O principal intento deste trabalho é demonstrar como a combinação de resultados de modelos radiométricos e de análises do limite de resolução de imagens produzem impactos positivos não apenas no projeto óptico de retinógrafos de alta resolução, mas que também geram ferramentas que auxiliam na definição da arquitetura de todo o equipamento, considerando, inclusive, os limites impostos por normas internacionais para a segurança do paciente em relação a radiação emitida na realização dos exames. Particularmente ao projeto óptico, foram desenvolvidos os sistemas de iluminação e imageamento da retina, onde se destacam duas propostas de metodologias: a primeira para a implementação da técnica de eliminação das bem conhecidas retro-reflexões geradas no conjunto óptico que é comum à iluminação e ao imageamento da retina, e a segunda para a obtenção de soluções efetivas em sistemas imageadores, que prima pela diminuição da sensibilidade dos componentes aos erros que são introduzidos pelos processos de fabricação e montagem. Analisando os resultados obtidos com o protótipo, foram validados os sistemas e modelos propostos, que se tornaram parte integrante de um produto oftalmológico aprovado para a comercialização, o retinógrafo Kiron. / The fundamental objective of this work is to demonstrate how radiometric models and analysis of the limit of resolution can provide not only positive impacts to the optical project of high resolution fundus cameras, but also creates tools to perform an optimization of all the equipment, considering the limits imposed by international standards to ensure security to the patient regarding the equipment radiation emission. In the optical project in particular, the imaging and illuminating systems of the retina were developed, in which stands out two proposed methodologies: first, to eliminate the well known retro-reflections in the common optical assembly of the imaging and illuminating systems, and a second one that helps the optical designer to find effective solutions in imaging systems, focused in the reduction of the component sensitivity to the fabrication and assembly processes errors. Analyzing the results from the prototypes the systems and the models proposed were validated, becoming integrant part of an ophthalmic product approved for commercialization, the Kiron fundus camera.

The goal of this thesis is to design and implement a program capable of automatically generating synthetic images of eye retinas. The generated images should be similar to those of real retinas, which are hard to obtain, so they could be used for development of various algorithms, which work with eye retina images in their place. This thesis describes anatomic properties of the eye retina, ways to take images of it and also usage of eye retina recognition in biometric and medicinal applications. Design of the program and the way in which individual parts of the retina are assembled together into the final image is also explained in this thesis. These individual parts are created using procedural textures in separate layers of the image. Next chapter of this work describes implementation details of the program. The conclusion then experimentally verifies suitability of the generated images for algorithmic processing.

Segmentation of the vasculature is an important step in the process of the retinal image analysis.Theresultsoftheanalysiscanbeusedtodiagnoseseveraleyeandcardiovascular diseases. The aim of this thesis is to search for possibilities in video-sequences from experimental fundus camera.

Segmentation of the vasculature is an important step in the process of the retinal image analysis.Theresultsoftheanalysiscanbeusedtodiagnoseseveraleyeandcardiovascular diseases. The aim of this thesis is to search for possibilities in video-sequences from experimental fundus camera.

Final publication is available at http://www.nature.com/articles/srep12283 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19559号 / 医博第4066号 / 新制||医||1013(附属図書館) / 32595 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 小池 薫, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Produits principalement entre le IIe s. av. et le Ier s. ap. J.-C., les écrits agronomiques latins, de Caton à Pline l'Ancien, permettent d'évaluer et de comprendre les contraintes naturelles et sociales qui ont déterminé, de façon évolutive, un modèle d'organisation et de gestion du domaine agropastoral. Formes de raisonnement et caractéristiques de composition et d'énonciation participent d'un effort de codification de la science agronimique et de ses objets. Tout en impliquant une représentation idéale des paysages du fundus, les normes agronomiques romaines sont édictées de façon de plus en plus souple pour intégrer la pluralité et la diversité des situations agraires que rencontre Rome au fur et à mesure de son expansion. Une analyse de fréquence des thèmes relatifs aux paysages fait apparaître les critères majeurs d'appréciation de l'environnement qui retiennent l'attention des experts agronomiques dans la perspective d'une exploitation et d'un aménagement, raisonnés et rentables, de l'espace rural. Ces normes agronomiques sont également soutenues par des considérations d'ordre idéologique. Illustrées par l'utilisation de symboles et d'images, les valeurs prônées, issues de l'ornamentum nobiliaire, viennent justifier les principes d'ordre et de mesure qui dovent présider à l'organisation spatiale et humaine des fundi ruraux.

A análise da retina permite o diagnostico de muitas patologias relacionadas ao olho humano. A qualidade da imagem e um fator importante já que o médico normalmente examina os pequenos vasos da retina e a sua coloração. O equipamento normalmente utilizado para a visualização da retina e o retinógrafo digital, que utiliza sensor colorido com filtro de Bayer e luz (flash) branca. No entanto, esse filtro causa perda na resolução espacial, uma vez que e necessário um processo de interpolação matemática para a formação da imagem. Com o objetivo de melhorar a qualidade da imagem da retina, um retinógrafo com câmera CCD monocromática de alta resolução foi desenvolvido. Nele, as imagens coloridas são geradas pela combinação dos canais monocromáticos R (vermelho), G (verde) e B (azul), adquiridos com o chaveamento da iluminação do olho com LED vermelho, verde e azul, respectivamente. Entretanto, o pequeno período entre os flashes pode causar desalinhamento entre os canais devido a pequenos movimentos do olho. Assim, este trabalho apresenta uma técnica de registro de imagens, baseado em correlação de fase no domínio da frequência, para realizar precisamente o alinhamento dos canais RGB no processo de geração de imagens coloridas da retina. A validação do método foi realizada com um olho mecânico (phantom) para a geração de 50 imagens desalinhadas que foram corrigidas pelo método proposto e comparadas com as imagens alinhadas obtidas como referência (ground-truth). Os resultados mostraram que retinógrafo com câmera monocromática e o método de registro proposto nesse trabalho podem produzir imagens coloridas da retina com alta resolução espacial, sem a perda de qualidade intrínseca às câmeras CCD coloridas que utilizam o filtro de Bayer. / The analysis of retina allows the diagnostics of several pathologies related to the human eye. Image quality is an important factor since the physician often examines the small vessels of the retina and its color. The device usually used to observe the retina is the fundus camera, which uses color sensor with Bayer filter and white light. However, this filter causes loss of spatial resolution, since it is necessary a mathematical interpolation process to create the final image. Aiming at improving the retina image quality, a fundus camera with monochromatic CCD camera was developed. In this device, color images are generated by combining the monochromatic channels R (red), G (green) and B (blue), which were acquired by switching the eye illumination with red, green and blue light, respectively. However, the short period between the flashes may cause misalignment among the channels because of the small movements of the eye. Thus, this work presents an image registration technique based on phase correlation in the frequency domain, for accurately aligning the RGB channels on the process of generating retina color images. Validation of the method was performed by using a mechanical eye (phantom) for generating 50 misaligned images, which were aligned by the proposed method and compared to the aligned images obtained as references (ground-truth). Results showed that the fundus camera with monochromatic camera and the method proposed in this work can produce high spatial resolution images without the loss of quality intrinsic to color CCD cameras that uses Bayer filter.

Currently available methods for managing glaucoma, e.g. the planimetry on stereo disc photographs, involve a subjective component either by the patient or examiner. In addition, a few structures may overlap together on the essential 2-D images, which can decrease reproducibility. Spectral domain optical coherence tomography (SD-OCT) provides a 3-D, cross-sectional, microscale depiction of biological tissues. Given the wealth of volumetric information at microscale resolution available with SD-OCT, it is likely that better parameters can be obtained for measuring glaucoma changes that move beyond what is possible using fundus photography etc. The neural canal opening (NCO) is a 3-D single anatomic structure in SD-OCT volumes. It is proposed as a basis for a stable reference plane from which various optic nerve morphometric parameters can be derived. The overall aim of this Ph.D. project is to develop a framework to segment the 3-D NCO and its related structure retinal vessels using information from SD-OCT volumes and/or fundus photographs to aid the management of glaucoma changes. Based on the mutual positional relationship of the NCO and vessels, a multimodal 3-D scale-learning-based framework is developed to iteratively identify them in SD-OCT volumes by incorporating each other's pre-identified positional information. The algorithm first applies a 3-D wavelet-transform-learning-based layer segmentation and pre-segments the NCO using graph search. To aid a better NCO detection, the vessels are identified either using a SD-OCT segmentation approach incorporating the presegmented NCO positional information to the vessel classification or a multimodal approach combining the complementary features from SD-OCT volumes and fundus photographs (or a registered-fundus approach based on the original fundus vessel segmentation). The obtained vessel positional information is then used to help enhance the NCO segmentation by incorporating that to the cost function of graph search. Note that the 3-D wavelet transform via lifting scheme has been used to remove high frequency noises and extract texture properties in SD-OCT volumes etc. The graph search has been used for finding the optimal solution of 3-D multiple surfaces using edge and additionally regional information. In this work, the use of the 3-D wavelet-transform-learning-based cost function for the graph search is a further extension of the 3-D wavelet transform and graph search. The major contributions of this work include: 1) extending the 3-D graph theoretic segmentation to the use of 3-D scale-learning-based cost function, 2) developing a graph theoretic approach for segmenting the NCO in SD-OCT volumes, 3) developing a 3-D wavelet-transform-learning-based graph theoretic approach for segmenting the NCO in SD-OCT volumes by iteratively utilizing the pre-identified NCO and vessel positional information (from 4 or 5), 4) developing a vessel classification approach in SD-OCT volumes by incorporating the pre-segmented NCO positional information to the vessel classification to suppress the NCO false positives, and 5) developing a multimodal concurrent classification and a registered-fundus approach for better identifying vessels in SD-OCT volumes using additional fundus information.

A case-control study was performed to evaluate the Swedish population-based symphysis fundus (SF) reference curves. The study included 242 small for gestational age (SGA) neonates (169 term and 73 preterm infants) as cases and 296 non-SGA infants as controls. Two Swedish SF curves were evaluated. In term pregnancies they showed a sensitivity of 32 % and 51 % and a specificity of 90 % and 83 %, respectively, at a cut-off level of < - 2 SD from the mean according to the SF reference curve. The sensitivity for SGA was higher in preterm pregnancies (49 % and 58 %, respectively) and the first alarm below – 2 SD was noted before 32 weeks in 37 % and 43 % of the preterm pregnancies, respectively. (Study I) A study of self-administered SF measurements was designed to achieve more regular and frequent SF measurements. Thirty-three women with singleton, ultrasound dated pregnancies performed SF measurements on average 14 weeks from gestational week 20 to 25 until delivery. Self-administered SF measurements were higher and had higher variance than midwives’ measurements. Four consecutive SF measurements on each occasion can compensate for higher variance. Reliable self-administered SF measurements can be obtained. (Study II) Self-administered SF measurements from 191 women were used to construct absolute and relative SF growth references. The influence of fetal sex, maternal obesity and parity was assessed in regression models. The lnSF growth was statistically influenced by maternal obesity, and a borderline significance was recorded for fetal sex and parity. Statistical analysis and graphical displays show no evidence that the relative lnSF growth should be dependent on these variables. (Study III) To improve detection of infants with intrauterine growth restriction (IUGR) rather than SGA a new statistical model (the SR method) was used. The SR method was evaluated with SF measurements from 1122 pregnant women. The sensitivity for neonatal morbidity and SGA was low, between 6 and 36 % for SGA (< -2SD). Neonates classified as SGA (< -2SD and < 10th percentile) had increased morbidity compared with the total study group. Neonates suspected to be SGA before delivery by the population-based SF measurement method had lower morbidity than those not suspected. The SR method was found not to improve detection of fetuses with increased morbidity or SGA neonates in this study. Better screening methods to detect IUGR and SGA prior to delivery are needed. (Study IV)

In this Ph.D. thesis, we study new methods to analyse digital fundus images of diabetic patients. In particular, we concentrate on the development of the algorithmic components of an automatic screening system for diabetic retinopathy. The techniques developed can be categorized in: quality assessment and improvement, lesion segmentation and diagnosis. For the first category, we present a fast algorithm to numerically estimate the quality of a single image by employing vasculature and colour-based features; additionally, we show how it is possible to increase the image quality and remove reflection artefacts by merging information gathered in multiple fundus images (which are captured by changing the stare point of the patient). For the second category, two families of lesion are targeted: exudate and microaneurysms; two new algorithms which work on single fundus images are proposed and compared with existing techniques in order to prove their efficacy; in the microaneurysms case, a new Radon transform-based operator was developed. In the last diagnosis category, we have developed an algorithm that diagnoses diabetic retinopathy and diabetic macular edema based on the lesions segmented; starting from a single unseen image, our algorithm can generate a diabetic retinopathy and ma cular edema diagnosis in _22 seconds on a 1.6 GHz machine with 4 GB of RAM; additionally, we show the first results of a macular edema detection algorithm based on multiple fundus images, which can potentially identify the swelling of the macula even when no lesions are visible.