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<p>Dual modality imaging systems such as SPECT/CT have become commonplace in medical imaging as it aids in diagnosing diseases by combining anatomical images with functional images. We are interested in developing a dual modality imaging system combining SPECT and MR imaging because MR does not require any ionizing radiation to image anatomical structures and it is known to have superior soft tissue contrast to CT. However, one of the fundamental challenges in developing a SPECT/MR system is that traditional gamma cameras with photomultiplier tubes are not compatible within magnetic fields. New development in solid state detectors has led to the silicon photomultiplier (SiPM), which is insensitive to magnetic fields.</p> <p>We have developed a small area gamma camera with a tileable 4x4 array of SiPM pixels coupled with a CsI(Tl) scintillation crystal. A number of simulated gamma camera geometries were performed using both pixelated and monolithic scintillation crystals. Several event positioning algorithms were also investigated as an alternative to conventional Anger logic positioning. Simulations have shown that we can adequately resolve intrinsic spatial resolution down to 1mm, even in the presence of noise. Based on the results of these simulations, we have built a prototype SiPM system comprised of 16 detection channels coupled to discrete crystals. A charge sensitive preamplifier, pulse height detection circuit and a digital acquisition system make up our pulse processing components in our gamma camera system. With this system, we can adequately distinguish each crystal element in the array and have obtained an energy resolution of 30±1 (FWHM) with Tc-99m (140keV). In the presence of a magnetic field, we have seen no spatial distortion of the resultant image and have obtained an energy resolution of 31±3.</p> / Master of Science (MSc)

<p>As the number of transistors that are integrated onto a silicon die continues to in- crease, the compute power is becoming a commodity. This has enabled a whole host of new applications that rely on high-throughput computations. Recently, the need for faster and cost-effective applications in form-factor constrained environments has driven an interest in on-chip acceleration of algorithms based on Monte Carlo simula- tions. Though Field Programmable Gate Arrays (FPGAs), with hundreds of on-chip arithmetic units, show significant promise for accelerating these embarrassingly paral- lel simulations, a challenge exists in sharing access to simulation data amongst many concurrent experiments. This thesis presents a compute architecture for accelerating Monte Carlo simulations based on the Network-on-Chip (NoC) paradigm for on-chip communication. We demonstrate through the complete implementation of a Monte Carlo-based image reconstruction algorithm for Single-Photon Emission Computed Tomography (SPECT) imaging that this complex problem can be accelerated by two orders of magnitude on even a modestly-sized FPGA over a 2GHz Intel Core 2 Duo Processor. Futhermore, we have created a framework for further increasing paral- lelism by scaling our architecture across multiple compute devices and by extending our original design to a multi-FPGA system nearly linear increase in acceleration with logic resources was achieved.</p> / Master of Applied Science (MASc)

[EN] Idiopathic pulmonary fibrosis (IPF) is the pulmonary disease with higher incidence and worse prognosis. Recent evidence suggests that cucurbitaceae, selective inhibitors of the JAK2/STAT3 pathway, may improve the pathogenesis of IPF, as anti-inflammatory and antioxidative properties have been confirmed in other diseases. However the role in IPF is unknown. Two pharmacological models were investigated in the present study. In the preventive model, Wistar rats were instilled intratracheally with a single dose of bleomycin (BLM)(3.75 U/kg; n=12) to induce lung injury. CuI (20mg/kg/day; n=6) or CuI vehicle (control and IPF group) was administered intraperitoneally daily for 21 days. The therapeutic model was exactly the same starting CuI administration on day 7 until day 21. Animal evolution together with the ventilation-perfusion ratio was controlled through CT/SPECT imaging. Cellular count and characterization was performed in broncoalveolar lavage (BAL) together with the total protein content and the IL-6 and IL-13 concentration in BAL and lung tissue. Hematoxilin-eosin and masson trichrome stains allowed the study of the lung's tissue histology. TGF-ß1, CTGF, COL1A and ET-1 gene and protein expression were both measured by real time PCR and WB as pulmonary vascular remodeling markers. P-STAT3, P-SMAD3 and P-JAK2 proteins were determined by protein and immunohistochemistry quantification. Finally, JAK2 and STAT3 expression and distribution was studied in lung tissue of fibrotic patients with pulmonary hypertension. CT/SPECT quantification showed reduction of the fibrotic areas in the CuI treated group by reestablishing the air space in the lungs back to day 0 levels for the preventive and the therapeutic model. Furthermore, ventilation/perfusion correlation was restored in the therapeutic model after administrating CuI during 14 days. Hematoxilin-eosine stains demonstrated how the group treated pharmacologically presented an improvement in the lung tissue architecture, reversing vascular remodeling and right heart hypertrophy. Masson trichrome stain revealed a reduction of the collagen deposits. Ashcroft score, used to determine the severity of pulmonary fibrosis, was measured and diminished significantly in the CuI treated group. The results showed a gene and protein overexpression of TGF-ß1, CTGF, COL1A and ET-1 in BLM relative to Control rats. This was counteracted with CuI treatment which reduced the expression back to control. In terms of immunohistochemistry, the results demonstrated a decrease in the COL1A deposits in the treated group versus the absence of treatment group. Protein and immunohistochemistry analysis of JAK2, STAT3 and SMAD3 demonstrated an overexpression in bleomycin rats while the protein expression was inhibited in the CuI treated group. In accordance to the results obtained, the immunohistochemistry analysis of the lung parenchyma in patients with pulmonary hypertension related to pulmonary fibrosis showed and overexpression of the phosphorylated forms of JAK2 and STAT3, lacking its expression in healthy lung tissue. The preventive and therapeutic administration of JAK2/STAT3 inhibitor can be a potential treatment for pulmonary fibrosis, as it improves the parameters related to the disease. / [ES] La fibrosis pulmonar idiopática (FPI) es la enfermedad pulmonar con mayor incidencia y peor pronóstico. Estudios recientes sugieren que la familia de las cucurbitaceae, inhibidores selectivos de la ruta JAK2/STAT3, pueden mejorar la patogénesis de la enfermedad, al haberse confirmado sus propiedades antinflamatorias y antioxidantes en otras enfermedades. Sin embargo se desconoce su papel en FPI. En el presente trabajo se estudiaron dos modelos farmacológicos. En el modelo preventivo las ratas Wistar fueron instiladas con una dosis única de bleomicina intratraqueal (BLM)(3.75 U/kg; n=12) para inducir las lesión pulmonar. Durante 21 días se administró CuI (20mg/kg/día; n=6) o vehículo de CuI (control y grupo FPI) por vía intraperitoneal. El modelo curativo se diferencia del preventivo en el comienzo de la administración farmacológica a los 7 días de inducir la enfermedad. El seguimiento de la evolución animal y el ratio de ventilación-perfusión se realizó mediante las técnicas de imagen TC/SPECT. Se realizó el recuento y caracterización de las células totales extravasadas en lavado broncoalveolar (LBA) así como el contenido de proteína total y la concentración de IL- 6 e IL-13 en LBA y tejido pulmonar. Las tinciones de hematoxilina-eosina y masson tricrómico permitieron el estudio de la histología del tejido pulmonar. Se determinó la expresión génica y proteica de TGF-ß1, CTGF, COL1A y ET-1 mediante las técnicas de real time PCR y WB como marcadores de remodelado vascular. Las proteínas P-STAT3, P-SMAD3 y P-JAK2, fueron determinadas mediante cuantificación proteica e inmunohistoquimia. Por último se estudió la expresión y distribución de JAK2 y STAT3 en tejido de pacientes con fibrosis pulmonar e hipertensión pulmonar. La cuantificación de las imágenes TC/SPECT mostraron una reducción de las áreas fibróticas en el grupo tratado con CuI. El tratamiento farmacológico permitió el restablecimiento del espacio aéreo pulmonar hasta valores control en ambos modelos estudiados. El grupo con tratamiento farmacológico restauró el ratio de ventilación/perfusión tras administrar CuI durante 14 días. Las tinciones de hematoxilina eosina revelaron como el grupo animal tratado farmacológicamente presenta una mejora de la histología pulmonar, revirtiendo el remodelado vascular y la hipertrofia del ventrículo derecho. La tinción de masson tricrómico mostró una disminución de los depósitos de colágeno. Se determinó el valor de Ashcroft, evaluador del grado de fibrosis pulmonar, que descendió significativamente en el grupo tratado con CuI. Los resultados presentan una sobrexpresión génica y proteica de TGF-ß1, CTGF, COL1A y ET-1 en los grupos de bleomicina frente a las ratas control. Dicha condición fue revertida mediante el tratamiento con CuI que restableció los valores a niveles control. Los análisis proteicos e inmunohistoquíimicos de JAK2, STAT3 y SMAD3 revelaron una sobreexpresión en las ratas con bleomicina mientras que la expresión proteica fue inhibida en el grupo tratado con CuI. En consonancia con los resultados obtenidos, el análisis inmunohistoquímico del parénquima pulmonar de pacientes con FPI e HP asociada muestran una sobreeexpresión de las formas fosforiladas de JAK2 y STAT3 frente a la ausencia de expresión en tejido pulmonar sano. La administración curativa y preventiva de un inhibidor de la ruta JAK2/STAT3 puede ser un potencial tratamiento para la fibrosis pulmonar, ya que mejora parámetros indicativos de la patología. / [CA] La fibrosi pulmonar idiopàtica (FPI) és la enfermetat pulmonar amb major incidència i pitjor pronostic. Estudis recents suggereixen que la família de les cucurbitàcies, Inhibidors selectius de la ruta JAK2 / STAT3, poden millorar la patogènesi de la malaltia, en haver-se confirmat les seues propietats antiinflamatòries i antioxidants En altres patologies. No obstant això es desconeix el seu paper en FPI. En el present treball es van estudiar 2 models farmacològics. En el model preventiu les rates Wistar foren instilades amb una dosi única de bleomicina intratraqueal (BLM) (3,75 U / kg; n = 12) per a induir les lesions pulmonars. Durant 21 dies es va administrar CuI (20 mg / kg / dia, n = 6) o Vehicle de CuI (control i grup FPI) per vía intraperitoneal. El model curatiu es diferència del preventiu en el començament de l'administració farmacológica als 7 dies d'induir l'enfermetat. El seguiment de l'evoluciò dels animals i el ratio de Ventilació-perfusió es va realitzar mitjançant tècniques d'imatge TC/SPECT. Es realitzà el recompte i caracterització de les cèl·lules totals extravasades en el llavat broncoalveolar (LBA). Així com el contingut de proteina total i la concentració d'IL-6 i IL-13 en LBA i teixit pulmonar. Les tincions d'hematoxilina-eosina i tricròmic de Masson van permetre l'estudi de la histologia del teixit pulmonar. Es va determinar l'expressió gènica i proteica de TGF-ß1, CTGF, COL1A i Et-1 mitjançant tècniques de PCR en temps real i WB com marcadors de remodelat vascular. Les proteïnes P-STAT3, P-SMAD3 i P-JAK2, varen ser determinades mitjançant quantificació proteica i inmunohistoquimia. Per últim se estudià l'expressió i distribució de JAK2 i STAT3 en teixit de pacients amb fibrosi pulmonar e hipertensió pulmonar. La quantificació de les imatges TC/SPECT mostraren una reducció de les àrees fibrótiques en el grup tractat amb CuI. El tractament farmacològic permet el restabliment de l'espai aeri pulmonar fins valors de control en els dos models estudiats. El grup amb tractament farmacològic va restaurar el ratio de ventilació/perfusió tras administrar Cul durant 14 dies. Les tincions d'hematoxilina eosina van revelar com el grup animal tractat farmacològicament presenta una Millora de la histologia pulmonar, revertint el remodelat vascular i la hipertròfia del ventricle dret. La tinció de tricròmic de Masson va mostrar una disminució dels dipòsits de col·lagen. Es va determinar el valor d'Ashcroft, avaluador del grau de fibrosi pulmonar, que va baixar significativament a el grup tractat amb CuI. Els resultats presenten una sobreexpressió gènica i proteica de TGF-ß1, CTGF, COL1A i Et-1 en els grups de bleomicina en comparacióa les rates control. Aquesta condició va ser revertida mitjançant el tractament amb CuI que va restablir els valors fins a nivel dels control. A nivell immunohistoquímic els resultats mostren una disminució dels dipòsits de COL1A en el grup tractat comparativament al grup sense tractament. Els anàlisi proteics i inmunohistoquíimics de JAK2, STAT3 i SMAD3 van revelar una sobreexpressió en les rates amb bleomicina mentre que l'expressió proteica va ser inhibida en el grup tractat amb CuI. D'acord amb els resultats obtinguts, l'anàlisi immunohistoquímic del parènquima pulmonar de pacients amb FPI i HP associada mostren sobreeexpresió de les formes fosforilades de JAK2 i STAT3 davant l'absència d'expressió en teixit pulmonar sa. La administració curativa i preventiva d'un inhibidor de la ruta JAK2 / STAT3 pot ser un potencial tractament per la fibrosi pulmonar, ja que millora paràmetres indicatius de la patologia. / Hernández Ribes, G. (2016). ESTUDIO DE LA RUTA CELULAR JAK2/STAT3 COMO POTENCIAL INHIBIDOR EN EL MODELO DE FIBROSIS PULMONAR [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/64087

Traditionally, medical imaging techniques such as PET (positron emission tomography) and SPECT (single-photon emission computed tomography) have relied on mechanical collimators to detect the sources of photons. This limits the image's resolution and field of view. To improve upon this, Compton cameras have emerged as a promising alternative. The principle is to measure the angle of a photon scattered in the detector, which indicates the likely sources in the form of a cone culminating in the position of the interaction. The cones from multiple events may be superimposed in order to generate an image. The object of this work is to use list-mode likelihood methods to better reconstruct the source image from the data recorded by a simulated Compton camera in the case of a solid detector volume with good spatial- and energy resolution.  The results demonstrate an improvement of image quality for reconstructions of single point source and multiple extended sources. In addition, the results indicate that our used algorithm converges for point sources. The minimum number of measured events for accurate reconstruction for different source distributions remains to be determined, and the algorithm's ability to resolve closely adjacent sources should be investigated more.

Ce texte de mémoire est accompagné du webdocumentaire interactif : De la chaise à la mer, disponible à l'adresse http://www.delachaisealamer.net. / Ce mémoire de recherche et création étudie le rôle du cinéaste dans la mise en forme de documentaires interactifs diffusés sur le Web. L’auteur se réfère d’abord à ses propres documentaires conventionnels afin d’en définir le principal objectif énonciateur. Puis, il observe les nouvelles positions de spectature favorisées par les dispositifs actuels de distribution médiatique pour comprendre la forme à donner à l’œuvre interactive qu’il est à produire et juger de la possibilité d’y inscrire ses intentions de communication habituelles. L'auteur se réfère par la suite aux documentaires interactifs auxquels il a participé dans les années 1990 et détermine les dispositifs d’interaction permettant une présence active du spectateur. Finalement, l’auteur explique les étapes de production de son webdocumentaire et souligne les éléments de recherche qui ont guidé sa création. L’auteur conclut avec quelques réflexions concernant le rapport existant entre le créateur d’une œuvre documentaire interactive et le spect-acteur multitâche actuel. / This research-creation dissertation studies the filmmaker’s role in the production of interactive web documentaries. First, the author recalls conventional documentaries he directed in order to indentify their primary discursive objectives. Then, he examines the new spectatorship being defined by current media delivery devices to better understand the shape to be given to the interactive work he’s producing and assess its ability in carrying his usual communication objectives. Subsequently, the author refers to interactive documentaries in which he participated in the 1990s and points out specific interactive devices showing to be efficient in taking into account the active presence of the viewer. Finally, the author describes the making of his web documentary and highlights aspects of his research that guided its production. The author concludes with some remarks regarding his creative process and the relationship existing between the filmmaker creator of an interactive documentary and today’s new multitask spect-actor.

Tomografia computadorizada por emissão de fóton único (SPECT) é uma modalidade da medicina nuclear baseada na medida da distribuição espacial de um radionuclídeo. Esta técnica é amplamente utilizada em cardiologia para avaliar problemas de perfusão miocárdica, relacionados ao fluxo sanguíneo nas artérias coronárias. As imagens SPECT proporcionam melhor separação das regiões do miocárdio e facilitam a localização e a definição dos defeitos de perfusão. Um dos grandes desafios em estudos SPECT é a eficiente apresentação da informação, uma vez que um único estudo pode gerar imagens de centenas de cortes a serem analisados. Para resolver este problema, são utilizados mapas polares (também conhecidos como gráficos Bulls Eye). Mapas polares são construídos a partir de cortes tomográficos do ventrículo esquerdo e apresentam as informações dos exames de forma sumarizada, em uma imagem bidimensional. Essa dissertação apresenta um método para segmentação do ventrículo esquerdo em estudos SPECT do miocárdio e a construção de mapas polares. A segmentação do ventrículo esquerdo é realizada para facilitar o processo de geração automática de mapas polares. O método desenvolvido utiliza a transformada watershed, no contexto do paradigma de Beucher-Meyer. Para visualização dos resultados, foi desenvolvida uma aplicação, chamada Medical Image Visualizer (MIV). O MIV será disponibilizado como projeto Open Source, podendo ser livremente utilizado e/ou modificado pela comunidade de usuários, desenvolvedores e pesquisadores. / Single photon emission computed tomography (SPECT) is a nuclear medicine tomographic imaging technique based on the measurement of spatial distribution of a radionuclide. This technique is widely used in cardiology to assess myocardial perfusion problems related to blood flow in coronary arteries. SPECT images provide better separation of regions of the myocardium and facilitate the location and definition of perfusion defects. One of the major challenges in SPECT studies is the efficient presentation of information, since a single study can generate hundreds of images of slices to be analyzed. To address this issue, polar maps (also known as Bulls Eye display) are used. Polar maps are built from slices of the left ventricle and provide summarized information of exams in a two dimensional image. This dissertation presents a method for the segmentation of the left ventricle in myocardial SPECT studies and the construction of polar maps. The segmentation of the left ventricle is performed to facilitate the process of automatic generation of polar maps. The method uses the watershed transform, in the context of the Beucher-Meyer paradigm. To display the results, it was developed an application called Medical Image Visualizer (MIV). MIV will be available as an Open Source project and the communities of users, developers and researchers will be able to freely use and/or modify the application.

L’objectif principal de ce travail est de caractériser par une approche multimodale d’imagerie les bases neurales structurales et fonctionnelles qui sous-tendent les troubles cognitifs et la QV dans la schizophrénie. L’objectif secondaire est de tester la valeur prédictive des troubles cognitifs et de la QV pour l’évolution et le fonctionnement dans la schizophrénie.Nous avons d’abord exploré les profils d’activation cérébrale au cours d’une tâche de mémoire de travail entre des patients qui ont une courte durée d’évolution de la maladie et ceux qui ont une longue durée d’évolution de la maladie. Nous avons retrouvé une hyper activation de certaines régions cérébrales chez les patients avec un longue durée d’évolution de la maladie comparativement aux patients avec une courte durée d’évolution. Nous avons ensuite étudié les bases neurales structurales de la QV. Nous avons mis en évidence qu’une QV altérée était associée à des changements plus importants de la microstructure cérébrale dans des régions altérées par le processus pathologique de la schizophrénie. Nous avons enfin étudié les réseaux cérébraux fonctionnels qui sous-tendent la QV. Nous rapportons que des régions cérébrales impliquées dans la prise de décision, dans le traitement des émotions et dans les cognitions sociales sont liées aux dimensions de la QV.D’une part nos travaux suggèrent qu’une réorganisation fonctionnelle dans le réseau cérébral de la mémoire de travail joue un rôle compensateur lors de l’évolution de la schizophrénie. D’autre part, nos résultats laissent supposer que la QV serait l’expression précoce des anomalies cérébrales induites par les processus pathologiques de la schizophrénie. / We conducted a multimodal neuroimaging approach combining the study of working memory activation with fMRI, the study of microstructural abnormalities associated with impaired QoL using MTI and the study of the functional brain substrate of QoL using SPECT. We aimed to characterize structural and functional neural basis of cognitive impairment and QoL in schizophrenia. We secondarily aimed to test the predictive value of cognitive impairment and QOL for the evolution and functioning in schizophrenia.First, we explored brain activation during a working memory task between patients with short disease duration and patients with long disease duration. We found a functional reorganization in patients with long schizophrenia duration having brain hyperactivations relative to short schizophrenia duration patients. Secondly, we investigated and compared microstructural abnormalities in patients with preserved Qol and impaired QoL. We showed that patients with impaired QoL had more microstructural changes in brain regions affected by the disease process of schizophrenia.Finally, we studied the neural substrate of QoL in schizophrenia. We reported that brain regions involved in cognitions, emotional information processing and social cognition underlie the different QoL dimensions in schizophrenia. On the one hand, our findings suggest that a functional reorganization in the working memory neural network plays a compensatory role in the schizophrenia course. On the other hand, our results suggest that QoL could be the early expression of brain abnormalities induced by the disease process of schizophrenia.

Tomografia computadorizada por emissão de fóton único (SPECT) é uma modalidade da medicina nuclear baseada na medida da distribuição espacial de um radionuclídeo. Esta técnica é amplamente utilizada em cardiologia para avaliar problemas de perfusão miocárdica, relacionados ao fluxo sanguíneo nas artérias coronárias. As imagens SPECT proporcionam melhor separação das regiões do miocárdio e facilitam a localização e a definição dos defeitos de perfusão. Um dos grandes desafios em estudos SPECT é a eficiente apresentação da informação, uma vez que um único estudo pode gerar imagens de centenas de cortes a serem analisados. Para resolver este problema, são utilizados mapas polares (também conhecidos como gráficos Bulls Eye). Mapas polares são construídos a partir de cortes tomográficos do ventrículo esquerdo e apresentam as informações dos exames de forma sumarizada, em uma imagem bidimensional. Essa dissertação apresenta um método para segmentação do ventrículo esquerdo em estudos SPECT do miocárdio e a construção de mapas polares. A segmentação do ventrículo esquerdo é realizada para facilitar o processo de geração automática de mapas polares. O método desenvolvido utiliza a transformada watershed, no contexto do paradigma de Beucher-Meyer. Para visualização dos resultados, foi desenvolvida uma aplicação, chamada Medical Image Visualizer (MIV). O MIV será disponibilizado como projeto Open Source, podendo ser livremente utilizado e/ou modificado pela comunidade de usuários, desenvolvedores e pesquisadores. / Single photon emission computed tomography (SPECT) is a nuclear medicine tomographic imaging technique based on the measurement of spatial distribution of a radionuclide. This technique is widely used in cardiology to assess myocardial perfusion problems related to blood flow in coronary arteries. SPECT images provide better separation of regions of the myocardium and facilitate the location and definition of perfusion defects. One of the major challenges in SPECT studies is the efficient presentation of information, since a single study can generate hundreds of images of slices to be analyzed. To address this issue, polar maps (also known as Bulls Eye display) are used. Polar maps are built from slices of the left ventricle and provide summarized information of exams in a two dimensional image. This dissertation presents a method for the segmentation of the left ventricle in myocardial SPECT studies and the construction of polar maps. The segmentation of the left ventricle is performed to facilitate the process of automatic generation of polar maps. The method uses the watershed transform, in the context of the Beucher-Meyer paradigm. To display the results, it was developed an application called Medical Image Visualizer (MIV). MIV will be available as an Open Source project and the communities of users, developers and researchers will be able to freely use and/or modify the application.