O propósito deste trabalho tem sido a utilização das técnicas de Desenho Óptico para o desenvolvimento de sistemas ópticos altamente otimizados. Após a confeccção destes sistemas ópticos torna-se necessário avaliar o desempenho do sistema construído, para isto tem sido utilizado uma das técnicas mais modernas para avaliação de qualidade da imagem óptica, a função de transferência óptica FTO, mais especificamente a função de transferência de modulação FTM. FTM representa o módulo da função complexa FTO e está associada à medida direta e quantitativa da qualidade de imagem, descrevendo a estrutura da imagem como uma função da freqüência espacial. Estas duas técnicas são as ferramentas fundamentais para os desenhistas ópticos. Instrumentos oftálmicos como o microscópio cirúrgico, sistema óptico para adaptação de uma câmera CCD e a lâmpada de fenda são desenvolvidos e analisados por estas técnicas neste trabalho. / The purpose of this work has been the use of design optical techniques to development of highly optimized optical systems. After the fabrication of these systems, it is necessary to evaluate the performance of building systems. A modern technique used to evaluate the quality of optical image is the optical transfer function OTF, more exactly the modulation transfer function MTF. MTF is the modulus of the complex function OTF. MTF is associated the direct and quantitative measure of the image quality and it describes the image structure as a function of spatial frequency. This bides techniques are the tools of optical designers. Ophthalmic instruments like surgery microscope, optical system of CCD camera adaptation and slit lamps are developed and analyzed for this techniques in this work.

Nous avons développé un microscope tomographique diffractif en réflexion, qui permet d’observer la surface d’un échantillon avec une résolution latérale améliorée comparée à un microscope holographique conventionnel. À partir des même données expérimentales (les hologrammes acquis sous différents angles d’illumination), des mesures à haute précision longitudinale peuvent être réalisées sur la surface d’un échantillon purement réfléchissant, par reconstruction du profil de hauteur à partir de la phase. Cette méthode d’imagerie multimodale présente plusieurs avantages comparée aux mesures en holographie interférométrique classique : amélioration de la résolution latérale sur la partie diffractive, déroulement de phase facilité, réduction du bruit cohérent, l’ensemble étant associé à la grande précision longitudinale fournie par les mesures de phase. Nous montrons ces possibilités en imageant divers échantillons minces. / We have developed a tomographic diffractive microscope in reflection, which permits observation of sample surfaces with an improved lateral resolution, compared to a conventional holographic microscope. From the same set of data, high-precision measurements can be performed on the shape of the reflective surface by reconstructing the phase of the diffracted field. doing so allows for several advantages compared to classical holographic interferometric measurements: improvement in lateral resolution, easier phase unwrapping, reduction of the coherent noise, combined with the high-longitudinal precision provided by interferometric phase measurements. We demonstrate these capabilities by imaging various test samples.

Le principal but de cette thèse est d'adapter une méthode basée sur le retournement temporel, la méthode DORT (Décomposition de l'opérateur Retournement Temporel), a l'imagerie médicale. La plupart des résultats concernent aussi d'autres domaines de l'imagerie acoustique. En effet, l'échographie médicale a subi un important développement, mais reste limite chez certains patients par le fait que les tissus sont inhomogènes. La focalisation, et donc la qualité de l'image sont fortement dégrades par la traversée de milieu inhomogènes. Pour corriger ce problème et obtenir une bonne focalisation, il est nécessaire d'estimer les fonctions de Green de points du milieu. Nous proposons une approche par retournement temporel. Nous étendons la théorie de la méthode DORT au mode d'acquisition échographique, et introduisons le model de transducteurs virtuels qui permet de traiter le problème facilement. Ensuite, nous étendons la méthode aux signaux aléatoire (speckle) qui sont les signaux majoritaires en imagerie médicale, et en proposons une interprétation statistique basée sur le théorème de Van Cittert Zernike. L'étude des objets étendus est aussi faite. Finalement, échographie médicale utilise des signaux larges bandes, alors que la méthode DORT est principalement une méthode monochromatique. Des méthodes permettant d'obtenir les fonctions de Green temporelles sont développes dans le chapitre 5. En particulier, nous présentons la décomposition de Opérateur Retournement Temporel dans le domaine temporel, ce qui fait intervenir un tenseur d'ordre 4.

La croissance de la complexité des Circuits Intégrés (CI) conduit à rechercher de nouveaux outils pour la mise au point de CI prototypes. La possibilité de «voir travailler» un circuit en utilisant un Microscopie Electronique à Balayage (MEB) exploité en mode de contraste de potentiel semble être une (la) solution possible. Ce contexte permet en effet de relever les états logiques et électriques au niveau des composants internes (transistors). Les zones à analyser sont choisies par le concepteur, soit sur l'image observée soit à partir de sa description issue des outils de CAO. Dans ce cadre sont présentés ici: le contexte des travaux: l'outil d'Analyse des CI par Microscopie Electronique; l'étude des déformations géométriques et optiques des images obtenues; une proposition de solution en vue de permettre une corrélation entre l'image des circuits et leur description

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

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The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) both belong to the group of mature B-cell malignancies. However, MCL is typically clinically aggressive while the clinical course of CLL varies. CLL can be divided into prognostic subgroups based on IGHV mutational status and into multiple subsets based on closely homologous (stereotyped) B-cell receptors. In paper I we investigated 31 MCL cases using high-density 250K single-nucleotide polymorphism arrays and gene expression arrays. Although most copy-number aberrations (CNAs) were previously reported in MCL, a novel deletion was identified at 20q (16%) containing the candidate tumor suppressor gene ZFP64. A high proliferation gene expression signature was associated with poor prognosis, large CNAs, 7p gains and 9q losses. Losses at 1p/8p/13q/17p were associated with increased genomic complexity. In paper II we sequenced exons 4 to 8 of the TP53 gene in 119 MCL cases. 17p copy-number status was known from previous studies or determined by real-time quantitative polymerase chain reaction. TP53 mutations were detected in 14% of cases and were strongly associated with poor survival while 17p deletions were more common (32%) but did not predict survival. In papers III and IV we applied high-resolution genomic 27K methylation arrays to 20 MCL and 39 CLL samples. In paper III MCL displayed a homogenous methylation profile without correlation with the proliferation signature whereas MCL was clearly separated from CLL. Gene ontology analysis revealed enrichment of developmental genes, in particular homeobox transcription factor genes, among targets methylated in MCL. In paper IV we compared three different stereotyped CLL subsets: #1 (IGHV unmutated), #2 (IGHV3-21) and #4 (IGHV mutated). Many genes were differentially methylated between each two subsets and immune response genes (e.g. CD80 and CD86) were enriched among genes methylated in subset #1 but not in subsets #2/#4. In summary, CNAs were frequent and not random in MCL. Specific CNAs correlated with a high proliferation gene expression signature or genomic complexity. TP53 mutations predicted short survival whereas 17p deletions did not. A high proliferation signature was not associated with differential DNA methylation in MCL, which demonstrated a homogeneous methylation pattern. In contrast, genomic methylation patterns differed between MCL and CLL and between stereotyped CLL subsets.

This work builds up on the greatest minds of Cambridge Holography: Adrian Cable, Edward Buckley, Jonathan Freeman, and Christoph Bay. Cable and Buckley, developed an OSPR algorithm which was the first to provide high-quality real-time hologram generation using general-purpose hardware while Freeman designed a method to correct arbitrary aberrations. As ingenious as the method was, the calculations were extensively lengthy. Addressing this issue, a variant of OSPR suited for correcting spatially-varying aberration is presented. The algorithm combines the approaches of Cable, Buckley and Freeman to provide real-time hologram generation while incorporating various corrections (aberration, distortion, and pixel shape envelope). A high-performance implementation on a mid-range GPU achieved hologram generation up to 12 fps. Following topic studied is an adaptive optical correction. This work attempts to construct a set of methods, forming an automated testbed for holographic projectors. Each model, after exiting the production line is placed on such testbed, having all of its imperfections characterized. Once calibrated, each model is able to display highest-quality image throughout its life-span. An application of this work to industry was carried in collaboration with Dr Phillip Hands (University of Edinburgh) and LumeJET. Three demonstrators are constructed intending for a cost-effective system for holographic lithography. They are characterized using the developed testbed. Using the supersampled Adaptive OSPR algorithm, the diffraction limit was surpassed 2.75 times allowing to increase the patterning area. This combines approaches of Cable, Buckley, Freeman and Bay to achieve a wide field-of-view and high pixel-count replay field using off-the-shelf components. This thesis is finished describing the work on 3D holography carried with Penteract28. It is shown that the 2D hologram in the presence of spatially-varying aberrations is mathematically equivalent to a 3D hologram. The same implementation of the algorithm can be used to provide real-time 3D hologram generation.