagar en los límites temporales de éstas. Hemos puesto un gran énfasis en estudiar y analizar las distribuciones de la luz centellante, así como su impacto en la determinación temporal. Hasta nuestro conocimiento, este es el primer trabajo en el que se estudia la relación de la determinación temporal y la distribución de luz de centelleo, en particular usando SiPM analógicos y ASICs. Esperamos que esta tesis motive y permita otros muchos trabajos orientados en nuevos diseños, útiles para instrumentación PET, así como referencia para otros trabajos. Esta tesis esta organizada como se describe a continuación. Hay una introducción compuesta por tres capítulos donde se resumen los conocimientos sobre imagen PET, y especialmente aquellos relacionados con la técnica TOF-PET. Algunos trabajos recientes, pero aún no publicados se muestran también, con el objetivo de corroborar ciertas ideas. En la segunda parte se incluyen las cuatro contribuciones que el candidato sugiere para el compendio de artículos.[CA] La Tomografia per Emissió de Positrons (PET) és una de les tècniques més importants en la medicina de diagnòstic actual i la més representativa en el camp de la Imatge Molecular. Esta modalitat d'imatge és capaç de produir informació funcional única, que permet la visualització en detall, quantificació i coneixement d'una varietat de malalties i patologies. Àrees com l'oncologia, neurologia o la cardiologia, entre altres, s'han beneficiat en gran manera d'aquesta tècnica. Tot i que un elevat nombre d'avanços han ocorregut durant el desenvolupament del PET, hi ha altres que són de gran interés per a futures investigacions. Un dels principals pilars actuals en PET, tant en investigació com en desenvolupament, és l'obtenció de la informació del temps de vol (TOF en anglès) dels raigs gamma detectats. Quan açò ocorre, augmenta la sensibilitat efectiva del PET, millorant la qualitat senyal-soroll de les imatges. No obstant això, l'obtenció precisa de la marca temporal dels raigs gamma és un repte que requerix, a més de tècniques i mètodes específics, compromisos entre cost i rendiment. Una de les característiques que sempre es veu afectada és la resolució espacial. Com discutirem, la resolució espacial està directament relacionada amb el tipus de centellador, i per tant, amb el cost del sistema i la seua complexitat. En aquesta tesi, motivada pels coneguts beneficis en imatge clínica d'una mesura precisa del temps i de la posició dels raigs gamma, proposem nouves configuracions de detectors TOF-PET capaços de proveir d'ambduess característiques. Suggerim l'ús del que es coneix com a mètodes de "light-sharing", tant basat en cristalls monolítics com pixelats de diferent tamany del fotosensor. Aquestes propostes fan que la resolució espacial siga molt alta. No obstant això, les seues capacitats temporals han sigut molt poc abordades fins ara. En aquesta tesi, a través de diversos articles revisats, pretenem mostrar els reptes trobats en aquesta direcció, proposar determinades configuracions i, a més, indagar en els límits temporals d'aquestes. Hem posat un gran èmfasi a estudiar i analitzar les distribucions de la llum centellejant, així com el seu impacte en la determinació temporal. Fins al nostre coneixement, aquest és el primer treball en què s'estudia la relació de la determinació temporal i la distribució de llum de centelleig, en particular utilitzant SiPM analògics i ASICs. Esperem que aquesta tesi motive i permeta molts altres treballs orientats en nous dissenys, útils per a instrumentació PET, així com referència per a altres treballs. Aquesta tesi esta organitzada com es descriu a continuació. Hi ha una introducció composta per tres capítols on es resumeixen els coneixements sobre imatge PET i, especialmente, aquells relacionats amb la tècnica TOF-PET. Alguns treballs recents, però encara no publicats es mostren també, amb l'objectiu de corroborar certes idees. La segona part de la tesi conté els quatre articles revisats que el candidat suggereix.[EN] Positron Emission Tomography (PET) is one of the greatest tools of modern diagnostic medicine and the most representative in the field of molecular imaging. This imaging modality, is capable of providing a unique type of functional information which permits a deep visualization, quantification and understanding of a variety of diseases and pathologies. Areas like oncology, neurology, or cardiology, among others, have been well benefited by this technique. Although numerous important advances have already been achieved in PET, some other individual aspects still seem to have a great potential for further investigation. One of the main trends in modern PET research and development, is based in the extrapolation of the Time- Of-Flight (TOF) information from the gamma-ray detectors. In such case, an increase in the effective sensitivity of PET is accomplished, resulting in an improved image signal-to-noise ratio. However, the direction towards a precise decoding of the photons time arrival is a challenging task that requires, besides specific approaches and techniques, tradeoffs between cost and performance. A performance characteristic very habitually compromised in TOF-PET detector configurations is the spatial resolution. As it will be discussed, this feature is directly related to the scintillation materials and types, and consequently, with system cost and complexity. In this thesis, motivated by the well-known benefits in clinical imaging of a precise time and spatial resolution, we propose novel TOF-PET detector configurations capable of inferring both characteristics. Our suggestions are based in light sharing approaches, either using monolithic detectors or crystal arrays with different pixel-to-photosensor sizes. These approaches, make it possible to reach a precise impact position determination. However, their TOF capabilities have not yet been explored in depth. In the present thesis, through a series of peer-reviewed publications we attempt to demonstrate the challenges encountered in these kinds of configurations, propose specific approaches improving their performance and eventually reveal their limits in terms of timing. High emphasis is given in analyzing and studying the scintillation light distributions and their impact to the timing determination. To the best of our knowledge, this is one of the first works in which such detailed study of the relation between light distribution and timing capabilities is carried out, especially when using analog SiPMs and ASICs. Hopefully, this thesis will motivate and enable many other novel design concepts, useful in PET instrumentation as well as it will serve as a helpful reference for similar attempts. The present PhD thesis is organized as follows. There is an introduction part composed by three detailed sections. We attempt to summarize here some of the knowledge related to PET imaging and especially with the technique of TOF-PET. Some very recent but still unpublished results are also presented and included in this part, aiming to support statements and theories. The second part of this thesis lists the four peer-reviewed papers that the candidate is including.This project has 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 Spanish Ministerio de Economía, Industria y Competitividad under Grants No. FIS2014-62341-EXP and TEC2016-79884-C2-1-R. Efthymios Lamprou has also been supported by Generalitat Valenciana under grant agreement GRISOLIAP-2018-026.Lamprou, E. (2021). Development and Performance Evaluation of High Resolution TOF-PET Detectors Suitable for Novel PET Scanners [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/162991TESISCompendi

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society

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

Functional Imaging of Autonomic Regulation: Methods and Key Findings.

Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function

Simulación de rango del positrón y emisiones gamma adicionales en PET

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Física Atómica, Molecular y Nuclear, leída el 03-04-2014Depto. de Estructura de la Materia, Física Térmica y ElectrónicaFac. de Ciencias FísicasTRUEunpu