This work is aimed at deposition of fibers, which are able to penetrate deeper in the human respiratory airways and cause health hazards. Opening chapters are dedicated to classification of aerosols, human lung anatomy basics and methods for measurement of micrometer-sized aerosols. An experiment was carried out to investigate the deposition of fibers. Fibers were delivered into the silicon cast of the human airways and data of deposition fraction and efficiency were acquired. A new method was established to acquire the data. This method works on a principle of image analysis. Results of the new method were compared with a standard method, which follows a methodology NIOSH 7400.

Das zentrale Thema dieser Dissertation ist die Anwendung illustrativer Methoden auf zwei bisher ungelöste Probleme der Strömungsvisualisierung. Das Ziel der Strömungsvisualisierung ist die Bereitstellung von Software, die Experten beim Auswerten ihrer Strömungsdaten und damit beim Erkenntnisgewinn unterstützt. Bei der illustrativen Visualisierung handelt es sich um einen Zweig der Visualisierung, der sich an der künstlerischen Arbeit von Illustratoren orientiert. Letztere sind darauf spezialisiert komplizierte Zusammenhänge verständlich und ansprechend zu vermitteln. Die angewendeten Techniken werden in der illustrativen Visualisierung auf reale Daten übertragen, um die Effektivität der Darstellung zu erhöhen. Das erste Problem, das im Rahmen dieser Dissertation bearbeitet wurde, ist die eingeschränkte Verständlichkeit von komplexen Stromflächen. Selbstverdeckungen oder Aufrollungen behindern die Form- und Strömungswahrnehmung und machen diese Flächen gerade in interessanten Strömungssituationen wenig nützlich. Auf Basis von handgezeichneten Strömungsdarstellungen haben wir ein Flächenrendering entwickelt, das Silhouetten, nicht-photorealistische Beleuchtung und illustrative Stromlinien verwendet. Interaktive Flächenschnitte erlauben die Exploration der Flächen und der Strömungen, die sie repräsentieren. Angewendet auf verschiedene Stromflächen ließ sich zeigen, dass die Methoden die Verständlichkeit erhöhen, v.a. in Bereichen komplexer Strömung mit Aufwicklungen oder Singularitäten. Das zweite Problem ist die Strömungsanalyse des Blutes aus 4D PC-MRI-Daten. An diese relativ neue Datenmodalität werden hohe Erwartungen für die Erforschung und Behandlung kardiovaskulärer Krankheiten geknüpft, da sie erstmals ein dreidimensionales, zeitlich aufgelöstes Abbild der Hämodynamik liefert. Bisher werden 4D PC-MRI-Daten meist mit Werkzeugen der klassischen Strömungsvisualisierung verarbeitet. Diese werden den besonderen Ansprüchen der medizinischen Anwender jedoch nicht gerecht, die in kurzer Zeit eine übersichtliche Darstellung der relevanten Strömungsaspekte erhalten möchten. Wir haben ein Werkzeug zur visuellen Analyse der Blutströmung entwickelt, welches eine einfache Detektion von markanten Strömungsmustern erlaubt, wie z.B. Jets, Wirbel oder Bereiche mit hoher Blutverweildauer. Die Grundidee ist hierbei aus vorberechneten Integrallinien mit Hilfe speziell definierter Linienprädikate die relevanten, d.h. am gefragten Strömungsmuster, beteiligten Linien ausgewählt werden. Um eine intuitive Darstellung der Resultate zu erreichen, haben wir uns von Blutflußillustrationen inspirieren lassen und präsentieren eine abstrakte Linienbündel- und Wirbeldarstellung. Die Linienprädikatmethode sowie die abstrakte Darstellung der Strömungsmuster wurden an 4D PC-MRI-Daten von gesunden und pathologischen Aorten- und Herzdaten erfolgreich getestet. Auch die Evaluierung durch Experten zeigt die Nützlichkeit der Methode und ihr Potential für den Einsatz in der Forschung und der Klinik. / This thesis’ central theme is the use of illustrative methods to solve flow visualization problems. The goal of flow visualization is to provide users with software tools supporting them analyzing and extracting knowledge from their fluid dynamics data. This fluid dynamics data is produced in large amounts by simulations or measurements to answer diverse questions in application fields like engineering or medicine. This thesis deals with two unsolved problems in flow visualization and tackles them with methods of illustrative visualization. The latter is a subbranch of visualization whose methods are inspired by the art work of professional illustrators. They are specialized in the comprehensible and esthetic representation of complex knowledge. With illustrative visualization, their techniques are applied to real data to enhance their representation. The first problem dealt with in this thesis is the limited shape and flow perception of complex stream surfaces. Self-occlusion and wrap-ups hinder their effective use in the most interesting flow situations. On the basis of hand-drawn flow illustrations, a surface rendering method was designed that uses silhouettes, non-photorealistic shading, and illustrative surface stream lines. Additionally, geometrical and flow-based surface cuts allow the user an interactive exploration of the surface and the flow it represents. By applying this illustrative technique to various stream surfaces and collecting expert feedback, we could show that the comprehensibility of the stream surfaces was enhanced – especially in complex areas with surface wrap-ups and singularities. The second problem tackled in this thesis is the analysis of blood flow from 4D PC-MRI data. From this rather young data modality, medical experts expect many advances in the research of cardiovascular diseases because it delivers a three-dimensional and time-resolved image of the hemodynamics. However, 4D PC-MRI data are mainly processed with standard flow visualizaton tools, which do not fulfill the requirements of medical users. They need a quick and easy-to-understand display of the relevant blood flow aspects. We developed a tool for the visual analysis of blood flow that allows a fast detection of distinctive flow patterns, such as high-velocity jets, vortices, or areas with high residence times. The basic idea is to precalculate integral lines and use specifically designed line predicates to select and display only lines involved in the pattern of interest. Traditional blood flow illustrations inspired us to an abstract and comprehensible depiction of the resulting line bundles and vortices. The line predicate method and the illustrative flow pattern representation were successfully tested with 4D PC-MRI data of healthy and pathological aortae and hearts. Also, the feedback of several medical experts confirmed the usefulness of our methods and their capabilities for a future application in the clinical research and routine.

As an intrinsic requirement for digital image correlation (DIC)to be applicable, the images must exhibit a speckle pattern of sufficient unique features. Researchers have incorporated X-ray phase contrast imaging (PCI) and DIC (XDIC) and conducted studies on materials with natural internal features as speckles. This study is the first attempt to explore the applicability and standards of XDIC to be applied on materials that are transparent under X-ray PCI, mainly polymers, by deliberately embedding particles into the sample. The goal is to generate a high-quality speckle while maintaining the least influence on the material’s properties. Iron oxide (FeO), tungsten carbide (WC), and platinum (Pt) are embedded into Sylgard® epoxy at various weight ratios, and the Sylgard® samples are loaded with a Kolsky compression bar paired with high-speed X-ray PCI. The speckle quality of the PCI images is assessed using a mean intensity gradient based approach, as well as intensity distribution analysis. DIC is applied to the images to measure the displacement field in the loading direction, and the results are analyzed. The engineering stress-strain relationship is generated from the Kolsky bar apparatus, and the results are compared to find the influence of the added particles.<div><br></div><div>The results indicate thatthe addition of particles does not significantly alter the base polymer’s properties, and the theoretical deviation error can be as low as less than 0.01 pixels. Disregarding the limited applicability to embed into polymer samples, platinum produces the best speckle. WC particle is the superior choice of material to embed for its good speckle quality, ease of embedding, and good availability. Lower weight ratios are shown to be preferential. This study also emphasizes the importance of sample design when applying XDIC to materials with embedded particles. It is preferential for best accuracy to design the region of interest to be away from the surfaces of the samples and be located near the back of the sample with respect to the impact surface.<br></div>

In this work, a characterization and optimization of the grating-based x-ray imaging technique is presented. The investigations are introduced by analytical considerations, are underpinned with numerical simulations and validated using exemplary experiments. A detailed examination of the image formation in a grating interferometer is given, highlighting the dependence of the measured signal on the profile of the gratings. Subsequently, it is shown analytically and in experiments that grating-based imaging can be performed using three basic grating arrangements, which differ in their requirements on grating fabrication and experimental implementation. By a characterization of the measurement signal for each arrangement, a dependence of the signal strength on the sample position within the interferometer is identified. The consecutive evaluation of the impact of this position dependence on radiographic and tomographic data leads to the derivation of optimized reconstruction algorithms and to a correction of resulting image artifacts. Additionally, it is shown that the simultaneous measurement of attenuation and phase images allows the determination of the atomic number of the sample, opening new possibilities for material discrimination. Apart from these investigations on the contrast formation, various imperfections of the technique are investigated: The properties of the image noise are examined in a detailed statistical analysis, yielding a fundamental understanding of the signal-to-noise behavior of the three available contrast channels. Additionally, beam-hardening artifacts at polychromatic x-ray sources are investigated and their correction by a linearization approach is resented. By a subsequent analysis of the influence of various different grating imperfections on the image quality, tolerance limits for grating fabrication are specified. Furthermore, analytical considerations show that gratings with a duty cycle of 1/3 are advantageous with respect to the signal-to-noise ratio in comparison to common gratings with a duty cycle of 1/2. In conclusion, the results, concepts and methods developed in this work broaden the understanding of grating-based x-ray imaging and constitute a step forward towards the practical implementations of the technique in imaging applications.

The present study analyses three beam shaping approaches with respect to a light-efficient generation of i) patterns and ii) multiple spots by means of a generic optical 4f-setup. 4f approaches share the property that due to the one-to-one relationship between output intensity and input phase, the need for time-consuming, iterative calculation can be avoided. The resulting low computational complexity offers a particular advantage compared to the widely used holographic principles and makes them potential candidates for real-time applications. The increasing availability of high-speed phase modulators, e.g. on the basis of MEMS, calls for an evaluation of the performances of these concepts. Our second interest is the applicability of 4f methods to high-power applications. We discuss the variants of 4f intensity shaping by phase modulation from a system-level point of view which requires the consideration of application relevant boundary conditions. The discussion includes i) the micro mirror based phase manipulation combined with amplitude masking in the Fourier plane, ii) the Generalized Phase Contrast, and iii) matched phase-only correlation filtering combined with GPC. The conceptual comparison relies on comparative figures of merit for energy efficiency, pattern homogeneity, pattern image quality, maximum output intensity and flexibility with respect to the displayable pattern. Numerical simulations illustrate our findings.

<p>    </p> <p>Cerebral aneurysms are presented in 3-5% of the population and account for approximately 10% of all strokes. The clinical decision on treating unruptured aneurysms should not be taken lightly because a majority of the asymptomatic cerebral aneurysm will not rupture, while both endovascular and microsurgical treatments carry the risk of morbidity and mortality. Thus, there is a need for objective risk assessment to reliably predict the high-risk aneurysms to intervene. Recent studies have found that the blood flow hemodynamic metrics such as pressure and wall shear stress (WSS) are related to the growth and rupture of the aneurysms. 4D flow magnetic resonance imaging (MRI) measures time-resolved three-dimensional velocity fields in the aneurysms <em>in vivo</em>, allowing for the evaluation of hemodynamic parameters. This work presents the developments of flow-physics constrained data enhancement and augmentation methods for 4D flow MRI to assist the risk stratification of cerebral aneurysms. First, a phase unwrapping and denoising method is introduced to enhance the dynamic range and accuracy of 4D flow MRI velocity measurement by incorporating the divergence-free constraint of incompressible flow. Moreover, methods are developed to improve the estimation of hemodynamic parameters from 4D flow data including pressure and WSS. The pressure reconstruction method is also applied to the flow data acquired using particle imaging velocimetry (PIV) and particle tracking velocimetry (PTV) and shows superior performance as compared to the existing methods by solving the pressure Poisson equation. We also proposed a framework to estimate the uncertainty of the PIV/PTV based pressure estimation by propagating the velocity uncertainty. In addition, a multi-modality approach is introduced to enhances the resolution and accuracy of 4D flow data with sparse representation, which improves the reliability of the hemodynamic evaluation. Finally, we present a method to measure the left ventricular flow propagation velocity from cardiac imaging to help in assessing the diastolic function. </p>

La tomographie par rayons X est une technique d’imagerie non-invasive qui permet de réaliser des images en 3D par l’acquisition de multiples images en 2D. La tomographie X par contraste de phase (XPCT) a été utilisée pour étudier la biodistribution de nanoparticules métalliques (NPs) dans des souris. Ces NPs sont très utilisées comme radiosensibilisants dans la recherche de traitements contre les cancers mais aussi pour marquer des plaques amyloïdes de la maladie d’Alzheimer chez la souris. Grace à la grande brillance du synchrotron ESRF, des images XPCT en haute résolution ont été obtenues et traitées pour produire des modèles en 3D d’organes de souris dopés aux NPs de gadolinium, d’or ou de platine.En parallèle, dans le cadre du projet Européen VOXEL (Volumetric X-ray Extremely Low dose), un microscope compact à rayons X mous a été développé pour l’imagerie cellulaire. Ce microscope fonctionne dans la « fenêtre de l’eau », une région spectrale pour laquelle un bon contraste de la structure cellulaire est réalisable naturellement. Ce microscope est conçu pour réaliser de l’imagerie plénoptique, une technique actuellement testée uniquement dans le visible. Ce système est composé d’une lentille principale et d’une matrice de micro-lentilles couplée à un détecteur, permettant d’enregistrer les composantes angulaires et spatiales des rayons arrivant au niveau du détecteur. Il est ainsi possible de produire des images en 3D à partir d’une seule exposition. Adapter cette technique disruptive aux rayons X aura, un très grand impact pour les applications biomédicales car cela permettra de réduire fortement la dose absorbée par les échantillons par rapport à la méthode conventionnelle de tomographie X. / X-ray tomography is a non-invasive imaging technique that allows producing 3D images following the acquisition of multiple 2D images at many angles. In particular, X-ray Phase-Contrast Tomography (XPCT) has been exploited for resolving the biodistribution of metal-based theranostic nanoparticles (NPs) in mice. These NPs are widely used as radiosensitizers for researches on cancer therapies and, recently to mark amyloid plaques in Alzheimer’s disease in mice. Thanks to the high brightness of ESRF synchrotron, high resolution XPCT images were obtained and thus processed for producing 3D models of mice organs doped with gadolinium, gold or platinum NPs.In parallel, in the framework of a European project, named VOXEL (Volumetric X-ray Extremely Low dose), a compact desktop-size soft X-ray microscope was developed aiming at biological cell imaging. The microscope was designed to be suitable in the so-called “water window” spectral range, where a natural good contrast of the cellular structures is achievable. The microscope was conceived to perform plenoptic imaging, a technology currently tested only in the visible domain. This device is composed of a main lens and a microlens array coupled to a detector, allowing recording the spatial and the angular components of the light rays travelling up to the detector and thus enabling producing 3D images in a single exposure. By adapting this disrupting technology to X-rays, a huge impact for bio-medical applications is foreseen, since it would lead to a drastic decrease of the dose absorbed by samples, compared to traditional X-ray tomography methods.

Ce manuscrit détaille le développement d'un montage de pince optique permettant d'étudier les propriétés mécaniques des cellules endothéliales, impliquées dans le développement de l'athérosclérose. Le but est de déterminer les propriétés viscoélastiques des cellules, et de suivre la propagation d’une contrainte mécanique au sein de la cellule. Cette contrainte mécanique est appliquée via une bille liée à la membrane de la cellule et soumise à un piège optique.Le dispositif réalisé combine le piégeage optique et la microscopie à contraste de phase, permettant d'exercer une force tout en imageant les cellules via le même objectif de microscope. L'originalité du montage de pince optique repose sur la détection du signal rétrodiffusé par la bille piégée, dans un plan conjugué du plan focal arrière de l'objectif, afin de mesurer la position relative de la bille par rapport au piège.Une part importante de ce travail a consisté à comprendre l'allure du signal détecté présentant un système d'interférences en anneaux, et à l’expliquer par un modèle simple. Ce modèle a permis de comprendre la présence d’artefacts de mesure de position dus à la superposition de l'anneau de phase sur la figure d’interférence. Pour y remédier, l'anneau de phase est déporté dans un plan conjugué intervenant uniquement dans l'imagerie de l'échantillon.La figure d'interférence présente un atout majeur : elle donne accès à la hauteur précise de la bille piégée, généralement difficile à mesurer. Cette information est nécessaire pour calibrer la constante de raideur du piège optique à la hauteur des cellules, que ce soit par l'analyse de la densité spectrale de puissance du mouvement brownien de la bille piégée ou par sa réponse à un échelon de position du piège. Ces deux méthodes de calibration, ainsi que l'application du théorème d’équipartition et l'analyse par inférence bayésienne, ont été mises en œuvre. Tous les résultats s'avèrent en bon accord. La calibration complète du dispositif en fait un outil prêt à l'emploi pour exercer des forces locales contrôlées en direction et en amplitude sur les cellules. / This manuscript details the development of an optical tweezer setup to study the mechanical properties of endothelial cells, involved in the development of atherosclerosis. The goal is to determine the viscoelastic properties of the cells, and to follow the propagation of the mechanical constraint inside the cell. This mechanical constraint is applied via a bead attached to the cell membrane and subjected to an optical trap.The setup built combines optical trapping with phase contrast microscopy, to apply a force while imaging the cells with the same microscope objective. The originality of the optical tweezer setup relies on the detection of the signal backscattered by the trapped bead, in a plane conjugate to the back focal plane of the objective, in order to measure the relative position of the bead with respect to the center of the trap.An important part of this work was dedicated to the understanding of the detected signal presenting an interference pattern with rings, explained by a simple model. This model provides an explanation for the position measurement artifacts arising from the superposition of the phase ring and the interference pattern. To solve the problem, the phase ring was moved in a conjugate plane involved only in the imaging path of the sample.The interference pattern has the main advantage of giving access to the precise height of the trapped bead, usually difficult to measure. This information is necessary to calibrate the optical trap stiffness at the height of the cells, either by the power spectrum analysis of the Brownian motion of the trapped bead, or by its response to a step motion of the trap. These two calibration methods, along with the application of the equipartition theorem and Bayesian inference analysis, were implemented and their results compared, showing a good agreement. The complete calibration of the setup makes it a ready-to-use tool to exert local forces controlled in direction and amplitude on cells.

Despite decades of research of normal pressure hydrocephalus (NPH), a clear pathophysiological mechanism of the disease is sill unknown. This results in the absence of a unambiguous diagnostic biomarker. Moreover, NPH in contrast to similar neurodegenerative diseases is curable by insertion of a ventrikulo-peritoneal shunt. Now the diagnostics is based on invasive functional testing, on the contrary, imaging methods play only a supporting role. This work is processed with an effort to find a sufficiently sensitive and specific biomarker of MRI imaging using advanced analytical methods. For this reason, the structural volumetry and the phase contrast method were tested. The individual partial results of both of these modalities have already been described in the literature, but the conclusions were controversial. The main contribution of this work is the range of tested parameters and their to date untested advanced analysis - accurate automatic segmentation in volumetric study and machine learning algorithms in phase contrast study. In a volumetric study, we segmented a total of 26 structures in 74 patients (29 with diagnosed NPH, 45 without NPH). In the case of preoperative examination, we demonstrated statistically significant differences in the size of the left hippocampus, corpus callosum, left...

<p>  </p> <p>Polymer bonded explosives (PBX) are a particle reinforced composite containing a high solids loading of explosive particulates bound in a polymer matrix. Commercially produced energetic particulates contain some percentage of flaws in the form of contaminants, porosity, and preexisting fractures. Additional large-scale porosity within the composite is generated during PBX formulation. The introduction of novel additive manufacturing techniques to the energetics field alters the known composite structure and introduces a porosity variable that has not been fully characterized. Porosity collapse during deformation is believed to be a predominant mechanism for hotspot formation, which dominates shock initiation behaviors. These phenomena are difficult to experimentally characterize due to inherent small spectral and temporal scales, and as such numerical and computational models are relied upon to inform fundamental physics. Experimental characterization of the behaviors of energetic materials during deformation is necessary to better inform computational studies and improve our understanding of hotspot formation mechanisms. </p> <p>This dissertation experimentally evaluates the high-rate deformation of porosity in individual explosive particulates and within the overall composite structure. This has included the development of a novel micromachining technique for pore generation in energetic single crystals using the focused ion beam (FIB), resulting in precise and controllable porosity generation that is easily reproducible in collaboration with computational studies. FIB was shown to be an effective pore generation technique, verified by assessing surface roughness and pore quality compared to contemporary manufacturing methods. Three experimental subsets are evaluated: surface cracks in HMX single crystals, polygonal pores in HMX single crystals, and large-scale porosity variations in mock vibration assisted print (VAP) produced composites of borosilicate glass beads and Sylgard 184® binder. A single stage light gas gun was used to impact the samples at 400 m/s and the impact event and resultant material response were observed in real time using x-ray phase contrast imaging (PCI). Machined surface cracks were shown to have negligible effect on the final fracture behaviors of HMX crystals. In polygonal pores fractures were shown to originate due to stress concentration during impact followed by otherwise expected brittle fracture behaviors. For wedge-like pores, the shockwave culminates on the front face of the pore and contributed to early fracture in some samples as well as a consistent open fracture opposite the impact along the shockwave direction in later stages of impact. For the blunt rectangular-like pores two differing behaviors were observed, wherein either the pore condensed and fracture at the pore was not seen during the impact event or large open fractures formed at the pore corners opposite the shockwave. The variance in response is attributed to the energy of fracture dissipating somewhere else in the material bulk, like the behaviors observed in the milled slot samples. Finally, additively manufactured PBX deformation behaviors were observed to be dominated by the collapse of the existing ordered porosity in the bulk which occurred at an increased rate relative to the bulk material compression. This resulted in a three-stage progression of deformation, consisting of a rapid collapse of large-scale ordered porosity, followed by the densification of the remaining features, and ultimately ending in compaction of the bulk as the impact projectile fully compressed the samples. Future work includes exploration of further FIB produced pore effects on dynamic fractures, evaluation of printed material deformation behaviors at additional rates, as well as application and evaluation of additional VAP printed material formulations.  </p>