Dissertations / Theses on the topic 'Tomographic PIV'

Further understanding the small scale coherent structures which occur in high Reynolds number turbulence would be of enormous benefit. Therefore, the aim of the current project was to make well resolved three-dimensional flow measurements of the mixing flow between counter rotating impellers, using Tomographic Particle Image Velocimetry (TPIV).TPIV software was developed, with a novel approach permitting a significant reduction in processing time, and a series of numerical accuracy studies contributing to the fundamental understanding of this new technique. Basic flow characterisation determined the local isotropy, homogeneity and expected Reynolds number scaling. A favourable comparison between planar PIV and TPIV increased confidence in the latter, which was used to assess the dynamics and topology of the dissipation scale structures. In support of previous investigations similar topology, strain rate alignment, scale-invariance, and clustering behaviours are demonstrated. Correlated high enstrophy and dissipation regions occur in the periphery of larger structures, resulting in intermittency. Geometry characterisation indicates a predominance of tube-like structures, which are observed to form from larger ribbon-like structures through unsteady breakdown and vortex roll-up. Significant correlation between intermittent fields of dissipation and enstrophy describe the fine scales effects. These relationships should pave the way for more accurate models, capable of relating small scales and large scales during the prediction of dynamically important quantities.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
PROGRAMA DE EXCELENCIA ACADEMICA
PROGRAMA DE DOUTORADO SANDUÍCHE NO EXTERIOR
O estudo fundamental de estruturas turbulentas próximas a paredes é de significativa importância devido ao seu papel dominante em inúmeras aplicações de engenharia. Em escoamentos turbulentos, estruturas de diferentes escalas interagem entre si através de um fenômeno complexo caracterizado por um processo contínuo e auto-sustentável. Embora a presença de padrões de movimento coerente pareça ser responsável pela manutenção da turbulência, a evolução e a interação destas estruturas ainda não são completamente entendidas. Para investigar tais fenômenos, foram realizados estudos de escoamentos turbulentos próximos a paredes sobre uma placa plana em um túnel de vento e dentro de um canal de água quadrado. O presente trabalho empregou uma técnica tomográfica de velocimetria por imagem de partícula de alta taxa de medição de campos de velocidade tridimensionais. O processamento da técnica tomo-PIV foi otimizado a fim de melhorar o desempenho do algoritmo e a exatidão dos campos vetoriais medidos. As medições realizadas permitiram a obtenção de estatísticas condicionais das estruturas coerentes típicas da camada limite turbulenta, tais como regiões de baixa e de alta velocidades, varreduras (sweeps), ejeções (ejections) e vórtices. Os resultados quantitativos mostraram vórtices distribuídos por todo o escoamento, entretanto, concentrados na vizinhança das regiões de baixa velocidade e ejeções. Os resultados indicaram que os vórtices estavam indiretamente correlacionados com o processo de produção de turbulência, apesar de serem os principais responsáveis pela dissipação da energia turbulenta.
The fundamental study of turbulent structures near a wall is of significant importance due to its dominant role in innumerous engineering applications. In turbulent flows, eddies of different scales interact with each other in a complex phenomenon of a continuous self-sustaining process. Although the presence of patterns of coherent motion seem to be responsible for the maintenance of turbulence, the evolution and the interaction of these structures are still not completely understood. To investigate such phenomena, near-wall turbulent flows over a smooth at plate in a wind tunnel and inside a square water channel were conducted. The present work employed a high-repetition tomographic PIV technique to measure three dimensional, time-resolved velocity fields. The tomo-PIV processing was optimized in order to improve the algorithm performance and the vector fields accuracy. Conditional statistics of coherent structures, namely, lowand high-speed regions, sweeps, ejections and vortices, were computed. Quantitative results showed vortical structures spread all over the flow, nevertheless, concentrated close to low-speed regions and ejections. Results indicated that vortical structures were indirectly correlated with the process of turbulence production, although they were the main responsible for the turbulent energy dissipation.
L étude fondamentale des structures turbulentes proche d une paroi est d une significative importance en raison de son rôle dominant dans nombreuses applications d ingênierie. Dans les écoulements turbulents, des structures d échelles différentes interagissent dans un phénomène complexe caractérisé par un processus autonome et continu. Bien que la présence de modéles de mouvements cohérents semble entretenir la turbulence, l évolution et l interaction de ces structures ne sont pas encore complétement compris. Pour analyser ces phénomènes, l étude d écoulements turbulents à proximité de paróis a été effectuées sur une plaque plane dans une soufflerie et à l intérieur d un canal hydraulique de section carrée. Une technique tomographique de vélocimétrie par images de particules pour mesurer de champs de vitesse tridimensionnel a été employée. Le traitement des données a été optimisé afin d améliorer la précision des champs de vecteurs mesurés. Les mesures realisés ont permis d obtenir des statistiques conditionnelles des structures cohérentes, à savoir, les régions à faible et à grande vitesse, les sweeps, les ejections et les tourbillons. Les résultats quantitatives ont montré des structures tourbillonnaires distribués sur tout le ux, cependant, concentrée au voisinage des régions à faible vitesse et des ejections. Les rèsultats ont indiqué que les structures tourbillonnaires étaient indirectement corrélés avec le processus de production de la turbulence, bien qu ils ont été les principaux responsables de la dissipation d énergie turbulente.

Cette thèse porte sur le développement de la PIV tomographique (tomo-PIV) pour la mesure d’écoulements turbulents (Elsinga et al 2006). Cette méthode se fonde sur la reconstruction tomographique d’une distribution volumique d’intensité de particules traceuses, à partir de projections enregistrées par des caméras. Les distributions volumiques sont corrélées, fournissant ainsi un champ de déplacement 3D.Les principales avancées de la recherche sur cette technique sont présentées ainsi que les points bloquants. Les efforts ont principalement été portés sur la reconstruction tomographique. La principale difficulté est le bruit tomographique (particules fantômes) qui croît exponentiellement lorsqu’une forte densité de traceur est requise pour obtenir une résolution spatiale fine de la mesure, particulièrement pour les écoulements turbulents.Afin de mieux appréhender ce bruit de reconstruction, nous avons étudié numériquement les facteurs expérimentaux nuisant à la qualité de la reconstruction. Des considérations géométriques ont permis de quantifier l’impact de «particules ajoutées», qui se trouvent dans le volume de l’union mais pas dans le volume de l’intersection entre la zone laser et les champs de vue des caméras. La diminution du ratio signal-à-bruit dans les images, due à la diffusion de Mie et l’astigmatisme des optiques, a pour principal effet la perte de vraies particules dans la reconstruction.Étudier les conditions optiques de la tomo-PIV nous a permis de proposer une approche alternative à la reconstruction tomographique classique, qui vise à reconstruire une particule presque sur un unique voxel, plutôt que comme un agrégat de voxels de taille étendue, en se fondant sur une représentation particulaire des images. Nous nommons cette méthode Reconstruction Volumique de Particules (PVR). Après avoir été incorporée à un algorithme de reconstruction (SMART), il est possible d’élargir la représentation particulaire de PVR, afin d’obtenir des blobs de 2/3 voxels de diamètre requis par les algorithmes de corrélation de 3D-PIV. Des simulations numériques sur un large spectre de conditions génératrices, ont montré qu’utiliser PVR-SMART permettait des gains de performance par rapport à un algorithme classique comme tomo-SMART (Atkinson 2009).L’aspect vélocimétrie par corrélation de la méthode a aussi été pris en compte avec une extension sur GPU à la 3D (FOLKI-3D) de l’algorithme FOLKI-PIV (Champagnat et al. 2011). Le déplacement y est cherché en minimisant itérativement une fonctionnelle, du type des moindres carrés, par déformation de volume. Les tests synthétiques confirment que la réponse fréquentielle d’espace est semblable à celle d’autres algorithmes classiques itératifs de déformation de volume. Les simulations numériques de reconstruction tomographique ont permis de caractériser la robustesse de l’algorithme au bruit spécifique de la tomographie. Nous avons montré que FOLKI-3D était plus robuste aux particules fantômes cohérentes que les algorithmes classiques de déformation volumique. De plus, des gains de performance ont été observés en utilisant des schémas d’ordre élevé pour différents types de bruit.L’application de PVR-SMART sur des données expérimentales a été effectuée sur un jet d’air turbulent. Différentes densités de particules ont été utilisées pour comparer les performance de PVR-SMART avec tomo-SMART sur la région proche buse du jet. Avec le pré-traitement d’image utilisé, nous avons montré que les champs de vitesse de PVR-SMART étaient près de 50 % moins bruités que ceux de tomo-SMART. L’analyse sur les champs de vitesse comporte l’étude de quantités statistiques, de peak-locking, de divergence, du tenseur des gradients ainsi que de structures cohérentes.Enfin, nous concluons avec une synthèse des résultats obtenus au cours de cette étude, en envisageant de nouvelles perspectives de recherche dans le contexte de la PIV tomographique
This research dissertation focuses on the developments of tomographic PIV (tomo-PIV) for the measurement of turbulent flows (Elsinga et al. 2006). It is based on the tomographic reconstruction of a volumic intensity distribution of tracer particles from projections recorded on cameras. The corresponding volumic distributions are correlated to obtain 3D displacement fields.The present work surveys the state of advancement of the research conducted on this technique and the main issues it has been confronted with so far. The main research focus was on tomographic reconstruction. Indeed, its main limitation is the appearance of ghost particles, ie reconstruction noise, which occurs when high tracer concentrations are required for high spatial resolution measurements.For a thorough understanding of tomographic noise, we carried out a numerical study of experimental factors impacting the quality of tomographic reconstruction. Geometric considerations quantified the impact of "added particles" lying in the Union volume but not in the Intersection volume, between the camera fields of view and the illumination area. This phenomenon was shown to create ghost particles. The decrease in signal-to-noise ratio in the image was investigated, considering Mie scattering and defocusing effects. Particle image defocusing mainly results in the loss of real particles in reconstruction. Mie scattering’s main impact is also the loss of real particles due to the polydisperse nature of the seeding.This study of imaging conditions for tomo-PIV led us to propose an alternative approach to classical tomographic reconstruction. It seeks to recover nearly single voxel particles rather than blobs of extended size using a particle-based representation of image data. We term this approach Particle Volume Reconstruction (PVR). PVR underlies a more physical, sparse volumic representation of point particles, which lives halfway between infinitely small particles, and voxel blobs commonly used in tomo-PIV. From that representation, it is possible to smooth it to 2 voxel diameter blobs for a 3D-PIV use of PVR incorporated in a SMART algorithm. Numerical simulations showed that PVR-SMART outperforms tomo-SMART (Atkinson et al. 2009) on a variety generating conditions and a variety of metrics on volume reconstruction and displacement estimation, especially in the case of seeding density greater than 0.06 ppp.We introduce a cross-correlation technique for 3D-PIV (FOLKI-3D) as an extension to 3D of the FOLKI-PIV algorithm (Champagnat et al. 2011). The displacement is searched as the minimizer of a sum of squared differences, solved iteratively by using volume deformation. Numerical tests confirmed that spatial frequency response is similar to that of standard iterative deformation algorithms. Numerical simulations of tomographic reconstruction characterized the robustness of the algorithm to specific tomographic noise. FOLKI-3D was found more robust to coherent ghosts than standard deformation algorithms, while gains in accuracy of the high-order deformation scheme were obtained for various signal noises.The application of PVR-SMART on experimental data was performed on a turbulent air jet. Several seeding density conditions were used to compare the performance of tomo-SMART and PVR-SMART on the near field region of the jet. With the given image pre-processing, PVR-SMART was found to yield velocity fields that are about 50 % less noisy than tomo-SMART. The velocity field comparison included velocity field statistical properties, peak-locking study, flow divergence analysis, velocity gradient tensor and coherent structures exploration.Finally, conclusions are drawn from the main results of this dissertation and lead to potential research perspectives of our work with respect to the future of tomographic PIV

Les systèmes de climatisation et de ventilation sont souvent composés de configurations type jets impactant, sur leur partie terminale. Ainsi, les flux d’air soufflés viennent impacter des obstacles munis de fentes, de différentes formes, afin d’améliorer le mélange. Les conditions de confinement et de soufflage provoquent parfois un inconfort au niveau acoustique. Les nuisances acoustiques générées sont dues à un phénomène de boucles de rétroaction se traduisant par l’apparition des sons auto-entretenus. La production du son par un écoulement fluide en champ libre ou en interaction avec une structure a fait l’objet de nombreuses études. Dans le cas d’un champ acoustique et pour un écoulement à faible nombre de Mach la résolution du corollaire énergétique de Howe permet d’évaluer la puissance acoustique générée ou absorbée par les interactions entre le champ acoustique et l’écoulement. Le calcul de cette puissance nécessite la connaissance de trois paramètres : la vorticité, la vitesse et la vitesse acoustique par des méthodes analytiques ou en utilisant des données expérimentales. Expérimentalement, la mesure du champ cinématique, pour en déduire la vorticité, nécessite une technique de mesure tridimensionnelle. Pour cela une plate-forme expérimentale, utilisant de la vélocimétrie Laser, a été développée, et équipée pour générer les écoulements d’un jet plan. Les champs cinématiques de ces écoulements ont été mesurés en utilisant la technique PIV, avec un dispositif de PIV stéréoscopique. Les champs cinématiques de trente plans parallèles ont été mesurés afin d’étudier les champs de vitesses correspondants. Deux méthodes de reconstruction ont été appliquées à ces plans : la POD et la moyenne de phase. Le volume est obtenu par une interpolation des plans reconstruits donnant accès aux trois composantes de la vitesse. Pour valider ces méthodes de reconstruction en 3D à faible coût, elles étaient comparées à des mesures expérimentales réalisées par le même dispositif expérimental, dans les mêmes conditions, par la PIV tomographique donnant accès aux champs cinématiques tridimensionnels
Air conditioning and ventilation systems are often composed of jets having a configuration of an impinging jet, on their end part. Thus, the blown airflows impact slotted obstacles of different shapes to improve mixing. The conditions of confinement and blowing sometimes cause acoustic incompatibility. The acoustic noises generated are due to a phenomenon of feedback loops resulting of the appearance of self-sustained sounds. The production of sound by a free flow or in interaction with a structure has been the subject of many studies. In the case of an acoustic field and for a flow of low Mach number, Howe's energetic correlation is used to evaluate the acoustic power generated or absorbed by the interactions between the acoustic field and the flow. The calculation of this power requires the knowledge of three parameters : vorticity, velocity and acoustic velocity by analytical methods or by using experimental data. Experimentally, the measurement of the kinematic field, to deduce the vorticity, requires a three-dimensional measurement technique. For this purpose, an experimental platform, using laser velocimetry, has been developed and equipped to generate flows of a plane jet. The kinematic fields of these flows were measured using the PIV technique, with a stereoscopic PIV device. The kinematic fields of thirty parallel planes were measured to study the corresponding velocity fields. Two reconstruction methods have been applied to these plans : the POD and the phase average. The volume is obtained by an interpolation of the reconstructed planes giving access to the three components of the velocity. To validate these low-cost 3D reconstruction methods, they were compared to experimental measurements made by the same experimental setup, under the same conditions, by using the tomographic PIV giving access to the three-dimensional kinematic fields

Les mécanismes d’évolution spatio-temporelle des structures turbulentes instationnaires tridimensionnelles, et en particulier ceux rencontrés aux plus grandes échelles, sont à l’origine de phénomènes d’instabilité qui conduisent très souvent à une diminution de la performance des systèmes énergétiques. C’est le cas des variations cycle-à-cycle dans le moteur à combustion interne. Malgré les progrès substantiels réalisés par la simulation numérique en mécanique des fluides, les approches expérimentales demeurent essentielles pour l’analyse et la compréhension des phénomènes physiques ayant lieu. Dans ce travail de thèse, deux types de vélocimétrie par image de particules (PIV) ont été appliqués et adaptés au banc moteur optique du laboratoire Coria pour étudier l’écoulement en fonction de six conditions de fonctionnement du moteur. La PIV Haute Cadence 2D2C a permis d’abord d’obtenir un suivi temporel de l’écoulement dans le cylindre durant un même cycle moteur ainsi qu’identifier ces variations cycliques. La PIV Tomographique 3D3C a permis ensuite d’étendre les données mesurées vers l’espace tridimensionnel. La Tomo-PIV fait intervenir 4 caméras en position angulaire visualisant un environnement de géométrie complexe, confinée, ayant un accès optique restreint et introduisant des déformations optiques importantes. Cela a nécessité une attention particulière vis-à-vis du processus de calibration 3D des modèles de caméras. Des analyses conditionnées 2D et 3D de l’écoulement sont effectuées en se basant principalement sur la décomposition propre orthogonale (POD) permettant de séparer les différentes échelles de structure et le critère Γ permettant l’identification des centres des tourbillons
The unsteady evolution of three-dimensional large scale flow structures can often lead to a decrease in the performance of energetic systems. This is the case of cycle-to-cycle variations occurring in the internal combustion engine. Despite the substantial advancement made by numerical simulations in fluid mechanics, experimental measurements remain a requirement to validate any numerical model of a physical process. In this thesis, two types of particle image velocimetry (PIV) were applied and adapted to the optical engine test bench of the Coria laboratory in order to study the in-cylinder flow with respect to six operating conditions. First, the Time-Resolved PIV (2D2C) allowed obtaining a temporal tracking of the in-cylinder flow and identifying cyclic variabilities. Then tomographic PIV (3D3C) allowed extending the measured data to the three-dimensional domain. The Tomo-PIV setup consisted of 4 cameras in angular positioning, visualizing a confined environment with restricted optical access and important optical deformations. This required a particular attention regarding the 3D calibration process of camera models. 2D and 3D conditional analyses of the flow were performed using the proper orthogonal decomposition (POD) allowing to separate the different scales of flow structures and the Γ criterion allowing the identification of vortices centres

Die 3D Particle Tracking Velocimetry (3D PTV) ist eine Methode zur bildbasierten Bestimmung von Geschwindigkeitsfeldern in Gas- oder Flüssigkeitsströmungen. Dazu wird die Strömung mit Partikeln markiert und durch ein Mehrkamerasystem beobachtet. Das Ergebnis der Datenauswertung sind 3D Trajektorien einer großen Anzahl von Partikeln, die zur statistischen Analyse der Strömung genutzt werden können. In der vorliegenden Arbeit werden verschiedene neu entwickelte Modelle gezeigt, die das Einsatzspektrum vergrößern und die Leistungsfähigkeit der 3D PTV erhöhen. Wesentliche Neuerungen sind der Einsatz eines Spiegelsystems zur Generierung eines virtuellen Kamerasystems, die Modellierung von komplex parametrisierten Trennflächen der Mehrmedienphotogrammetrie, eine wahrscheinlichkeitsbasierte Trackingmethode sowie eine neuartige Methode zur tomographischen Rekonstruktion von Rastervolumendaten. Die neuen Modelle sind an drei realen Experimentieranlagen und mit synthetischen Daten getestet worden. Durch den Einsatz eines Strahlteilers vor dem Objektiv einer einzelnen Kamera und vier Umlenkspiegeln, positioniert im weiteren Strahlengang, werden vier virtuelle Kameras generiert. Diese Methode zeichnet sich vor allem durch die Wirtschaftlichkeit als auch durch die nicht notwendige Synchronisation aus. Vor allem für die Anwendung im Hochgeschwindigkeitsbereich sind diese beiden Faktoren entscheidend. Bei der Beobachtung von Phänomenen in Wasser kommt es an den Trennflächen verschiedener Medien zur optischen Brechung. Diese muss für die weitere Auswertung zwingend modelliert werden. Für komplexe Trennflächen sind einfache Ansätze über zusätzliche Korrekturterme nicht praktikabel. Der entwickelte Ansatz basiert auf der mehrfachen Brechung jedes einzelnen Bildstrahls. Dazu müssen die Trennflächenparameter und die Kameraorientierungen im selben Koordinatensystem bekannt sein. Zumeist wird die Mehrbildzuordnung von Partikeln durch die Verwendung von Kernlinien realisiert. Auf Grund von instabilen Kameraorientierungen oder bei einer sehr hohen Partikeldichte sind diese geometrischen Eigenschaften nicht mehr ausreichend, um die Mehrbildzuordnung zu lösen. Unter der Ausnutzung weiterer geometrischer, radiometrischer und physikalischer Eigenschaften kann die Bestimmung der 3D Trajektorien dennoch durchgeführt werden. Dabei werden durch die Analyse verschiedener Merkmale diejenigen ausgewählt, welche sich für die spatio-temporale Zuordnung eignen. Die 3D PTV beruht auf der Diskretisierung der Partikelabbildungen im Bildraum und der anschließenden Objektkoordinatenbestimmung. Eine rasterbasierte Betrachtungsweise stellt die tomographische Rekonstruktion des Volumens dar. Hierbei wird die Intensitätsverteilung wird im Volumen rekonstruiert. Die Bewegungsinformationen werden im Anschluss aus den Veränderungen aufeinander folgender 3D-Bilder bestimmt. Durch dieses Verfahren können Strömungen mit einer höheren Partikeldichte im Volumen analysiert werden. Das entwickelte Verfahren basiert auf der schichtweisen Entzerrung und Zusammensetzung der Kamerabilder. Die entwickelten Modelle und Ansätze sind an verschiedenen Versuchsanlagen erprobt worden. Diese unterschieden sich stark in der Größe (0,5 dm³ – 20 dm³ – 130 m³) und den vorherrschenden Strömungsgeschwindigkeiten (0,3 m/s – 7 m/s – 0,5 m/s)
3D Particle Tracking Velocimetry (3D PTV) is an image based method for flow field determination. It is based on seeding a flow with tracer particles and recording the flow with a multi camera system. The results are 3D trajectories of a large number of particles for a statistical analysis of the flow. The thesis shows different novel models to increase the spectrum of applications and to optimize efficiency of 3D PTV. Central aspects are the use of the mirror system to generate a virtual multi camera system, the modelling of complex interfaces of multimedia photogrammetry, a probability based tracking method and a novel method for tomographic reconstruction of volume raster data. The improved models are tested in three real testing facilities and with synthetic data. Using a beam splitter in front of the camera lens and deflecting mirrors arranged in the optical path, a four headed virtual camera system can be generated. This method is characterised by its economic efficiency and by the fact that a synchronisation is not necessary. These facts are important especially when using high speed cameras. When observing phenomena in water, there will be refraction at the different interfaces. This has to be taken into account and modelled for each application. Approaches which use correction terms are not suitable to handle complex optical interfaces. The developed approach is based on a multiple refraction ray tracing with known interface parameters and camera orientations. Mostly the multi image matching of particles is performed using epipolar geometry. Caused by the not stable camera orientation or a very high particle density this geometric properties are not sufficient to solve the ambiguities. Using further geometrical radiometrical and physical properties of particles, the determination of the 3D trajectories can be performed. After the analysis of different properties those of them are chosen which are suitable for spatio-temporal matching. 3D PTV bases on the discretisation of particle images in image space and the following object coordinate determination. A raster based approach is the tomographic reconstruction of the volume. Here the light intensity distribution in the volume will be reconstructed. Afterwards the flow information is determined from the differences in successive 3D images. Using tomographic reconstruction techniques a higher particle density can be analysed. The developed approach bases on a slice by slice rectification of the camera images and on a following assembly of the volume. The developed models and approaches are tested at different testing facilities. These differ in size (0.5 dm³ – 20 dm³ – 130 m³) and flow velocities (0.3 m/s – 7 m/s – 0.5 m/s)

Die 3D Particle Tracking Velocimetry (3D PTV) ist eine Methode zur bildbasierten Bestimmung von Geschwindigkeitsfeldern in Gas- oder Flüssigkeitsströmungen. Dazu wird die Strömung mit Partikeln markiert und durch ein Mehrkamerasystem beobachtet. Das Ergebnis der Datenauswertung sind 3D Trajektorien einer großen Anzahl von Partikeln, die zur statistischen Analyse der Strömung genutzt werden können. In der vorliegenden Arbeit werden verschiedene neu entwickelte Modelle gezeigt, die das Einsatzspektrum vergrößern und die Leistungsfähigkeit der 3D PTV erhöhen. Wesentliche Neuerungen sind der Einsatz eines Spiegelsystems zur Generierung eines virtuellen Kamerasystems, die Modellierung von komplex parametrisierten Trennflächen der Mehrmedienphotogrammetrie, eine wahrscheinlichkeitsbasierte Trackingmethode sowie eine neuartige Methode zur tomographischen Rekonstruktion von Rastervolumendaten. Die neuen Modelle sind an drei realen Experimentieranlagen und mit synthetischen Daten getestet worden. Durch den Einsatz eines Strahlteilers vor dem Objektiv einer einzelnen Kamera und vier Umlenkspiegeln, positioniert im weiteren Strahlengang, werden vier virtuelle Kameras generiert. Diese Methode zeichnet sich vor allem durch die Wirtschaftlichkeit als auch durch die nicht notwendige Synchronisation aus. Vor allem für die Anwendung im Hochgeschwindigkeitsbereich sind diese beiden Faktoren entscheidend. Bei der Beobachtung von Phänomenen in Wasser kommt es an den Trennflächen verschiedener Medien zur optischen Brechung. Diese muss für die weitere Auswertung zwingend modelliert werden. Für komplexe Trennflächen sind einfache Ansätze über zusätzliche Korrekturterme nicht praktikabel. Der entwickelte Ansatz basiert auf der mehrfachen Brechung jedes einzelnen Bildstrahls. Dazu müssen die Trennflächenparameter und die Kameraorientierungen im selben Koordinatensystem bekannt sein. Zumeist wird die Mehrbildzuordnung von Partikeln durch die Verwendung von Kernlinien realisiert. Auf Grund von instabilen Kameraorientierungen oder bei einer sehr hohen Partikeldichte sind diese geometrischen Eigenschaften nicht mehr ausreichend, um die Mehrbildzuordnung zu lösen. Unter der Ausnutzung weiterer geometrischer, radiometrischer und physikalischer Eigenschaften kann die Bestimmung der 3D Trajektorien dennoch durchgeführt werden. Dabei werden durch die Analyse verschiedener Merkmale diejenigen ausgewählt, welche sich für die spatio-temporale Zuordnung eignen. Die 3D PTV beruht auf der Diskretisierung der Partikelabbildungen im Bildraum und der anschließenden Objektkoordinatenbestimmung. Eine rasterbasierte Betrachtungsweise stellt die tomographische Rekonstruktion des Volumens dar. Hierbei wird die Intensitätsverteilung wird im Volumen rekonstruiert. Die Bewegungsinformationen werden im Anschluss aus den Veränderungen aufeinander folgender 3D-Bilder bestimmt. Durch dieses Verfahren können Strömungen mit einer höheren Partikeldichte im Volumen analysiert werden. Das entwickelte Verfahren basiert auf der schichtweisen Entzerrung und Zusammensetzung der Kamerabilder. Die entwickelten Modelle und Ansätze sind an verschiedenen Versuchsanlagen erprobt worden. Diese unterschieden sich stark in der Größe (0,5 dm³ – 20 dm³ – 130 m³) und den vorherrschenden Strömungsgeschwindigkeiten (0,3 m/s – 7 m/s – 0,5 m/s).
3D Particle Tracking Velocimetry (3D PTV) is an image based method for flow field determination. It is based on seeding a flow with tracer particles and recording the flow with a multi camera system. The results are 3D trajectories of a large number of particles for a statistical analysis of the flow. The thesis shows different novel models to increase the spectrum of applications and to optimize efficiency of 3D PTV. Central aspects are the use of the mirror system to generate a virtual multi camera system, the modelling of complex interfaces of multimedia photogrammetry, a probability based tracking method and a novel method for tomographic reconstruction of volume raster data. The improved models are tested in three real testing facilities and with synthetic data. Using a beam splitter in front of the camera lens and deflecting mirrors arranged in the optical path, a four headed virtual camera system can be generated. This method is characterised by its economic efficiency and by the fact that a synchronisation is not necessary. These facts are important especially when using high speed cameras. When observing phenomena in water, there will be refraction at the different interfaces. This has to be taken into account and modelled for each application. Approaches which use correction terms are not suitable to handle complex optical interfaces. The developed approach is based on a multiple refraction ray tracing with known interface parameters and camera orientations. Mostly the multi image matching of particles is performed using epipolar geometry. Caused by the not stable camera orientation or a very high particle density this geometric properties are not sufficient to solve the ambiguities. Using further geometrical radiometrical and physical properties of particles, the determination of the 3D trajectories can be performed. After the analysis of different properties those of them are chosen which are suitable for spatio-temporal matching. 3D PTV bases on the discretisation of particle images in image space and the following object coordinate determination. A raster based approach is the tomographic reconstruction of the volume. Here the light intensity distribution in the volume will be reconstructed. Afterwards the flow information is determined from the differences in successive 3D images. Using tomographic reconstruction techniques a higher particle density can be analysed. The developed approach bases on a slice by slice rectification of the camera images and on a following assembly of the volume. The developed models and approaches are tested at different testing facilities. These differ in size (0.5 dm³ – 20 dm³ – 130 m³) and flow velocities (0.3 m/s – 7 m/s – 0.5 m/s).

Le travail mené dans le cadre de cette thèse porte sur l’étude expérimentale et numérique de l’écoulement au sein d’un éjecteur supersonique. Le régime d’écoulement qui s’installe dans ces appareils est très complexe du fait des phénomènes physiques qui les caractérisent comme la turbulence et les ondes de choc. Les méthodes expérimentales utilisées sont la mesure de la pression le long de l’axe de l’éjecteur `a l’aide d’une sonde développée à cet effet, la visualisation de l’écoulement par tomographie laser et la mesure de vitesse par PIV. Les simulations numériques sont réalisées à l’aide du code Ansys-Fluent en 2D axisymétrique et en 3D. Dans un premier temps, une étude de sensibilité du modèle numérique portant sur les paramètres de simulations et les modèles de turbulence est menée sur l’éjecteur fonctionnant sans flux induit. La validation des simulations repose sur une comparaison des résultats numériques avec des mesures de vitesse par PIV. Un modèle 3D s’est avéré incontournable pour l’étude de l’écoulement dans l’éjecteur avec flux induit à cause de sa géométrie complexe. Les outils expérimentaux et numériques développés permettent d’analyser finement l’interaction des flux moteur et induit, en particulier les processus de recompression par chocs obliques et de mélange. Une tentative de modélisation par LES des instabilités de l’écoulement détectées expérimentalement est également abordée
The work reported in this thesis relates to the experimental and numerical studies of the flow within a supersonic ejector. The flow pattern which occurs in these apparatuses is very complex because of the flow phenomena encountered like flow turbulence and shock waves. The experimental methods used are the measurement of the pressure along the axis of the ejector using a specific probe developed for this purpose, the flow visualization by laser tomography and the velocity measurement by PIV. The numerical simulations are carried out using the Ansys-Fluent code with 2D axisymmetric and 3D models. First, a study of sensitivity to the numerical parameters of simulation and to the turbulence models is carried out on the ejector operating without induced flow. The validation of the simulations is achieved by a comparison between the numerical results and velocity measurements by PIV. A 3D model is necessary for the simulation of the flow in the ejector operating with induced flow because of the complex ejector geometry. The experimental techniques and the numericalmodels developed make it possible to analyze the interaction of the primary and secondary flows, in particular the process of recompression by oblique shocks and the mixing process. An attempt at modeling by LES simulation the flow instabilities detected during experiments is also approached

Locomotion is a key characteristic of almost all forms of life and is often accomplished, whether on land, in water, or in the air, by reciprocal motion of two or more appendages. Among the zooplankton, many species propel themselves by rhythmically beating multiple pairs of closely spaced leg-like appendages in a back-to-front (metachronal) pattern. The focus of this study is to understand the mechanical design, kinematic operation, and hydrodynamic result of metachrony in the zooplankton. In the first part of this study, Antarctic krill (Euphausia superba) are investigated as an ecologically important model species that metachronally beats its swimming legs (pleopods) to perform drag-based propulsion. Based on high speed videos of freely swimming Antarctic krill, hovering, fast forward swimming, and upside down swimming are identified as three distinct swimming modes with significantly different stroke amplitudes and beat frequencies. When transitioning between hovering and fast forward swimming, Antarctic krill first increase beat amplitude and secondarily increase beat frequency. In considering the design components that contribute to metachrony being a successful swimming technique, a comparison among many different species shows that the ratio between the appendage separation distance and appendage length is limited to a narrow range of values (i.e. 0.2 - 0.65). In the second part of this study, metachrony is examined at smaller length and time scales by examining the impulsive escape jump of a calanoid copepod (Calanus finmarchicus). The wake generated by the copepod's metachronally beating swimming legs is experimentally measured using a novel (and newly developed) tomographic particle image velocimetry (PIV) system capable of making volumetric 3D velocity measurements with high temporal and spatial resolution using IR illumination. The flow generated by the escaping copepod consisted of a stronger posterior vortex ring generated by the metachronally stroking swimming legs and a weaker one generated anteriorly around the body by the impulsive start of the escape, both of which decayed over time. The experiments also revealed azimuthal asymmetry in the vortices caused by body yawing and the action of the swimming legs, flow features not considered in previous axisymmetric computational and theoretical models of copepod jumps. While not accounting for this asymmetry, an impulsive stresslet is nonetheless useful in modeling the flow created by the escaping copepod and represents the flow more accurately than an impulsive Stokeslet. In the final part of this study, the flow associated with metachronal hovering in Antarctic krill is experimentally and theoretically investigated in regards to the energy requirements of the pelagic lifestyle. Volumetric flow measurements of a hovering Antarctic krill show that each stroking pleopod drags flow behind it such that a downward stream develops medially. The lateral exopodites induce tip vortices which add to the lift force on each appendage. Furthermore, the flow beneath the hovering krill develops into a pulsed jet with a Strouhal number in the 'high-efficiency zone' of 0.2 < St < 0.4. Actuator disk theory is used to make theoretical estimates of the induced power necessary to hover, the results of which match induced power values calculated from measured flow gradients contributing to viscous energy dissipation.

The fuel assemblies used at the Swedish nuclear power plants contain typically between 100 and 300 fuel rods. An experimental technique has been demanded for determining the relative activities of specific isotopes in individual fuel rods without dismantling the assemblies. The purpose is to validate production codes, which requires an experimental relative accuracy of <2 % (1 σ).

Therefore, a new, non-destructive tomographic measurement technique for irradiated nuclear fuel assemblies has been developed. The technique includes two main steps: (1) the gamma-ray flux distribution around the assembly is recorded, and (2) the interior gamma-ray source distribution in the assembly is reconstructed. The use of detailed gamma-ray transport calculations in the reconstruction procedure enables accurate determination of the relative rod-by-rod source distribution.

To investigate the accuracy achievable, laboratory equipment has been constructed, including a fuel model with a well-known distribution of ¹³⁷Cs. Furthermore, an instrument has been constructed and built for in-pool measurements on irradiated fuel assemblies at nuclear power plants.

Using the laboratory equipment, a relative accuracy of 1.2 % was obtained (1 σ). The measurements on irradiated fuel resulted in a repeatability of 0.8 %, showing the accuracy that can be achieved using this instrument. The agreement between rod-by-rod data obtained in calculations using the POLCA–7 production code and measured data was 3.1 % (1 σ).

Additionally, there is a safeguards interest in the tomographic technique for verifying that no fissile material has been diverted from fuel assemblies, i.e. that no fuel rods have been removed or replaced. The applicability has been demonstrated in a measurement on a spent fuel assembly. Furthermore, detection of both the removal of a rod as well as the replacement with a non-active rod has been investigated in detail and quantitatively established using the laboratory equipment.

Ce travail porte sur l'étude expérimentale et numérique de jets coaxiaux de rapports de vitesses débitantes intérieure/extérieure) inférieurs à l’unité, présentant une rotation dans le jet annulaire. Dans un premier temps, des visualisations par tomographie laser ont été réalisées dans les plans méridien et transversaux permettant une description tridimensionnelle de l'écoulement. Pour différents nombres de Reynolds, de rapport de vitesses et de nombre de Swirl, un inventaire des modes dominants a pu être établi. Les champs instantanés de vitesses ont ensuite été mesurés par Vélocimétrie par Imagerie de Particules (PIV). Les résultats de mesures de vitesses longitudinales et azimutales moyennées en temps sont présentés. Une comparaison avec les structures observées par tomographie est proposée. Une décomposition de Fourier a été effectuée permettant d'identifier les modes dominants ainsi que leur position dans la direction radiale. L'approche expérimentale a été suivie par une analyse de stabilité linéaire. Une attention particulière est portée sur l'état de base stationnaire reconstruit à partir des profils de vitesses mesurées par PIV à la sortie du jet. Étant donné que l'écoulement est non parallèle, une approche globale de la stabilité est utilisée. L'étude de la stabilité est basée sur la résolution numérique des équations de Navier-Stokes par des méthodes pseudo-spectrales. L'objectif de cette analyse est de retrouver la carte en mode de Fourier azimutaux observée expérimentalement. Nous nous sommes donc intéressés au taux de croissance le plus élevé de la perturbation pour chaque mode azimutal ainsi qu'à la nature convective/ absolue des modes. Pour finir, une com
This work concerns the experimental and numerical study of coaxial jets with outer to inner velocity ratio lower than unity, presenting a rotation in the annular jet. At first, flow visualizations by tomography laser were used in the meridian and transverse plans in order to provide a spatial description of the flow. For various values of the nondimensional parameters : numbers of Reynolds, outer to inner velocity ratio and Swirl number, an inventory of the dominant modes was be established. Instantaneous velocity fields were then measured by Particle lmaging Velocimetry (PIV). The results of longitudinal and azimuthal time-averaged Velocity fields are presented. A comparison with the structures observed by tomography is proposed. A Fourier decomposition was made allowing to identify the dominant modes as well as their position in the radial direction. Experimental investigation was followed by a linear stability analysis. Special attention is paid to the steady base-flow solution reconstructed from the velocity profiles measured by PIV at the end of the nozzle. Given that the is not parallel, a global approach was used. Study of the stability is based on the numerical solution of the incompressible Navier-Stokes equations with pseudo-spectral methods. The objective of this analysis is to the map of azimuthal Fourier modes observed experimentally. We were thus interested in the most amplified growth rate of the disturbance for every azimuthal mode as well as in the absolute/convective nature of the modes. To conclude, a comparison of the results obtained in both numerical and experimental approaches is proposed

The North Anatolian Fault Zone (NAFZ) in Turkey is a major continental strike-slip fault, 1200 km long and with a current slip rate of 25 mm/yr. Historical records show that the NAFZ is capable of producing high-magnitude earthquakes, activating different segments of the fault in a westward progression. Currently, the NAFZ poses a major seismic hazard for the city of Istanbul, which is situated close to one of the two strands into which the fault splays in northwestern Turkey. Understanding of fault zone structure and properties at depth is essential to constrain where deformation occurs within the lithosphere and how strain localises with depth. In fact, geodynamic models explaining surface deformation require knowledge of the width and depth extent of the fault zone in both the crust and upper mantle. In this framework, this thesis aims to provide better constraints on fault zone geometry within the lithosphere. To achieve this objective P and S wave teleseismic tomography have been applied to the data recorded by a dense array of broadband seismic stations (DANA, Dense Array for Northern Anatolia); through teleseismic tomography it was possible to image the NAFZ structure in both the crust and uppermost mantle. In addition, joint inversion i of P-wave teleseismic data and local earthquake data collected using the same array provided a greatly improved resolution within the upper 20 km of the crust. Results from this work highlighted the presence of a shear zone associated to the northern branch of the NAFZ in the study area. The fault zone appears to be 15 km wide within the upper crust and narrows to < 10 km within the lower crust and to Moho depth. In the uppermost mantle its width is constrained to be 30 to 50 km.

In einem Verbundprojekt im Rahmen des Programms „Energie 2020+“ gefördert durch das BMBF koordiniert durch das HZDR arbeiteten 4 Universitäten, 2 Forschungszentren und ANSYS zusammen. Der vorliegende Bericht beschreibt die Arbeiten des HZDR, die im Zeitraum September 2009 bis Januar 2013 durchgeführt wurden. Das Vorhaben war auf die Entwicklung und Validierung von CFD-Modellen von unterkühltem Sieden bis zu Filmsieden gerichtet. Im Bericht werden die entwickelten und verwendeten Modelle dargestellt. Anhand der Nachanalyse von Experimenten wird auf die vorgeschlagene Kalibrierung der Modelle eingegangen. Wichtig ist hierbei eine genauere Beschreibung der Zwischenphasengrenzfläche, die durch Kopplung des Wandsiedemodells mit einem Populationsmodell erreicht werden kann. Anhand der Analyse von Bündelexperimenten konnte gezeigt werden, dass die gemessenen querschnittsgemittelten Messwerte mit einem Satz im Rahmen der Modellunsicherheiten kalibrierter Modellparameter reproduziert werden kann. Für die Berechnung der Verteilungsmuster des Dampfgehaltes im Kanalquerschnitt muss die Modellierung der Turbulenz beachtet werden. Die experimentellen Arbeiten waren auf die Untersuchung eines Brennelementbündels gerichtet. An einer Versuchsanordnung zu einem Brennelementbündel werden die turbulente einphasige Geschwindigkeit (PIV), der mittlere Gasgehalt (Gamma-Densitometrie) sowie der zeitlich und räumlich aufgelöste Gasgehalt (Hochgeschwindigkeits-Röntgentomographie) gemessen. Letztere Methode wurde in Rossendorf entwickelt.

Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.

The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.

Screening of breast cancer patients for their tumour's prognostic marker status is necessary in determining the most suitable course of treatment. This is particularly important in the assessment of HER-2 expression status in identifying candidates who may respond to trastuzumab therapy. Current methods are limited in their effectiveness in accurately determining actual marker status.Discussed herein is an investigation into the development of a titanium dioxide nanoparticle system which may be applied as a medical imaging methodology through the use of positron emission tomography to gauge accurately a patient's HER-2 expression status in identifying candidates for trastuzumab therapy. The initial synthesis of organically coated ultra-small titanium dioxide nanoparticles is discussed in depth with respect to a range of coating molecules and further functionalisation. Additionally, methodology to elicit an exchange of these coat molecules is explored in detail resulting in the generation of TiO2 nanoparticles capable of forming long-term stable suspensions in water. An exploration of the synthesis of fluoride accepting groups for use in generating radiolabelled compounds is explored both successfully and unsuccessfully leading to the development of conditions suitable for radiolabelling aryltrifluoroborate compounds. Attempts to then combine these radionuclide accepting groups with biologically compatible TiO2 nanoparticles are discussed as an initial step toward the generation of a potential PET tracer. However, while this conjugation was achieved, a successful demonstration of the radiolabelling was not achieved requiring further focus on modulating the nanoparticle to easily allow its recovery from such reactions. Finally, an investigation into the effects of trastuzumab and cetuximab on FDG uptake by cells in vitro is discussed with respect to the potential of monitoring disease response to these drugs with conventional FDG-PET.

Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. Although the exact pathogenesis of AD remains unclear, accumulation of β- amyloid (Aβ) plaques seems to be among the causative events. In view of this, Aβ- PET imaging is considered to be a powerful non-invasive diagnostic tool that could also contribute to the development of therapies by monitoring responses. However, Aβ-PET ligands approved so far can only detect heavy plaque load and cannot replace post-mortem examination of brain tissue. The aim of this multidisciplinary study was to develop structurally novel PET tracers for AD. We focused on barbiturates for two main reasons: (i) barbiturates have an excellent ability to cross the blood-brain-barrier, (ii) they are chelators of cations involved in AD. A group of seven “cold” fluorinated barbiturates, along with the corresponding precursors for the “hot” radiosyntheses, was designed and synthesised. All the experimental logP values fell into the optimum range for brain uptake. Barbiturate 1a (Figure I) was selected for further investigations. Upon assessment of its affinity and specificity for Aβ, the radiosynthesis of [18F]1a was optimised. The imaging potential of this tracer was investigated in vivo in pre-clinical mouse models of AD. Brain PET/CT scans with [18F]1a showed reproducible brain uptake and clearance in three different mouse genotypes (WT, APP/PS1 and PLB2-Tau). The significantly higher uptake observed in APP/PS1 mice provided evidence for (i) the in vivo targeting of Aβ- plaques and (ii) the specificity of the tracer towards Aβ pathology. Finally, we designed a second-generation of barbiturates incorporating stilbene groups as dual metal/Ab targeting tracers and we developed a partial synthesis. With this study we paved the way for a larger scale research endeavour that may ultimately result in the rational design of an optimised lead tracer with the potential to ultimately translate into clinical use.

A novel class of potential positron emission tomography (PET) radiotracers for imaging aminopeptidase N (also known as APN or CD13) and cannabinoid type 1 (CB1) receptors were designed and synthesised with an efficient chemical strategy. Both targets have remarkable diagnostic and therapeutic potential, in fact the CD13 receptors are over-expressed during tumour angiogenesis and the CB1 receptors are highly expressed in the brain playing important functions in several pathophysiological processes. The target compounds were obtained by means of oxime-bio-conjugation between fluoro-deoxy-carbohydrates, used as prosthetic groups, and hydroxylamine-functionalised cyclic NGR (asparagine-glycine-arginine) motif sequences for CD13 receptor and rimonabant-type pyrazoles for the CB1 receptor. In particular, aminooxy-cyclic NGR peptides were conjugated with the novel prosthetic group 5-FDR (5-fluoro-5-deoxy-D-ribose) and the aminooxy- pyrazole-type cannabinoid molecules were conjugated with both 5-FDR and with FDG (2-fluoro-2-deoxy-D-glucose). 5-FDR proved to be superior to FDG, as the bioconjugation reaction occurred in milder conditions (room temperature vs 100 °C) and at faster rate. Furthermore, we observed that the rate of the oxime bond formation depends on the solubility of the aminooxy-functionalized core used. In fact, the bioconjugation with hydrophilic cyclic aminooxy-NGR peptides was faster than in the case of lipophilic aminooxy-pyrazoles (10 min vs 20-30 min). The receptor affinity is decreased in the case of the CB1 receptors after conjugation with the fluoro-carbohydrates. This is not observed with the conjugated NGR peptides, which maintain similar affinity for the CD13 receptor compared with the unconjugated NGR. In conclusion, we have developed an efficient strategy for the synthesis of a novel class of CD13 ligands, which may be also produced in radiofluorinated form, and explored a novel bioconjugation strategy for CB1 receptor ligands. Both may have important applications in the development of PET tracers.

In recent years tumour hypoxia has been extensively investigated, mainly because it is a source of resistance to the common radio and chemo therapies. In fact, the low levels and heterogeneous distribution of oxygen in hypoxic microenvironment render ionizing radiation ineffective in treating cell proliferation. Furthermore, a low oxygen concentration promotes the activation of HIF-1 transcription factor, which favours the development of a more malignant and resistant cancer cell phenotype often associated with poor prognosis. Positron Emission Tomography (PET) imaging is a valuable diagnostic tool for investigating hypoxia in vivo by means of radiotracers, which incorporates both a radioisotope and a hypoxia-sensitive function. The aim of this multidisciplinary project was to develop small libraries of radiolabelled compounds starting from the biological and chemical features of the two gold standard hypoxia PET tracers [18F]FMISO and [18F]FAZA as well as those of the promising new tracer [18F]HX4. These new radiocompounds display the following peculiar structural characteristics: a 2-nitroimidazole hypoxia-sensitive moiety, different spacers to modulate steric constraint, lipophilicity and metabolic stability and a fluorinated aldopentose sugar as prosthetic group (e.g. [18F]FDR). Two series of compounds were designed and developed based on the conjugation method used to introduce the prosthetic group, namely the oxime bond formation and the thiazolidine ring closure. Six radiotracers belonging to the oxime-derivatives series were tested in vitro on MCF7 breast cancer cell lines in hypoxic conditions and a lead radiocompound incorporating a cyclopropyl group was identified. This new hypoxia tracer showed a better kinetic profile than both [18F]FMISO and [18F]FAZA in MCF7 cancer cell lines and comparable uptake values on a panel of different cancer cell lines, up to 120 min post administration at 1% of O2. These promising results will pave the way for futures in vivo studies.

A wide range of conditions are characterised by focal neurological symptoms, yet the pathophysiolgy often remains poorly understood. This thesis has focussed on applying functional neuroimaging in clinical groups. Migraines with aura are amongst the most common conditions posing a significant burden to sufferers. Elevated connectivity was detected in the visual cortex of migraine with aura patients, potentially complementing one of the leading proposed mechanisms for attacks. Minor strokes patients are also affected by focal symptoms after events which in some cases can be prolonged. Altered connectivity was observed in a number of regions reflecting previous findings for acute stroke. A group of transient ischaemic attack patients were also analysed, revealing subtle differences necessitating further study. Lastly disorders of consciousness pose acute challenges for treatment and ongoing care. Task based imaging was applied to form a more accurate picture of residual cognition. Additionally the correlation between measures derived from resting state data and cerebral glucose consumption was explored.

Cancer is the second deadliest disease in the United States with an estimated 1.69 million new cases in 2017. Medical imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), are widely used in clinical medicine to detect, diagnose, plan treatment, and monitor tumors within the body. Advances in imaging research related to cancer assessment have largely relied on consented human patients, often including varied populations and treatments. Tumor bearing mouse models have been highly valued for basic science research, but imaging focused applications are limited by the translational ability of micro imaging systems. Pig models are well suited to bridge the gap between human cohorts and mouse models due to similar anatomy, physiology, life-span, and size between pigs and humans. These models provide the opportunity to advance medical imaging while simultaneously characterizing progressive changes resulting from an intervention, exposure, or genetic modification. We present a foundation for effectively characterizing disease models in pigs, susceptible to tumor development, using longitudinal medical image acquisition and post-processing techniques for quantification of disease. Longitudinal, whole-body protocols were developed with CT and MRI. Focus was placed on systematic process, including transportation, anesthesia and positioning, imaging, and environmental controls. Demonstration of the methodology was achieved with six pigs (30-85 kg) with four to seven imaging time points acquired per animal. Consistent positioning across time points (CT to CT) and within time points (CT to MRI) was assessed with distance measures obtained from the skeleton following rigid registration between images. Alignment across time points was achieved with an average value of 16.51 (± 12.46) mm observed all acquired measurements. For consistent, retrievable, and complete qualitative assessment of acquired images, structured reports were developed, including assessment of imaging quality and emphasis on tumor development throughout the body. Reports were used to perform a systematic, semi-qualitative comparison of CT and MRI lung assessment with an overall agreement of 72% in detection of disease indicators. A multi-level registration algorithm was developed to align anatomic structures of interest in the acquired longitudinal datasets. The algorithm consisted of initialization followed by repeated application of a core registration framework as the input data reduced in image field of view. It was applied to align regions of interest in the brain, upper right lung, and right kidney. Validation was performed with overlap (range = [0.0,1.0], complete overlap = 1) and distance measures (range = [0.0, ∞], perfect match = 0.0) of corresponding segmentations with overall results of 0.85 (± 0.11) and 0.41 (± 0.83) mm, respectively. An extension of the algorithm was created, demonstrating the ability to incorporate directional growth and feature extraction measurements into longitudinal tumor progression monitoring. Techniques were applied to a phantom dataset showing solid tumor growth and transition from a non-solid to part-solid lesion in the lungs. Finally, the developed methods – imaging, structured reporting, registration, and longitudinal feature extraction – were applied to four different porcine models pre-disposed to tumor development. 1) A genetically modified Li-Fraumeni (TP53R167H/+/TP53R167H/R167H) background model showing the development of osteosarcoma and lymphoma. 2) A TP53R167H/+ animal with exposure to crystalline silica showing progression of silicosis in the lungs. 3) TP53R167H/+/TP53R167H/R167H animals with exposure to radiation for targeted sarcoma development and 4) TP53R167H/+ pigs with conditional KRASG12D/+ mutation activated in the lung and pancreas. Whole-body and targeted imaging protocols were developed for each model and qualitatively interpreted by a radiologist using structured reports. Multi-level registration was used to align identified tumors and longitudinal features were extracted to quantitatively track change over time. Overall, the developed methods aided in the effective, non-invasive characterization of these animals.

Negli ultimi decenni, la ricerca e lo sviluppo di nuove fonti di energia sono state oggetto di crescente interesse scientifico. In particolare, la fusione nucleare potrebbe essere la soluzione al problema energetico mondiale. ITER è attualmente il più grande esperimento di fusione nucleare in via di costruzione. Situato nel sud della Francia, sarà il più grande tokamak costruito al mondo con l'obiettivo di produrre 500 MW di potenza dai 50 MW di potenza fornitagli. Diversi metodi di riscaldamento del plasma sono in via di sviluppo per poter scaldare il core del plasma a temperature dell'ordine dei 15 keV. Tra questi, l'iniezione di fasci neutri è uno dei più importanti. Il progetto PRIMA, costituito dagli esperimenti SPIDER e MITICA in via di costruzione al Consorzio RFX a Padova, si pone come obiettivo lo studio dei futuri iniettori di fasci neutri di ITER. L'esperimento NIO1, anch'esso situato al Consorzio RFX, è una relativamente piccola sorgente a radio frequenza RF di ioni negativi, nato con l'obiettivo di caratterizzare la fisica delle sorgenti di ioni nell'ottica dei futuri utilizzi negli iniettori di fasci neutri, quali lo stesso MITICA. Questo lavoro di tesi, nato da una collaborazione tra i Laboratori Nazionali di Legnaro (LNL) e il Consorzio RFX, caratterizza il fascio di ioni negativi di NIO1. I dati raccolti durante le campagne sperimentali sono stati analizzati e confrontati, per testare le performance della nuova griglia di estrazione installata su NIO1 a maggio 2017. La caratterizzazione è stata fatta in diversi modi: confrontando qualitativamente i dati raccolti dalle varie diagnostiche; ricostruendo tomograficamente l'immagine dei 9 beamlets tramite i dati raccolti dalle telecamere; caratterizzando il plasma formatosi in seguito alla propagazione del fascio nel gas di fondo, tramite il confronto con i dati sperimentali e quelli ottenuti da una simulazione numerica Particles-In-Cell PIC.

Laparoscopic operations are a common and popular way for abdominal procedures. They are usually performed by insufflation of carbon dioxide (CO2) into the abdominal cavity. However, insufflation of CO2 may interfere with cardiac and circulatory as well as respiratory functions. The CO2-pneumoperitoneum (PP) may cause hypercarbia and acidosis. The direct effects of CO2 and acidosis lead to decreased cardiac contractility, sensitization of the myocardium to arrhythmogenic effects of catecholamines and systemic vasodilatation. There may even be long-lasting post-operative effects on breathing control. The pneumoperitoneum may also cause several respiratory changes, e.g. decreased functional residual capacity (FRC) and vital capacity (VC), formation of atelectasis, reduced respiratory compliance and increased airway pressure. Still, arterial oxygenation is mostly maintained or even improved during PP. In view of the apparently contradictory results in respiratory mechanics and gas exchange, the present studies were performed to evaluate respiratory changes on gas exchange and ventilation-perfusion distributions during PP in a porcine model. It was demonstrated that atelectasis during anaesthesia and PP may be estimated by an increased arterial to endtidal PCO2-gradient (study I). Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better ventilation-perfusion match (study II). Increasing abdominal pressure shifted blood flow more and more away from collapsed lung tissue, decreased pulmonary shunt and improved oxygenation from 8 to 16 mmHg PP, despite an increase of atelectasis formation (study III). CO2-PP enhanced the shift of blood flow towards better ventilated parts of the lung compared to Air-PP. Moreover, sodium natriumprusside worsened the ventilation-perfusion match even more and blunted the effects previously seen with carbon dioxide. CO2 should therefore be the mediator of enhancing HPV during PP. In conclusion, pneumoperitoneum with CO2 causes atelectasis with elimination of ventilation in the dependent lung regions. However, an efficient shift of blood flow away from collapsed, non-ventilated regions results in a better ventilation-perfusion matching and better oxygenation of blood than without PP. A prerequisite for the beneficial effect is the use of carbon dioxide for the abdominal inflation, since it enhances HPV.

A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com insuficiência respiratória e necessidade de ventilação mecânica invasiva (VMI). A mortalidade desta síndrome é elevada, mas pode ser reduzida com o uso de estratégias protetoras de ventilação mecânica que usam baixo de volume corrente (VC), geralmente 6ml/Kg ou menos, para minimizar a lesão causada pelo ventilador. Algumas destas estratégias de ventilação protetora utilizam valores elevados de PEEP que podem produzir instabilidade hemodinâmica. O objetivo deste estudo foi comparar, em um modelo experimental suíno de SDRA, os efeitos hemodinâmicos causados por duas estratégias de ventilação mecânica protetora: uma que utiliza PEEP ajustado pela Tomografia de Impedância Elétrica (OLA) e a outra, a mais comumente utilizada na prática clínica (ARDSNET), em que a PEEP é ajustada através de uma tabela. Foram utilizados 17 animais após randomização (8 no grupo OLA; 9 no grupo ARDSNET) que foram ventilados por 42 horas. As variáveis foram analisadas utilizando ANOVA de medidas repetidas. Antes da radomização, os grupos não apresentavam diferenças nos parâmetros hemodinâmicos e respiratórios. Considerando o período de 42 horas de estudo: 1) o grupo OLA utilizou valores maiores de PEEP, obteve uma melhor oxigenação, mas com valores de PaCO2 mais elevado; não houve diferença entre os grupos para o platô de pressão, mas o delta de pressão foi menor no grupo OLA o que pode minimizar o risco de lesão pulmonar induzida pelo ventilador; 2) o grupo OLA apresentou valores de índice cardíaco (IC) menores durante o estudo, mas não houve um comprometimento aos órgãos alvos conforme pode ser constatado pelos valores normais do lactato arterial e pelos valores de saturação do sangue venoso misto maiores do que no grupo ARDSNET; 3) pela análise de regressão múltipla pode se observar que o aumento da PEEP esteve associado com aumento da pressão média de artéria pulmonar (PMAP), mas redução do IC e da pressão arterial média, enquanto que o aumento da PaCO2 esteve associado com um aumento da PMAP e do IC. Concluímos que uma estratégia ventilatória protetora para SDRA cujo ajuste de PEEP é guiado por TIE, quando comparada com outra estratégia protetora comumente utilizada na prática clínica por um período de 42 horas, determina uso de valores maiores de PEEP, o que melhora a oxigenação e minimiza o delta de pressão, mas causa redução do IC que não resulta em isquemia tecidual.
The Acute Respiratory Distress Syndrome (ARDS) is associated with respiratory failure and need for invasive mechanical ventilation (IMV). The mortality of this syndrome is high, but can be reduced with the use of protective strategies of mechanical ventilation using low tidal volume (VT), usually 6ml/Kg or less, to minimize the damage caused by the ventilator. Some of these strategies of protective ventilation use high levels of PEEP that can produce hemodynamic instability. The aim of this study was to compare, in an experimental pig model of ARDS, the hemodynamic effects caused by two strategies of protective ventilation: one strategy adjusts PEEP values using Electrical Impedance Tomography (EIT-OLA) and the other, the most commonly used in clinical practice (ARDSNET), in which PEEP is adjusted through a table. Seventeen animals were randomized (8 in OLA group; 9 in ARDSNET group) that were ventilated for 42 hours. The variables were analyzed using repeated measures ANOVA. Before randomization, the groups had no difference in hemodynamic and respiratory parameters. Considering the period of 42 hours of study: 1) OLA group used higher values of PEEP, had a better oxygenation but with higher values of PaCO2; there was no difference between groups for the plateau pressure, but the delta pressure was lower in OLA group which can minimize the risk for ventilator-induced lung injury; 2) the OLA group showed lower values of cardiac index (CI) during the study, but there was no damage to target organs as showed by normal blood lactate values and values of mixed venous blood saturation greater than in ARDSNET; 3) multiple regression analysis revealed that, increasing PEEP was associated with increasing in mean pulmonary artery pressure (MPAP), but reduction CI and mean arterial pressure, while increasing in PaCO2 was associated with an increase in MPAP and CI. We conclude that a protective ventilatory strategy for ARDS whose setting of PEEP is guided by EIT, when compared with other protective strategy commonly used in clinical practice for a period of 42 hours requires the use of higher values of PEEP, which improves oxygenation and minimizes delta pressure, but causes reduction of CI that does not result in tissue ischemia.

Les ``C-arm'' sont des systémes de radiologie interventionnelle fréquemment utilisés en salle d'opération ou au lit du patient. Des images 3D des structures anatomiques internes peuvent être calculées à partir de multiples radiographies acquises sur un ``C-arm mobile'' et isocentrique décrivant une trajectoire généralement circulaire autour du patient. Pour cela, la géométrie conique d'acquisition de chaque radiographie doit être précisément connue. Malheureusement, les C-arm se déforment en général au cours de la trajectoire. De plus leur motorisation engendre des oscillations non reproductibles. Ils doivent donc être calibrés au cours de l'acquisition. Ma thèse concerne la calibration intrinsèque d'un C-arm à partir de la détection de la projection du collimateur de la source dans les radiographies.Nous avons développé une méthode de détection de la projection des bords linéaires du collimateur. Elle surpasse les méthodes classiques comme le filtre de Canny sur données simulées ou réelles. La précision que nous obtenons sur l'angle et la position (phi,s) des droites est de l'ordre de: phi{RMS}=+/- 0.0045 degrees et s{RMS}=+/- 1.67 pixels. Nous avons évalué nos méthodes et les avons comparés à des méthodes classiques de calibration dans le cadre de la reconstruction 3D
Mobile isocentric x-ray C-arm systems are an imaging tool used during a variety of interventional and image guided procedures. Three-dimensional images can be produced from multiple projection images of a patient or object as the C-arm rotates around the isocenter provided the C-arm geometry is known. Due to gravity affects and mechanical instabilities the C-arm source and detector geometry undergo significant non-ideal and possibly non reproducible deformation which requires a process of geometric calibration. This research investigates the use of the projection of the slightly closed x-ray tube collimator edges in the image field of view to provide the online intrinsic calibration of C-arm systems.A method of thick straight edge detection has been developed which outperforms the commonly used Canny filter edge detection technique in both simulation and real data investigations. This edge detection technique has exhibited excellent precision in detection of the edge angles and positions, (phi,s), in the presence of simulated C-arm deformation and image noise: phi{RMS} = +/- 0.0045 degrees and s{RMS} = +/- 1.67 pixels. Following this, the C-arm intrinsic calibration, by means of accurate edge detection, has been evaluated in the framework of 3D image reconstruction

Bone is a common site for metastases and spine represent the most frequent site. Lytic lesions are associated with the loss of bone tissue, which can compromise the mechanical competence of the vertebra, leading to spine instability. Rigid stabilization is a solution, but it is a complex surgery, that can be very critical for oncologic patients; on the other hand, an untreated metastasis can lead to mechanical failure of the bone, leading to pain, immobilization and in the worst case, paralysis. In this study, a protocol to analyse the strain with simulated lytic metastasis under compressive loading has been developed and optimized using a porcine vertebra. The strain distribution has been measured experimentally using micro-computed tomography (micro-CT) and Digital Volume Correlation (DVC), which provided three-dimensional displacements and strains maps inside the specimen. The ideal parameters for the DVC have been found by analysing two repeated scans in constant strain condition and setting a target of 200 microstrain for the errors (one order of magnitude lower than typical strains in bone subjected to physiological loading conditions). An ideal nodal spacing of 50 voxels (approximately 2 mm) has been chosen and a voxel detection algorithm has been applied to all data to remove regions outside the bone. In order to understand how the presence of the defect could alter the strain distribution, the porcine vertebra has also been subjected to non-destructive compressive load before and after the preparation of a mechanically induced lytic metastasis in the vertebral body. An increase of the 40% of the compressive principal strain after the defect has been found in proximity of the lesion. This protocol will be used in future studies to analyse the effect of size and position of artificially metastatic lesions in the vertebral body of human spines.

We investigate experimentally the turbulent flow through a two-dimensional contraction. Using a water tunnel with an active grid we generate turbulence at Taylor microscale Reynolds number Reλ ~ 250 which is advected through a 2.5:1 contraction. Volumetric and time-resolved Tomo-PIV and Shake-The-Box velocity measurements are used to characterize the evolution of coherent vortical structures at three streamwise locations upstream of, and within the contraction. We confirm the conceptual picture of coherent large-scale vortices being stretched and aligned with the mean rate of strain. This alignment of the vortices with the tunnel centerline is stronger compared to the alignment of vorticity with the large-scale strain observed in numerical simulations of homogeneous turbulence. We judge this by the peak probability magnitudes of these alignments. This result is robust and independent of the grid-rotation protocols. On the other hand, while the point-wise vorticity vector also, to a lesser extent, aligns with the mean strain, it principally remains aligned with the intermediate eigen-vector of the local instantaneous strain-rate tensor, as is known in other turbulent flows. These results persist when the distance from the grid to the entrance of the contraction is doubled, showing that modest transverse inhomogeneities do not significantly affect these vortical-orientation results.

Tomographic Particle Image Velocimetry Using Colored Shadow Imaging by Meshal K Alarfaj, Master of Science King Abdullah University of Science & Technology, 2015 Tomographic Particle image velocimetry (PIV) is a recent PIV method capable of reconstructing the full 3D velocity field of complex flows, within a 3-D volume. For nearly the last decade, it has become the most powerful tool for study of turbulent velocity fields and promises great advancements in the study of fluid mechanics. Among the early published studies, a good number of researches have suggested enhancements and optimizations of different aspects of this technique to improve the effectiveness. One major aspect, which is the core of the present work, is related to reducing the cost of the Tomographic PIV setup. In this thesis, we attempt to reduce this cost by using an experimental setup exploiting 4 commercial digital still cameras in combination with low-cost Light emitting diodes (LEDs). We use two different colors to distinguish the two light pulses. By using colored shadows with red and green LEDs, we can identify the particle locations within the measurement volume, at the two different times, thereby allowing calculation of the velocities. The present work tests this technique on the flows patterns of a jet ejected from a tube in a water tank. Results from the images processing are presented and challenges discussed.

Over the last 30 years, Particle Image Velocimetry (PIV) has become the most powerful tool to study velocity fields in fluid mechanics. This technique is non-intrusive requiring seeding the flow with small tracer particles. The hardware required for these sophisticated PIV methods is very expensive (CCD or CMOS high-speed cameras and lasers), and the present dissertation aims to develop novel and inexpensive alternatives. The first part of this work investigates the use of multiple smartphones as a lower-cost Tomographic-PIV system for reconstructing 3D-3C velocity fields. We use colored shadows to imprint two or three different time-steps on the same image in a RGB-backlit configuration. We use commercially available Tomo-PIV software for the calibration, 3-D particle reconstruction, and particle-field correlations, to obtain three velocity components in a volume. The proposed system is tested with a vortex ring and the results are compared to stereoscopic-PIV for error estimations. We expand this work to a high-speed time-resolved setup to obtain 3D-3C velocity fields in time. This improvement is possible using newer smartphones capable of recording high-speed video at HD resolution. The challenges of using such cameras are presented and tackled. The illumination system, testing flow and image processing is similar to the one presented in the first section. A benchmark of the smartphone system is carried out comparing it to a Tomo-PIV system capable of recording 4K video resolution. A different approach is proposed to reconstruct a 3D-3C velocity field using a single color video camera. This technique uses chromatic structured light with color-gradients projected perpendicularly with respect to the color camera. Thus, we encode the depth position of the particles with a different wavelength of light. Different light sources are used to produce such color gradients. Finally, a variation of the previous technique is tested using a single monochromatic camera and structured volumetric illumination with spatially varying intensity profiles. This technique enables us to encode the depth position of every particle in their intrinsic brightness. The proposed system can achieve a depth resolution of 200 levels, i.e., an order of magnitude higher than previously proposed systems.

Oscillating-foil hydrokinetic turbines have gained interest over the years to extract energy from renewable sources. The influence of the sweep angle on the performance of a fully-passive oscillating-plate hydrokinetic turbine prototype was investigated experimentally in the present work. The sweep angle was introduced to promote spanwise flow along the plate in order to manipulate the leading edge vortex (LEV) and hydrodynamically optimize the performance of the turbine. In the present work, flat plates of two configurations were considered: a plate with a 6° sweep angle and an unswept plate (control), which were undergoing fully-passive pitch and heave motions in uniform inflow at the Reynolds numbers ranging from 15 000 to 30 000. The resulting kinematic parameters and the energy extraction performance were evaluated for both plates. Planar (2D) particle image velocimetry (PIV) was used to obtain patterns of the phase-averaged out-of-plane vorticity during the oscillation cycle. The circulation in the wake was then related to the induced-forces on the plate by calculating the moments of vorticity of the LEV with respect to the pitching axis of the plate. Tomographic (3D) PIV was implemented in evaluating the influence of the spanwise flow on the dynamics of the vortex structure in three-dimensional space. The rate of deformation of the vortex length was quantified by calculating the deformation terms embedded in the vorticity equations, then linked to the stability of the vortex. The results show evidence of delay of the shedding of LEV and increased vortex stability, in the case of the swept plate. The manipulation of the LEV by the spanwise flow was related to the induced kinematics exhibited by the prolonged heave forces experienced by the swept plate, which led to the higher power extraction performance at high inflow velocities. In the presence of spanwise flow, positive vortex stretching along the vortex line increased the stabilization of the vortex core and prevented the onset of helical vortex breakdown, observed in the case of the unswept plate. The use of the sweep profile on the plate has led to the improvement of energy extraction performance of the fully-passive hydrokinetic turbine.
Graduate

Indiana University-Purdue University Indianapolis (IUPUI)
Introduction: In order to successfully treat an infected root canal system (RCS), it is required to locate all root canals and have an access path to the apex of each canal. This can be challenging in teeth with pulp canal obliteration (PCO), often leading to increased chair time and increased risk of iatrogenic errors. Guided endodontic access (GEA) combines information from a cone-beam computed tomography (CBCT) scan with an intra-oral scan to create a stent. GEA stents with or without fixation pins have been shown to be successful in accurately negotiating a RCS with PCO. Objective: Compare the degree of deviation and difference in 3D offset at the base to apical tip of the drill from the designed access path when a GEA stent with and without pin fixation is used to access tooth #8 with PCO. Materials and Methods: A 3-D printed maxillary model of an anonymous patient had a GEA stent designed using coDiagnonstiX software. The stent extended from tooth #3 to tooth #14 with the guide sleeve over tooth #8. Tooth #8 with no calcification, calcification to the cervical third, and calcification to the middle third of the RCS were designed in the coDiagnostiX software. Tooth #8 will be accessed using a 1.3 mm drill that fits a 1.3 mm sleeve used for both access and pin fixation. 15 of the 30 GEA samples will utilized pin fixation, while the other 15 samples did not utilize pin fixation. Following GEA in all 30 samples a CBCT was taken of each sample. Each post-operative CBCT was aligned with the pre-operative CBCT in the coDiagnostiX software. The coDiagnostiX software was able to calculate the degree of deviation and difference in 3D offset between the base and apical tip of the drill during GEA. Paired t-tests were used to test each group for significant differences in 3D offset between base and tip. Two-way ANOVA was used to evaluate the effects of pin fixation and calcification on the degree of deviation and the deviation of 3D offset of the entry point and tip. Results: There was a significant interaction between use of pin fixation and calcification level on the degree of deviation of GEA. GEA with pin fixation had a significantly larger degree of deviation than GEA without pin fixation with calcification extending to the middle third of the RCS. GEA with and without pin fixation did not have a significant difference when calcification extended to the cervical third of the RCS or no calcification was present. There was a significant interaction between use of pin fixation and calcification level on 3D offset difference. GEA with pin fixation had a significantly larger 3D offset difference than GEA with no pin fixation for calcification in the middle third of the RCS. For GEA with and without pin fixation there was no significant difference when calcification extended to the cervical third of the RCS or no calcification was present. Conclusion: The use of pin fixation did not result in a decrease of degree of deviation or difference in 3D offset during GEA access. It can be concluded that the use of pin fixation is not necessary for GEA of teeth with PCO when a full dentition is present to provide stability and retention of the stent.

Trabalho de Projeto do Mestrado Integrado em Engenharia Biomédica apresentado à Faculdade de Ciências e Tecnologia
A doença de Alzheimer (AD) é a doença neurodegenerativa responsável pelo maior número de casos de demência. Tomografia por emissão de positrões (PET) com 11C-Pittsburgh Compound B (PiB) e 11C-(R)-PK11195 (PK) são duas modalidades utilizadas na visualização das placas amilóides e da microglia ativada no cérebro humano, respetivamente. Uma vez que as placas amilóides são o principal identificador da AD e que a microglia ativada é também recorrentemente encontrada no cérebro dos doentes de Alzheimer, estes representam dois potenciais biomarcadores imagiológicos que podem ser usados como ferramenta de diagnóstico precoce da doença. Este trabalho teve como objetivo principal a resolução de um problema de classificação binário, entre controlos saudáveis (HC) e pacientes de Alzheimer, através de métodos de machine learning (ML) baseados em dois traçadores imagiológicos de PET: o PiB e o PK. Outro objetivo deste trabalho, incluiu a identificação das regiões cerebrais onde o PiB e o PK apresentam maior correlação, quer a nível do voxel quer a nível regional. O dataset deste estudo, que incluiu 41 indivíduos (20 doentes de Alzheimer e 21 HC), foi dividido em três grupos por forma a melhor compreender o impacto do intervalo de tempo considerado no protocolo de aquisição da PET. O grupo TOT, composto pelas imagens PET adquiridas durante o tempo total de biodistribuição do PiB, e os grupos 4070 e 4060, compostos por imagens PET adquiridas durante o intervalo de tempo caraterístico de acumulação de cada um destes radiofármacos. Após quantificação, pré-processamento, extração e seleção das features, as features selecionadas das imagens PET, com PiB e com PK, foram utilizadas como variáveis preditoras em classificadores baseados em support vector machines (SVM). Para estudar o impacto das diferentes regiões de referência utilizadas na normalização de imagens PET com PK, e a influência do método de quantificação escolhido, os grupos de AD e HC de diferentes formas de quantificação de imagens PET com PK foram comparados a nível do voxel. Adicionalmente, calculou-se para diferentes regiões cerebrais a correlação existente entre imagens PET com PiB em termos da taxa do valor de captação padronizado (SUVr) e as imagens PET com diferentes formas de quantificação PK.O classificador com o melhor desempenho foi construído com features extraídas de imagens PET com PiB do grupo 4070 normalizadas pelo cerebelo (exatidão – 0.925, sensibilidade-1.000, especificidade-0.857). Por conseguinte, para imagens PET com PiB, o cerebelo foi a região cerebral onde a diferença na acumulação de amilóides entre os grupos de AD e HC foi a menos significativa, isto é, foi a melhor região de referência. De referir que quando o cerebelo é utilizado como região de referência em imagens PET com PiB, é verificada uma maior correlação a nível regional para com as imagens PET com PK, comparativamente à normalização realizada através da matéria branca. As features extraídas a nível regional de imagens PET com PK não melhoraram nem a exatidão nem a sensibilidade do classificador apenas baseado em features extraídas de imagens PET com PiB. A correlação a nível regional entre imagens PET com PiB e com PK sugere que o cerebelo apresenta uma ligação específica ao PK; consequentemente, o método supervised cluster analysis algorithm based on four kinetic classes (SVCA4) relevou ser a melhor abordagem para a normalização de imagens PET com PK. As duas formas de quantificação de imagens PET com PK apresentaram diferenças muito pouco significativas entre os grupos AD e HC a nível do voxel, o que sugere que a biodistribuição do PK no cérebro não permite diferenciar grupos. Esta afirmação apoia a associação que se tem vindo a estabelecer entre a microglia ativada e a neuroinflamação. Como a neuroinflamação é característica de cada indivíduo, isto é, é aleatoriamente distribuída no cérebro dos doentes de Alzheimer, o esperado é a não diferenciação de grupos por parte do PK. Foram encontradas cinco regiões cerebrais onde a correlação a nível do voxel se relevou elevada para quase todas as regiões de referência consideradas, córtex motor primário, córtex visual primário, córtex de associação somatossensorial, córtex visual associativo e córtex pré-motor. Tanto o precuneus (P) como o lóbulo parietal inferior (PI) desempenham funções importantes no processamento visual e espacial. Por conseguinte, é natural que os resultados da correlação a nível regional estejam associados com os obtidos a nível do voxel.Em suma, de acordo com o estudo realizado, o classificador construído apenas com features extraídas de imagens PET com PiB do grupo 4070, usando o cerebelo como região de referência, foi o classificador que apresentou uma melhor resposta ao problema proposto, classificação binária de indivíduos como AD ou HC. Adicionalmente, também foi descoberta uma correlação positiva entre o PK e o PiB em regiões cerebrais responsáveis pela função motora e pelo processamento visual.
Alzheimer’s disease (AD) is one of the main neurodegenerative disorders causing dementia. Positron emission tomography (PET) neuroimaging with 11C-Pittsburgh Compound B (PiB) and 11C-(R)-PK11195 (PK) are two of the existing modalities to assess amyloid plaque and activated microglia in human brain, respectively. Since amyloid plaque is the main hallmark of AD and activated microglia is currently found in the brain of AD patients, these imaging biomarkers can be used in diagnostic workup and to achieve early AD diagnosis.The main goal of the present study is to solve a binary classification problem between healthy controls (HC) and AD patients, by using machine learning (ML) methods based on two PET imaging biomarkers, PiB and PK. Another important goal of this work includes the identification of the brain regions where PiB and PK are most correlated, at both regional and voxel level.In the present study it was included 41 subjects (20 AD and 21 HC). To understand the impact of the time interval considered in PET image acquisition, the dataset was split in three different groups. Group TOT composed by PiB PET images acquired during the total time of PiB biodistribution, and groups 4070 and 4060, acquired during the characteristic accumulation time of PiB and PK, between minute 40 and 70, and 40 and 60, after administration, respectively. After quantification, pre-processing, feature extraction and selection, PiB and PK PET images were submitted to classification using a support vector machines (SVM) approach. Voxel-wise comparison between AD and HC groups of different quantified PK PET images were performed to understand the impact of distinct reference regions in the normalization of PK PET images and the influence of the quantification method used. Also, voxel-wise and region of interest (ROI) based correlation between standard uptake value ratio (SUVr) PiB and different quantified PK PET images were calculated.Normalization by cerebellum of PiB PET images of group 4070 yielded the best classification accuracy of AD (accuracy-0.925, sensitivity-1.000, specificity-0.857). Thus, for PiB PET images, cerebellum appears to be the brain region where amyloid accumulation bears the least significant differences between HC and AD patients, i.e., the best reference region to do the normalization. Also, when using the cerebellum as reference region of PiB PET images, stronger ROI-based correlation with binding potential (BP) PK PET images in several brain regions was found, compared to normalization based on white matter. Features extracted at regional level from PK PET images did not show improvement, neither in accuracy nor in sensitivity, of the classifier only based on features extracted from PiB PET images. ROI-based correlation results suggest specific binding of PK to cerebellum; thus, supervised cluster analysis algorithm based on four kinetic classes (SVCA4) showed to be the best approach to do the normalization of PK PET images. Both types of quantified PK PET images did not show significant differences between groups at voxel level. This suggests that PK biodistribution in the brain is not relevant for group differentiation. The reason why is probably related to the fact that activated microglia is associated with neuroinflammation, and this process is quite variable across participants, i.e., it is randomly distributed across brains of AD patients. There were five brain regions where the correlation at voxel level between PK and SUVr PiB PET images agreed the most for all reference regions considered, primary motor cortex, primary visual cortex, somatosensory association cortex, associative visual cortex and premotor cortex. Since, both precuneus (P) and parietal inferior (PI) have important roles in visuospatial processing, ROI-based correlation results are consistent with the ones obtained at voxel level.Overall, according with the present study, the classifier only based on features extracted from PiB PET images of group 4070, using cerebellum as reference region, was the classifier who solved more accurately the problem proposed, binary classification in AD. Additionally it was also found a positive correlation between PK and PiB in particular in brain regions responsible for motor function and visual processing.
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