Thesis (M.S.)--Rochester Institute of Technology, 2005. / Typescript. Includes bibliographical references (leaves 54-56).

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第17826号 / 医博第3824号 / 新制||医||999(附属図書館) / 30641 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 村井 俊哉, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications. </p><p>Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.</p><p>Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.</p> / Dissertation

[Truncated abstract] Purpose: To improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature in in-vitro and in-vivo eye models in which retinal blood flow can be manipulated. Methods: The first experiments utilised an isolated perfused pig eyes perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from zero to 300 μl/min. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate (FITC), for fluorescence microscopy. Using the standard HRF software and a 10×10 pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement regions was determined. For the second study, HRF flow images were acquired at retinal sites in Brown Norway rats over a range of focus levels before and after cessation of retinal blood flow by laser-induced central retinal artery occlusion. Using the 10×10 pixel and 4×4 pixel measurement windows, HRF measured flow was performed in retinal artery, vein, arteriole, capillary and choroidal vessel locations. The relationship between HRF measured flow and focus depth was determined for each location before and after central retinal artery occlusion. At the conclusion of each experiment the effect of reduction of systemic blood pressure (by exsanguination) on HRF flow measurements in choroidal vessels and in locations without visible choroidal vessels was assessed. Finally, HRF flow measurements were acquired after euthanasia, to determine the HRF flow signal which was still present under zero biological flow conditions (the zerooffset). Results: In the isolated perfused pig eye experiments it was found that the HRF flow response varied according to vascular location. At zero perfusate flow, HRF flow was consistently greater than zero at all locations, averaging 171.9 ± 44.7 AU (n=97), representing background noise. Arteries and veins yielded the highest HRF measured flow values, but the relationship between HRF measured flow and perfusate flow was not linear. In arterioles the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that in arteries and veins. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles.

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

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome. / This thesis describes a new clinical and technological approach to the diagnosis of glaucoma. Specifically, we intend to study a new way to detect glaucoma by measuring rim area to disc area asymmetry ratio (RADAAR). For this purpose, we use a database consisting of a population divided into 4 different diagnostic groups (normal, possible glaucoma, probable glaucoma and definitive glaucoma). The RADAAR measurements are calculated in different ways based on the stereometric parameters of the optic nerve head of subjects, produced by confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). We conduct an analysis of data with SPSS or we put forward the RADAAR distribution in different populations, its validity in detecting open angle glaucoma and its usefulness in screening for glaucoma. We therefore enroll 523 subjects in this study with about 82 subjects with definitive glaucoma. The average age is 62 years. There are more females than males and more Caucasians than Africans Caraibeans. We find that the distribution of RADAAR measures is different in each diagnosis group. In terms of performance, the sensitivity of the RADAAR measurement is very low. So, its ability to detect the disease is low. However the RADAAR measure is much more specific so, its ability to identify subjects free of the disease is high. RADAAR measure would also be much more effective in African Caribbean’s than in Caucasians. Similarly, it would be much more sensitive in males than in females. The RADAAR measurement is useful if it is combined with another method of diagnosis like the Moorfields regression analysis (MRA) included in the HRT3 software especially in case of the detection of glaucoma in populations at high risk. Ultimately, we determine that the RADAAR is an interesting tool for the diagnosis of glaucoma particularly in the context of screening for glaucoma.

This work deals with possibilities of registration of retinal images from different mo-dalities, concretely optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO) and fundus camera. In first stage is the interest focused on registration of SLO and fundus images, which will serve to determine area of interest for consecutive registration of OCT data. The final stage is finding correct location of OCT B-scans in fundus image. On the basis of the studied methods of registration was chosen method making use of computation of correlation coefficient for both cases. For finding optimal parameters of registration is used searching through whole space of parameters. In partial stages of the work was created algorithm for alignment of B-scans followed by detection of blood vessels and also simple algorithm for detection of blood vessels from fundus image. For more transparent registration the graphical user interface was created, which allows loading input images and displaying the result in several possible forms.