Optical coherence tomography systems are used to image the retina in 3D to allow ophthalmologists diagnose ocular disease. These systems yield large data sets that are often labor-intensive to analyze and require significant expertise in order to draw conclusions, especially when used over time to monitor disease progression. Spectral Domain Optical Coherence Tomography (SD-OCT) instantly acquires depth profiles at a single location with a broadband source. These systems require mechanical scanning to generate two- or three-dimensional images. Instead of mechanically scanning, a beamlet array was used to permit multiple depth measurements on the retina with a single snapshot using a 3x 3 beamlet array. This multi-channel system was designed, assembled, and tested using a 1 x 2 beamlet lens array instead of a 3 x 3 beamlet array as a proof of concept prototype. The source was a superluminescent diode centered at 840nm with a 45nm bandwidth. Theoretical axial resolution was 6.92um and depth of focus was 3.45mm. Glass samples of varying thickness ranging from 0.18mm to 1.14mm were measured with the system to validate that correct depth profiles can be acquired for each channel. The results demonstrated the prototype system performed as expected, and is ready to be modified for in vivo applicability.

V první části se práce se zabývá rešerší metod a principů potřebných při registraci obrazu. Dále pak popisuje zobrazovací systémy očního pozadí jako jsou OCT, fundus kamera a SLO. Druhá část práce je zaměřena na praktickou realizaci programů pro registraci snímků z OCT, SLO a fundus kamery v programovém prostředí Matlab.

Increased near infrared (NIR) reflection, closely resembling the red edge found in leaves, has been known in frogs for many years. Whereas previously thought of as an isolated rarity, we have shown that it is likely far more prevalent than previously believed, occurring in multiple distinct family groups and world regions. To date, there are now 26 anuran species known to demonstrate increased NIR reflectance, from 12 different genera, 4 families, and 3 ecozones. The visible/NIR reflection spectra of each individual measured was found to be characteristic of its species; whether it was wild or captive bred; and its sex. A machine learning based classification system was demonstrated as a viable method of identifying these properties from a frog's reflection spectra alone. How this reflection spectra developed from a pre-metamorphosis froglet through to adult frog was tracked, with the gradual changes to the reflection spectra of both NIR reflective and other frogs identified as being most likely dominated by the reduction in epidermal melanophores, and the increasing number of dermal iridophores. A modified consumer camera was shown to be a viable method for rapid identification of increased NIR reflection in anurans, and was used to identify that salamanders also show variation in NIR reflection between ground dwelling and leaf sitting species. The overnight colour change in Hylomantis lemur was observed, and found to occur pre-emptively of the frog's future location; with the frogs regularly transitioning from pale green ‘daytime' colouration, to the dark brown ‘night time' colouration, while still on the green leaf surface before becoming active, and undertaking the reverse transition while still active, but shortly before returning to the leaf. It seems likely that this change is for protection from silhouetting whilst active. Optical coherence tomography images were taken of several species of frog, and found to be a viable method for non-invasive investigation of anuran skin structure, with structural differences observed between the two colourations of H. lemur. It was found that the most likely cause of the increased NIR reflection in frogs is a reduction in melanin, either by absence or substitution with pterorhodin. Although the true benefit to the frog is difficult to determine, it seems likely that cryptic thermoregulation plays a key role: the maintenance of body temperature for the purpose of camouflage from animals capable of far-infrared vision. This thesis demonstrates the legitimacy of several techniques and approaches for non-invasive study of anurans, but the ultimate scope of the project is fundamentally limited by the range of frogs available. Further insight is likely to arise from increasing this scope, applying these techniques to more frogs, from more species, in more regions, and the author wishes all future researchers the greatest success in this endeavour.

Parmi les diverses méthodes d’imagerie médicales, les méthodes d’imagerie optique connaissent depuis une vingtaine d’années un développement significatif. Parmi les techniques d’imagerie optique récemment mises en œuvre, la Tomographie Optique Cohérente Plein Champ – ou OCT Plein Champ – présente des caractéristiques remarquables, en particulier en termes de résolution et de simplicité instrumentale, permettant d’envisager son application au domaine du diagnostic du cancer. Cette thèse décrit la conception et la mise en œuvre de dispositifs d’OCT Plein Champ pour utilisation en contexte clinique, afin d’évaluer la performance de la technique pour le diagnostic peropératoire du cancer, en vue de son amélioration et optimisation. Dans cet objectif nous avons réalisé des travaux regroupés en 2 axes : Une partie translationnelle, consistant à développer un dispositif de microscopie optique par OCT Plein Champ répondant au besoin clinique pour le diagnostic peropératoire du cancer sur biopsies, en vue de l’évaluation de ses performances de diagnostic sur plusieurs problématiques cliniques : le diagnostic peropératoire du tissu mammaire, de résection de cerveau, ainsi que la qualification préopératoire de greffons cornéens. Une partie exploratoire, principalement instrumentale, dédiée à l’amélioration des performances de diagnostic de la technique, proposant de nouvelles approches multimodales (contraste de fluorescence, contraste dynamique) et multi-échelles, ou encore la déclinaison du dispositif sous la forme d’un endoscope rigide portable utilisable en contexte clinique. / Among medical imaging techniques, optical imaging methods have been significantly developped during the past decades. More specifically, among recently proposed optical imaging techniques, Full-Field Optical Coherence Tomography – or FFOCT – provides unique capabilities, in particular regarding resolution and instrumental simplicity, which allows to consider its application to cancer diagnosis. This thesis demonstrates the design and implementation of new FFOCT devices for use in a clinical context, targeting improvement and optimization of the technique. Two major development parts have been realized : A translational part, comprising the development of a FFOCT microscope adapted to a clinical use for intraoperative diagnosis of cancer on tissue biopsies, and the assessment of its diagnosis performance for several clinical cases : the intraoperative diagnosis of breast tissue, of brain resections, and the preoperative qualification of corneal grafts. A research part - mainly instrumental - targeting the improvement of the diagnosis performance of the technique, based on new multimodal (fluorescence contrast, dynamic contrast) and multiscale approaches, or on the miniaturization of the device by developing a handheld rigid endoscope for clinical use.

Optical Coherence Tomography (OCT) is a noninvasive imaging modality that has significantly contributed to the quantitative assessment of ocular diseases. Another tool available to ophthalmic clinicians is in-vivo confocal microscopy, which allows anatomical structures to be observed live at the cellular level. Incorporating both of these modalities for imaging the cornea allows us to take structural measurements to characterize disease-related changes in corneal anatomy. Notable diseases that directly impact or correlate with corneal structures include glaucoma and diabetic neuropathy. Given glaucoma's impact as the second leading cause of blindness in the world, great efforts have been made in researching and understanding the disease. Correlations have been found between the central corneal thickness (CCT) and the risk of developing visual field loss in patients diagnosed with glaucoma. It should come as no surprise that measuring CCT among glaucoma suspects has also now become a clinical standard of practice. Diabetes is a group of metabolic diseases where the body experiences high blood sugar levels over prolonged periods of time. It is a prominent disease that affects millions of Americans each day. While not necessarily an ocular disease in its own right, it has been shown that diabetes can still affect the corneal structures. Diabetics have decreased corneal sensitivity and a significant link has been established between neuropathic severity in diabetic patients and corneal nerve fiber density. Given the availability of these imaging tools and the significant impact these prominent diseases have on society a growing focus has developed on relating corneal structure measurements and ophthalmic diseases. However, manually acquiring structural measures of the cornea can be a labor intensive and daunting task. Hence, experts have sought to develop automatic alternatives. The goals of our work includes the ability to automatically segment the corneal structures from anterior segment-optical coherence tomography (AS-OCT) and in-vivo confocal microscopy (IVCM) to provide useful structural information from the cornea. The major contributions of this work include 1) utilizing the information of AS-OCT imagery to segment the cornea layers simultaneously in 3D, 2) increasing the region-of-interest of IVCM imagery using a feature-based registration approach to develop a panorama from the images, 3) incorporating machine-learning techniques to segment the corneal nerves in the IVCM imagery, and 4) extracting structural measurements from the segmentation results to determine correlations between the structural measurements known to differ from the corneal structures in various subject groups.

The task of automatically segmenting 3-D surfaces representing object boundaries is important in quantitative analysis of volumetric images, which plays a vital role in numerous biomedical applications. For the diagnosis and management of disease, segmentation of images of organs and tissues is a crucial step for the quantification of medical images. Segmentation finds the boundaries or, limited to the 3-D case, the surfaces, that separate regions, tissues or areas of an image, and it is essential that these boundaries approximate the true boundary, typically by human experts, as closely as possible. Recently, graph-based methods with a global optimization property have been studied and used for various applications. Sepecifically, the state-of-the-art graph search (optimal surface segmentation) method has been successfully used for various such biomedical applications. Despite their widespread use for image segmentation, real world medical image segmentation problems often pose difficult challenges, wherein graph based segmentation methods in its purest form may not be able to perform the segmentation task successfully. This doctoral work has a twofold objective. 1)To identify medical image segmentation problems which are difficult to solve using existing graph based method and develop novel methods by employing graph search as a building block to improve segmentation accuracy and efficiency. 2) To develop a novel multiple surface segmentation strategy using deep learning which is more computationally efficient and generic than the exisiting graph based methods, while eliminating the need for human expert intervention as required in the current surface segmentation methods. This developed method is possibly the first of its kind where the method does not require and human expert designed operations. To accomplish the objectives of this thesis work, a comprehensive framework of graph based and deep learning methods is proposed to achieve the goal by successfully fulfilling the follwoing three aims. First, an efficient, automated and accurate graph based method is developed to segment surfaces which have steep change in surface profiles and abrupt distance changes between two adjacent surfaces. The developed method is applied and validated on intra-retinal layer segmentation of Spectral Domain Optical Coherence Tomograph (SD-OCT) images of eye with Glaucoma, Age Related Macular Degneration and Pigment Epithelium Detachment. Second, a globally optimal graph based method is developed to attain subvoxel and super resolution accuracy for multiple surface segmentation problem while imposing convex constraints. The developed method was applied to layer segmentation of SD-OCT images of normal eye and vessel walls in Intravascular Ultrasound (IVUS) images. Third, a deep learning based multiple surface segmentation is developed which is more generic, computaionally effieient and eliminates the requirement of human expert interventions (like transformation designs, feature extrraction, parameter tuning, constraint modelling etc.) required by existing surface segmentation methods in varying capacities. The developed method was applied to SD-OCT images of normal and diseased eyes, to validate the superior segmentaion performance, computation efficieny and the generic nature of the framework, compared to the state-of-the-art graph search method.

Cette thèse propose une nouvelle méthode de détection, intermédiaire entre les deux méthodes existantes en OCT, qui sont: l'OCT dans le domaine temporel et l'OCT dans le domaine fréquentiel (FDOCT). La technique OCT que nous présentons est basée sur un réseau de diffraction. Elle fournit le profil de réflectivité en profondeur de l'échantillon analysé instantanément, sans effectuer de balayage mécanique dans le bras de référence de l'interféromètre ni de traitement numérique du signal réfléchi par l'échantillon. Une partie de cette thèse est dédiée à la description du principe de fonctionnement et à l'architecture du dispositif. En introduisant un balayage transversal dans le système, des images en deux dimensions et en trois dimensions de l'échantillon ont été réalisées. Nous décrivons par la suite comment nous accédons à l'information spectroscopique en profondeur de l'échantillon analysé, de façon optique et sans post-traitement grâce à la même technique. Pour cela, un système de démultiplexage en longueur d'onde est introduit dans le dispositif OCT qui devient ainsi un instrument de spectro-tomographie optique de cohérence. De cette façon, pour chaque point objet analysé, une image en deux dimensions est affichée en temps réel sur un détecteur plan. La direction horizontale correspond à la profondeur tandis que la direction verticale correspond à la décomposition spectrale de la trace de corrélation. Nous présentons le principe du système et montrons quelques résultats expérimentaux.

On New Year's Eve 1993, there was little indication that popular President Carlos Salinas de Gortari was about to take a monumental fall. Mexico was in the midst of unprecedented prosperity. The world's oldest ruling political party, Mexico's PRI, enjoyed substantial support. Allegations of corruption within an authoritarian regime were now frivolous charges obscured by economic success. The nation was poised to become a major player in the global market; vying with Japan to be the second largest trading partner of the U.S.A. The North American Free Trade Agreement (NAFTA) between Canada, the largest trading partner of the U.S., Mexico and the United States became effective January 1, 1994. Just after midnight 1994, the Zapatista National Liberation Army (EZLN) went to war in the southern Mexican state of Chiapas. Approximately 2500 peasants (mostly indigenous men of Mayan descent) had mobilized against the Mexican government. The violence sparked world wide interest in the human rights of Mexican Indians. Ten days later, as the EZLN retreated into the jungle, an international audience remained captivated by the struggle. The Mexican Army did not advance. The EZLN refused to lay down its arms. Within the year, the Mexican economy collapsed. Soon thereafter, President Salinas went into voluntary exile amidst charges of high crimes against the state. Was it just a coincidence that the rebellion coincided with the implementation of NAFTA? Did the treaty really present such an enormous threat to Mexico's underclass? Did NAFTA contribute to the nation's political problems? The following thesis answers these questions. It is the product of years of travel and study throughout Chiapas and Mexico, both before and after the rebellion. The intricacies of the relationship between NAFTA, the Mexican government and the EZLN are revealed. The government's position and rebel demands are reconcilable. This is an important conclusion. But Mexico is a poor country embroiled in a rebellion to the south as well as a precarious economic treaty with the world's wealthiest nation to the north. In addition, the EZLN has come to represent the world's beleaguered poor in an era of free trade. As Mexico's past and present are explored, conclusions about the country's future have implications that go beyond NAFTA. / Graduation date: 2000

The human crystalline lens is a complex, inhomogeneous and dynamic optical element which enables the eye to adjust focus in a process known as accommodation. Age related changes in the optical and mechanical properties of the lens cause a loss in accommodative ability leading to a condition known as presbyopia. Several experimental surgical techniques are under development for the correction of presbyopia. The goal of this dissertation is to better understand the relationship between the crystalline lens shape, its non-uniform refractive index gradient and its optical power and their changes with age and accommodation. In this study direct lens power and shape measurements were acquired on isolated lenses, and on lenses mounted in a lens stretching system designed to simulate accommodation. Several lens shape and power measurement techniques were developed for this study including a Scheimpflug camera system optimized for imaging the crystalline lens. Direct measurements of lens shape and power were used to develop an age-dependent optical-mechanical model of the lens during accommodation. The study shows that the normal growth of the lens is a major contributor to the progressive loss of accommodation amplitude, independent of changes in the elastic properties of the lens. These findings suggest that accommodation can be restored by refilling the lens with a material having a uniform refractive index.

Micro-Electro-Mechanical Systems (MEMS) micromirrors have been developed for more than two decades along with the development of MEMS technology. They have been used into many application fields: optical switches, digital light projector (DLP), adoptive optics (AO), high definition (HD) display, barcode reader, endoscopic optical coherence tomography (OCT) and confocal microscope, and so on. Especially, MEMS mirrors applied into endoscopic OCT and confocal microscope are the intensive research field. Various actuation mechanisms, such as electrostatic, electromagnetic, electro bimorph thermal, electrowetting, piezoelectric (PZT) and hybrid actuators, are adopted by different types of micromirrors. Among these actuators, the electrostatic is easily understood and simple to realize, therefore, it is broadly adopted by a large number of micromirrors. This thesis reports the design, fabrication, and characterization of a 2-D Silicon-on-insulation (SOI) MEMS micromirror with sidewall (SW) electrodes for endoscopic OCT or confocal microscope imaging. The biaxial MEMS mirror with SW electrodes is actuated by electrostatic actuators. The dimension of mirror plate is 1000micron×1000micron, with a thickness of a 35micron. The analytical modeling of SW electrodes, fabrication process, and performance characteristics are described. In comparison to traditional electrostatic actuators, parallel-plate and comb-drive, SW electrodes combined with bottom electrodes achieve a large tilt angle under a low drive voltage that the comb-drive does and possess fairly simple fabrication process same as that of the parallel-plate. A new fabrication process based on SOI wafer, hybrid bulk/surface micromachined technology, and a high-aspect-ratio shadow mask is presented. Moreover, the fabrication process is successfully extended to fabricate 2×2 and 4×4 micromirror arrays. Finally, a biaxial MEMS mirror with SW electrodes was used into Confocal MACROscope for imaging. Studied optical requirements in terms of two optical configurations and frequency optimization of the micromirror, the biaxial MEMS mirror replaces the galvo-scanner and improves the MACROscope. Meanwhile, a new Micromirror-based Laser Scanning Microscope system is presented and allows 2D images to be acquired and displayed.