Depuis la découverte des rayons X par Röntgen, l'imagerie radiographique utilise le contraste d'absorption. Cette technique est efficace uniquement si les objets à étudier sont suffisamment absorbants. C'est pour cela qu'on peut détecter une lésion osseuse avec une radiographie, mais pas une lésion ligamentaire.Toutefois, l'imagerie par contraste de phase peut permettre de surmonter cette limite. Depuis les années 2000, s'appuyant sur des travaux similaires existant en optique visible, les scientifiques des rayons X essayent de mettre au point des dispositifs sensibles au contraste de phase et compatibles avec des applications industrielles comme l'imagerie médicale ou le contrôle non-destructif. Néanmoins, les architectures classiques des interféromètres sont très difficiles à mettre en place dans les rayons X durs, et sont trop contraignantes pour être transférables vers l'industrie. C'est pourquoi des dispositifs utilisant des réseaux de diffraction ont été les plus développés. Ils ont permis d'obtenir les premières images de radiographie par contraste de phase sur des humains vivants.Mais les architectures proposées aujourd'hui utilisent plusieurs réseaux et son contraignantes pour les industriels. C'est pourquoi j'ai développé au cours de ma thèse un système n'utilisant qu'un unique réseau de phase. J'ai montré qu'un tel dispositif peut générer des interférogrammes achromatiques et invariants par propagation. Ce dispositif a permis d'effectuer des mesures de contraste de phase quantitatives sur un fossile biologique, ainsi que des mesures métrologiques sur des miroirs plans sensibles aux rayons X. / Since Röntgen discovered X-rays, X-ray imaging systems are based on absorption contrast. This technique is inefficient for weakly absorbing objects. As a result, X-ray standard radiography can detect bones lesions, but cannot detect ligament lesions.However, phase contrast imaging can overcome this limitation. Since the years 2000, relying on former works of opticians, X-ray scientists are developing phase sensitive devices compatible with industrial applications such as medical imaging or non destructive control.Standard architectures for interferometry are challenging to implement in the X-ray domain.This is the reason why grating based interferometers became the most promising devices to envision industrial applications. They provided the first x-ray phase contrast images of living human samples.Nevertheless, actual grating based architectures require the use of at least two gratings, and are challenging to adapt on an industrial product. So, the aim of my thesis was to develop a single phase grating interferometer. I demonstrated that such a device can provide achromatic and propagation invariant interference patterns. I used this interferometer to perform quantitative phase contrast imaging of a biological fossil sample and x-ray flat mirror metrology.

Cette thèse a été réalisée entre 2014 et 2017 en vue de la préparation d'une mission probatoire du projet Imageur de Fresnel permettant de réaliser des observations astronomiques dans le domaine ultraviolet (UV). Il s'agit d'un modèle de télescope spatial diffractif imaginé et développé principalement par Laurent Koechlin depuis 2004. Son optique primaire est une grille de Fresnel, optique très légère (de l'ordre du kilogramme) parfaitement adaptée pour servir à une mission d'observation spatiale de très grande envergure, utilisant le principe des réseaux zonés de Fresnel. Afin de prouver la faisabilité d'une mission probatoire sur la Station Spatiale Internationale (ISS) fonctionnant dans l'ultraviolet, l'instrument doit d'abord faire la preuve de ses performances au sol. Le premier objectif a donc été de concevoir un nouveau prototype sol adapté à l'observation dans l'ultraviolet. Cela a nécessité la définition d'une nouvelle configuration de l'ensemble du système imageur, ainsi que la réalisation de nouvelles optiques, et en particulier celle du correcteur du chromatisme induit par la grille d'un nouveau genre. Il s'agit d'un miroir de Fresnel blazé concave, qui a été réalisé pour la première fois avec succès. Le second a été de perfectionner le modèle de grille de Fresnel, afin d'en améliorer ses qualités de haut contraste en conservant sa résolution maximale. Cela s'est fait par la modification des barreaux de maintien des anneaux, ainsi que par l'application d'une apodisation adaptée à cette optique particulière. La nouvelle grille du prototype d'une largeur de 65 mm seulement, permet théoriquement d'atteindre une dynamique de 10^6 à 15 resels (éléments de résolution), probablement meilleure avec la grille qui sera utilisée pour la mission probatoire, et bien supérieure encore avec les grilles de grandes dimensions si un jour elles sont utilisées pour l'astrophysique UV. / This Ph.D. thesis work was made between 2014 and 2017, in order to prepare a probatory mission of the Fresnel Imager for astronomical observations in the ultraviolet (UV) domain. The Fresnel Imager is a concept of diffractive telescope created and developed mainly by Laurent Koechlin since 2004. Its primary optics is a Fresnel grid: a very light weight optics (in the range of kilograms) using the principle of Fresnel zone plates. Fresnel arrays are adapted to large apertures in space. In order to prove the feasibility of a probatory mission on the International Space Station (ISS), the instrument has first to prove its performances on the ground. The initial goal of my thesis was to conceive a new prototype adapted to UV. This required a new configuration of the entire imaging system, as well as the realization of new optics, particularly those correcting the chromatism induced by that new kind of diffractive imaging. This chromatic corrector is a concave blazed Fresnel mirror, which has been successfully realized for the first time. The second goal was to improve the design of the Fresnel grid, in order to enhance its high contrast performances while preserving its diffraction-limited resolution. This was obtained by modifying the setup which holds the rings in place, as well as by the application of an apodization adapted to this particular optics. The new Fresnel grid in the prototype is 65 mm x 65 mm only, but its point spread function reaches a dynamic range of 10^6 at 15 resels (resolution element) from center. This will be further improved when a slightly larger array planned for the probatory mission on the ISS. Later, space missions could feature Fresnel grids several meters in size, yielding diffraction-limited images in the UV.

This dissertation presents the development and use of a novel optical imaging system capable of monitoring changes in blood flow, oxygenated hemoglobin, deoxygenated hemoglobin, and absolute pO₂ in the brain. There are several imaging modalities capable of monitoring these parameters separately. Laser speckle contrast imaging (LSCI) and multi-spectral reflectance imaging (MSRI) have been used to monitor relative blood flow and hemoglobin changes respectively. Phosphorescence quenching, while not typically used for imaging, is capable of noninvasive measurements of pO₂. Combining these three techniques has led to the development of an imaging system that could ultimately lead to a better understanding of brain physiology. By combining techniques such as LSCI and MSRI, it becomes possible to estimate the cerebral metabolic rate of oxygen (CMRO₂), an important indicator of neuronal function. It is equally important to understand absolute pO₂ levels so that oxygen metabolism can be examined in context. Integrating phosphorescence quenching and a spatial light modulator into the imaging system allowed absolute pO₂ to be simultaneously measured in distinct regions. This new combined system was used to investigate pathophysiological conditions such as cortical spreading depression (CSD) and ischemia. The observed hemodynamic changes associated with these events were largely dictated by baseline oxygen levels and varied significantly in different regions. This finding highlighted the importance of having a system capable of monitoring hemodynamic changes and absolute pO₂ simultaneously while maintaining enough spatial resolution to distinguish the changes in different regions. It was found that animals with low baseline pO₂ were unable to deliver enough oxygen to the brain during events like CSD because of the high metabolic demand. In order for this technique to become more prevalent among researchers, it is essential to make it cost effective and simple to use. This was accomplished by replacing the expensive excitation sources with cheaper light emitting diodes (LEDs) and redesigning the software interface so that it was easier to control the entire device. The final system shows the potential to become a key tool for researchers studying the role of absolute pO₂ and other hemodynamic parameters during pathophysiological conditions such as CSD and ischemia. / text

Tendo em vista experimentos envolvendo o estudo da dinâmica de gases quânticos aprisionados, visando a simulação quântica de sistemas complexos, este trabalho discute a implementação e o estudo da técnica de imagem dispersiva, por contraste de fase, e a compara com o método de imagem por absorção óptica. A implementação da nova técnica foi feita em um regime não convencional de dessintonia, explorando a região proxima da ressonância atômica, onde se deve levar em conta o efeito da absorção, além da mudança de fase, do campo elétrico do laser de prova, após interagir com os átomos. Portanto, este trabalho apresenta não só a implementação de uma nova técnica experimental, mas também um modelo simples para interpretar os dados obtidos nesse novo regime. / Envisioning experiments involving the dynamics of trapped quantum gases, towards the quantum simulation of complex systems, this work presents the implementation and study of a dispersive imaging technique, by phase contrast, and compares it to absorption imaging. The implementation of this new technique in our laboratory was done in a non conventional range of detunings, exploring the region near atomic resonance, where absortion effecs need to be taken into account, in addition to the phase shift, introduced in the electric field of the probing laser, after interacting with the atoms. Therefore, this work presents not only the implementation of a new experimental technique, but also a simple model to interpret the dada obtained in this new regime.

Le vieillissement est un facteur de risque des maladies cardiovasculaires. Il est associé à des altérations fonctionnelles et structurelles du système vasculaire.Une étude approfondie du processus de vieillissement et le développement de systèmes d’imagerie et des traitements de données associés deviennent donc une priorité. Par l’analyse d’images de contraste par speckle laser (LSCI), l’objectif de cette thèse est d’étudier l’influence de l’âge sur la micro circulation.Pour ce faire, des données de LSCI ont été acquises sur l’avant-bras de sujets sains jeunes et âgés. A partir de modèles mathématiques, nous avons déterminé la vitesse des érythrocytes de la micro circulation chez les deux groupes de sujets. Par ailleurs, nous avons également mené une étude de la complexité de séries temporelles d’ LSCI s’appuyant sur des mesures d’entropie multi échelle. Nos résultats montrent que : 1) le groupe de sujets plus âgés présente des valeurs de vitesse des globules rouges significativement plus élevées que celles des sujets jeunes à l’hyperémie réactive post-occlusive; 2) les fluctuations des séries temporelles de LSCI dans le groupe des sujets jeunes ont une complexité supérieure à celles du groupe de sujets âgés. Ces modifications observées sur la micro circulation pourraient être attribuées à des modifications du système vasculaire dans son ensemble. La compréhension de ces altérations pourrait conduire à de nouvelles perspectives en matière de prévention et de traitement des pathologies liées à l’âge. / Aging is a primary risk factor for cardiovascular diseases. It is associated with functional and structural alterations in the vascular system. Therefore, a deep study of the aging process and the development of imaging systems and associated processing become of the utmost importance. By processing laser speckle contrast images (LSCI), this PhD work aims at studying the influence of age on microcirculation. In our work, LSCI data were acquired from the skin forearm of healthy subjects, subdivided into two age groups (younger and older). From mathematical models, we determined red blood cells velocity in microcirculation in the two groups of subjects. Moreover, we applied multiscale entropy-based algorithms to LSCI time series in order to study the complexity of microvascular signals. Our main findings are: 1) the older group has significantly higher velocity values than the younger group at post-occlusive reactive hyperaemia; 2) LSCI fluctuations in the younger group have significantly higher complexity than those of the older group. Age-related changes in skin microcirculation can be attributed to alterations in the vascular system as a whole. Understanding these changes in the microcirculatory system may give new insights for prevention and treatment of age-related diseases

Polarization-dependence provides a unique handle for extending the dimensionality of optical microscopy, with particular benefits in nonlinear optical imaging. Polarization-dependent second order nonlinear optical processes such as second harmonic generation (SHG) provide rich qualitative and quantitative information on local molecular orientation distribution. By bridging Mueller and Jones tensor, a theoretical framework was introduced to experimentally extend the application of polarization-dependent SHG microscopy measurements toward in vivo imaging, in which partial polarization or depolarization of the beam can complicate polarization analysis. In addition, polarization wavefront shaping was demonstrated to enable a new quantitative phase contrast imaging strategy for thin transparent samples. The axially-offset differential interference contrast microscopy (ADIC) was achieved as a combination of classic Zernike phase contrast and Nomarski differential interference contrast (DIC) methods. The fundamentally unique manner of this strategy also inspired rapid volumetric analysis in time dimension that is accessible for most existing microscopy systems. Finally, the dimensionality of high speed twophoton fluorescence imaging was extended to the spectral domain by spatial/spectral multiplexing, enabling beam scanning two photon fluorescence microscopy with 17 frames per second rate and over 2000 effective spectral data points.<br>

Imager une exo-terre à proximité d’une étoile est une tâche complexe : le signal de la planète est noyé dans le flux immense de l’étoile, très proche. Doivent donc être combinés :- de grands télescopes spatiaux segmentés. La segmentation du miroir primaire facilite le transport mais crée des erreurs liées à l’alignement.- un coronographe, permettant d’éteindre la lumière stellaire. - enfin, toute aberration optique crée un résidu lumineux nuisible dans l’image. La mesure et le contrôle des aberrations d’un système coronographique, notamment celles liées à la segmentation du télescope, sont donc primordiaux et constituent le sujet de ma thèse.Tout d’abord, j’ai développé PASTIS, un modèle simplifié du contraste d’un coronographe en présence d’une pupille segmentée, permettant d’analyser facilement les performances pour contraindre les aberrations optiques lors du design de l’instrument. PASTIS prend en compte les spécificités des instruments : structure de la pupille, aberrations optiques dues à la segmentation, coronographe. Je l’ai appliqué au télescope LUVOIR afin d’analyser les modes limitant le contraste et ainsi mieux répartir les contraintes sur les segments. Par la suite, j’ai travaillé sur l’analyse de front d’onde coronographique en présence d’un télescope segmenté sur le banc expérimental HiCAT avec une première démonstration de l’analyseur COFFEE permettant de reconstruire les erreurs de phasage avec une grande précision. Enfin, j’ai mené une analyse comparative des multiples méthodes de contrôle de front d’onde existantes et validé l’une d’elles (Dark Hole Non Linéaire) expérimentalement dans un cadre simplifié sur le banc MITHIC du LAM / Direct imaging of exo-Earths is extremely complex: the star is by far brighter and very close to the planet. Several tools have to be combined:- a giant primary mirror. For manufacturing and transportation reasons, we tend to use segmented mirrors, ie. mirrors made of smaller mirrors but that have to be well-aligned and stabilised.- a coronagraph, enabling to remove the starlight.- the smallest residual wavefront aberration into residual light that decreases the image quality. The measurement and control of the aberrations, including the ones due to the telescope segmentation, are crucial and consist in the topic of my thesis.First, I developed PASTIS, a model of the contrast of a coronagraphic system in presence of a segmented pupil, enabling to analyze the performance to set up constraints on the optical aberrations during the instrument design. PASTIS takes into account the specificities of high-contrast instruments: pupil structure, optical aberrations due to the segmentation, coronagraph. I applied it to the LUVOIR telescope to analyze the main modes limiting the contrast and therefore optimizing the repartition of the constraints on the segments. In parallel, I worked on the analysis of the coronagraphic wavefront in presence of a segmented telescope on the experimental testbed called HiCAT, with a first demonstration of the COFFEE sensor enabling to reconstruct phasing errors with a high precision.Eventually, I ran a comparative analysis of existing methods of wavefront control and experimentally validated one of them (Non Linear Dark Hole) in a simplified case on the MITHIC testbed at LAM

Cette thèse vise à investiguer des moyens d'optimiser les performances de l'imagerie à haut contraste dans l'optique et le proche infrarouge pour la détection d'exo-planètes. L'étude principale a été menée sur le contraste à faible séparation permettant l'imagerie d'exo-planètes dans leur zone habitable. Cette détection directe est rendue possible par le développement des futurs grands télescopes et de coronographes de plus en plus performants à faible séparation. L'approche retenue permet de créer une zone sombre à haut contraste grâce à la coronographie et au « wavefront shaping » (contrôle de l'amplitude et de la phase avec 2 miroirs déformables), mais qui est limité par les effets de propagation de Fresnel. Les résultats obtenus ont déterminé les limitations de configuration optique pour le « wavefront shaping ». Grâce à une approche semi-analytique soutenue par des simulations numériques et une approche Monte-Carlo, ces limitations ont été analysées et quantifiées pour extraire les configurations optimales. Les résultats ont été appliqués au banc SPEED dont l'objectif est d'optimiser et de tester le haut contraste à faible séparation. Une deuxième étude a été une contribution à une étude générale de stabilité, en traitant la stabilité temporelle comme un paramètre indispensable dans la conception en amont d'instrument haut contraste. Un travail préliminaire a été initié sur la stabilité des instruments de mesure eux-mêmes à travers l'étude thermique d'un système de métrologie. Enfin, un dernier volet a été une étude de simulation de performances d'un nouveau concept d'imagerie différentielle basé sur l'acquisition d'images réalisées avec différentes tailles de pupilles. / This thesis aims to optimize high-contrast imaging performance in visible and near infrared for exoplanet detection. The main study focuses on high-contrast at small separation, to image exoplanets in their habitable zone. This direct detection is achievable with the next Extremely Large Telescopes and with the development of coronagraph providing high performance at small separation. The approach adopted for this study creates a high-contrast region (a dark hole) with the combination of coronagraphy and wavefront shaping (wavefront control of both phase and amplitude with 2 deformable mirrors) but is limited by the Fresnel propagation of phase aberrations. The goal of this work is to define the wavefront shaping limitation in optical configuration (deformable mirrors location, component optical quality, beam diameter). A semi-analytic approach followed by a Monte-Carlo analysis of numerical end-to-end simulations is studied, resulting in the definition of the optimal configuration. Results are then applied to SPEED, a test bench to optimize and test high-contrast imaging at small separation with a segmented pupil. Another aspect of this thesis is a contribution to a stability study to treat the temporal stability as a crucial parameter in high-contrast imaging instrumentation, at the conception level. A preliminary work is initiated during the thesis to analyse the stability of the measuring instrument itself. A metrology tool and its thermal behaviour are thus studied. Finally, the last part of this thesis is a performance analysis of a new differential imaging technique, developed to improve high contrast with observations with different diaphragm sizes.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13119号 / 論医博第2132号 / 新制||医||1023(附属図書館) / (主査)教授 大森 孝一, 教授 斎藤 通紀, 教授 長船 健二 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Microcirculation is defined as the blood flow in the smallest blood vessels. Laser speckle contrast imaging (LSCI) is a full field imaging technique that provides instantaneous 2-D perfusion maps of illuminated tissues based on speckle contrast. Perimed’s Perfusion Speckle Imager (PSI) is a medical device developed at Perimed AB that exploits LSCI to measure tissue blood perfusion. In this thesis work, a robust Autofocus (AF) algorithm for PSI was implemented. AF is a procedure to drive PSI camera to reach the depth of focus and acquire sharp images, that relies only on signal processing. Therefore, several Blind image sharpness assessment (BISA) methods, to judge the degree of image sharpness, were compared to choose which BISA method to incorporate in the algorithm. An optimized focus scanning technique was implemented to more efficiently find the depth of focus. When working with LSCI, speckle is a source of noise that destroys image content. Experiments were performed to study laser speckle filtration: digital filters were employed to attenuate the speckle noise that corrupted details in the acquired images. Finally, two methods to perform AF were provided. These procedures were proven practically with LED images. However, with laser source image information is corrupted by speckle despite the application of digital filters and AF remains a real challenge. Moreover, important hardware limitations require to be overcome to make the technique real-time. Focus motor speed should be higher to acquire images at different focus positions faster which could benefit the speed of the AF procedure and speckle filtration.