No description available.

La rétinopexie transsclérale est une technique de laser non invasive, visant à créer des ancrages de la rétine dans la choroïde, par la formation de multiples lésions de photocoagulation correspondant à des brulures focales reconnues comme cicatrices coagulatives atrophiques. Cette technique est utilisée chez l’humain, surtout chez l’enfant, en prévention d’un décollement de rétine. Malgré la procédure de laser, un re-décollement de la neurorétine est toujours possible. Cette technique est utilisée chez le chien, mais son application pourrait être utilisée sur un éventail d’espèces plus large, si un suivi des lésions de photocoagulation pouvait être effectué dans le temps afin de s’assurer de la conformité des cicatrices choriorétiniennes. La tomographie par cohérence optique (OCT), grâce à son grand pouvoir de résolution, de l’ordre de microns, pourrait être un outil efficace permettant de vérifier la structure des lésions de photocoagulation in vivo. À cet effet, notre étude a évalué la corrélation entre les coupes sagittales de lésion de photocoagulation, par histologie et OCT, en utilisant le lapin comme modèle animal. Notre étude a illustré la corrélation entre les images de photocoagulation à l’histologie et à l’OCT aux jours (J) 1, 7, 21 et 42 après le traitement laser. La diminution graduelle de la neurorétine, avec un aspect atrophique apparent dès J7, était visible dans les images d’histologie et d’OCT. L’hyperpigmentation histologique avait une claire correspondance avec l’hyper-brillance de la coupe OCT à J42. L’OCT semble être un outil précis et efficace pour le suivi d’une cicatrice choriorétinienne, effectuée au laser diode 810 nm. / Trans-scleral retinopexy is a non-invasive laser technique, aiming at anchoring the retina to the choroid, by producing multiple photocoagulation lesions corresponding to focal burns, named atrophic coagulating scars. This technique is used in humans, especially in children, to prevent retinal detachment. Despite the laser procedure, a re-detachment of the neuroretina is still possible. This technique is used mostly in dogs, but its application could be extended to other species, if a follow-up of the lesions could be carried out over time to ensure the conformity of the chorioretinal scars. Optical coherence tomography (OCT), thanks to its very high-resolution power, in the order of microns, could be an effective tool to evaluate photocoagulation lesions in vivo. For this purpose, a correlation between sagittal sections of photocoagulation lesions by histology and OCT was performed, using the rabbit as an animal model. Our study illustrated a comparison between histology and OCT photocoagulation images at days (D) 1, 7, 21 and 42 after laser treatment. The gradual decrease in neuroretinal thickness, with an atrophic appearance, was present as early as D7, and visible in both histology and OCT. The histological hyperpigmentation clearly corresponded to the hyper-brilliance of the OCT images at D42. The OCT appears to be a precise and effective tool for the follow-up over time of a chorioretinal scar, performed with an 810 nm diode laser.

Optical Coherence Tomography (OCT) has been around for more than 30 years and is still being continuously improved. The department of ophthalmology is a part of Sahlgrenska Hospital that heavily uses OCT for helping people with the treatment of eye diseases. They are currently facing a problem where the time to go from an OCT scan to treatment is being increased due to having an overload of patient visits every day. Since it requires a trained expert to analyze each OCT scan, the increase of patients is too overwhelming for the few experts that the department has. It is believed that the next phase of this medical field will be through the adoption of machine learning technology. This thesis has been issued by Sahlgrenska University Hospital (SUH), and they want to address the problem that ophthalmology has by introducing the use of machine learning into their workflow. This thesis aims to determine the best suited CNN through training and testing of pre-trained models and to build a tool that a model can be integrated into for use in ophthalmology. Transfer learning was used to compare three different types of pre-trained models offered by Keras, namely VGG16, InceptionResNet50V2 and ResNet50V2. They were all trained on an open dataset containing 84495 OCT images categorized into four different classes. These include the three diseases Choroidal Neovascularization (CNV), Diabetic Macular Edema (DME), drusen and normal eyes. To further improve the accuracy of the models, oversampling, undersampling, and data augmentation were applied to the training set and then tested in different variations. A web application was built using Tensorflow.js and Node.js that the best-performed model later was integrated into. The VGG16 model performed the best with only oversampling applied out of the three. It yielded an average of 95% precision, 95% recall and got a 95% F1-score. The second was the Inception model with only oversampling applied that got an average of 93% precision, 93% recall and a 93% F1-score. Last came the ResNet model with an average of 93% precision, 92% recall and a 92% F1-score. The results suggest that oversampling is the overall best technique for this given dataset. The chosen data augmentation techniques only lead to models performing marginally worse in all cases. It also suggests that pre-trained models with more parameters, such as the VGG16 model, have more feature mappings and, therefore, achieve higher accuracy. On this basis, parameters and better mappings of features should be taken into account when using pre-trained models.

No description available.

The development of a numeric simulation for predicting the performance of an Ocean Current Energy Conversion System is presented in this thesis along with a control system development using a PID controller for the achievement of specified rotational velocity set-points. In the beginning, this numeric model is implemented in MATLAB/Simulink® and it is used to predict the performance of a three phase squirrel single-cage type induction motor/generator in two different cases. The first case is a small 3 meter rotor diameter, 20 kW ocean current turbine with fixed pitch blades, and the second case a 20 meter, 720 kW ocean current turbine with variable pitch blades. Furthermore, the second case is also used for the development of a Voltage Source Variable Frequency Drive for the induction motor/generator. Comparison among the Variable Frequency Drive and a simplified model is applied. Finally, the simulation is also used to estimate the average electric power generation from the 720 kW Ocean Current Energy Conversion System which consists of an induction generator and an ocean current turbine connected with a shaft which modeled as a mechanical vibration system.

Ce manuscrit de thèse présente l’étude des techniques de super-résolution latérale en nanoscopie optique, qui est une des nouvelles techniques d'imagerie haute résolution, aujourd'hui largement utilisée en biophysique et en imagerie médicale, pour imager et caractériser des nanostructures, tout en conservant les avantages de l'imagerie optique en champ lointain comme un vaste champ, la visualisation et l’analyse en temps réel…Un des défis futurs de la microscopie 3D super-résolue est d’éviter l’utilisation des marqueurs fluorescents. La microscopie interférométrique fait partie des techniques d’imagerie 3D sans marquage permettant la détection de nanostructures. Pour améliorer le pouvoir de détection de ce système optique, un premier protocole de traitement d’images a été développé et implémenté, permettant ainsi de révéler des structures initialement non mesurables. Puis, pour améliorer la résolution latérale du système, une nouvelle technique combinant l’interférométrie et le principe du nano-jet photonique a été développée permettant l’observation d’objets de taille inférieure à la limite de diffraction de l’instrument optique. / This manuscript presents the study of the lateral super-resolution techniques in optical nanoscopy, which is a new high-resolution imaging method now widely used in biophysics and medical imaging, to observe and measure nanostructures, with the advantages of far field optical imaging, such as a large field of view, visualization and analysis in real time…One of the future challenges of 3D super resolution microscopy is to avoid the use of fluorescent markers. Interferometric microscopy is a 3D label-free imaging technique enabling the detection of nanostructures. To improve the detection capability of this optical system, a first version of a protocol composed of image processing methods was developed and implemented, revealing structures initially unmeasurable. Then, to improve the lateral resolution of the system, a new technique combining interferometry and the principle of the photonic nano-jet has been developed, thus allowing the observation of objects of a size smaller than the diffraction limit of the optical instrument.

The phosphatidylinositol 3' kinase (PI3K) pathway is involved in many cellular processes including cell proliferation, survival, and glucose transport, and is implicated in various disease states such as cancer and diabetes. Though there have been numerous studies dissecting the role of PI3K signaling in different cell types and disease models, the mechanism by which PI3K signaling regulates embryonic stem (ES) cell fate remains unclear. It is believed that in addition to proliferation and tumorigenicity, PI3K activity might also be important for self-renewal of ES cells. Paling et al. (2004) reported that the inhibition of PI3K led to a reduction in the ability of leukemia inhibitory factor (LIF) to maintain self-renewal causing cells to differentiate. Studies in our lab have revealed that ES cells completely lacking GSK-3 remain undifferentiated compared to wildtype ES cells. GSK-3 is negatively regulated by PI3K suggesting that PI3K may play a vital role in maintaining pluripotency in ES cells through GSK-3. By using a modified Flp recombinase system, we expressed activated alleles of PDK-1 and PKB to create stable, isogenic ES cell lines to further study the role of the PI3K signaling pathway in stem cell fate determination. In vitro characterization of the transgenic cell lines revealed a strong tendency towards maintenance of pluripotency, and this phenotype was found to be independent of canonical Wnt signal transduction. To assess growth and differentiation capacity in vivo, the ES cell lines were grown as subcutaneous teratomas. The constitutively active PDK-1 and PKB ES cell lines were able to form all three germ layers when grown in this manner – in contrast to ES cells engineered to lack GSK-3. The resulting PI3K pathway activated cells exhibited a higher growth rate which resulted in large teratomas. In summary, PI3K signaling is sufficient to maintain self-renewal and survival of stem cells. Since this pathway is frequently mutationally activated in cancers, its effect on suppressing differentiation may contribute to its oncogenicity.

The phosphatidylinositol 3' kinase (PI3K) pathway is involved in many cellular processes including cell proliferation, survival, and glucose transport, and is implicated in various disease states such as cancer and diabetes. Though there have been numerous studies dissecting the role of PI3K signaling in different cell types and disease models, the mechanism by which PI3K signaling regulates embryonic stem (ES) cell fate remains unclear. It is believed that in addition to proliferation and tumorigenicity, PI3K activity might also be important for self-renewal of ES cells. Paling et al. (2004) reported that the inhibition of PI3K led to a reduction in the ability of leukemia inhibitory factor (LIF) to maintain self-renewal causing cells to differentiate. Studies in our lab have revealed that ES cells completely lacking GSK-3 remain undifferentiated compared to wildtype ES cells. GSK-3 is negatively regulated by PI3K suggesting that PI3K may play a vital role in maintaining pluripotency in ES cells through GSK-3. By using a modified Flp recombinase system, we expressed activated alleles of PDK-1 and PKB to create stable, isogenic ES cell lines to further study the role of the PI3K signaling pathway in stem cell fate determination. In vitro characterization of the transgenic cell lines revealed a strong tendency towards maintenance of pluripotency, and this phenotype was found to be independent of canonical Wnt signal transduction. To assess growth and differentiation capacity in vivo, the ES cell lines were grown as subcutaneous teratomas. The constitutively active PDK-1 and PKB ES cell lines were able to form all three germ layers when grown in this manner – in contrast to ES cells engineered to lack GSK-3. The resulting PI3K pathway activated cells exhibited a higher growth rate which resulted in large teratomas. In summary, PI3K signaling is sufficient to maintain self-renewal and survival of stem cells. Since this pathway is frequently mutationally activated in cancers, its effect on suppressing differentiation may contribute to its oncogenicity.

Aufgrund einer möglichen Entnahmemorbidität sind Knorpelschäden am Knie von mehr als 3 cm ² Größe bei der autologen osteochondralen Transplantation (OCT) als kritisch zu betrachten. In dieser Studie wurde untersucht, ob die Entnahmemorbidität beo großen Knorpelschädendurch durch den Einsatz von OBI TruFit Plugs reduziert werden kann. Wir führten die autologe osteochondrale Transplantation bei insgesamt 37 Patienten durch und die Knorpel-Knochen-Zylinder wurden aus dem dorsalen medialen femoralen Kondylus entfernt. Die Defekte an der Entnahmestelle wurde bei 21 Patienten (mit einer durchschnittlichen Defektgröße von 5,5 cm²) mit künstlichen TruFit Plugs gefüllt, bei 16 Patienten (mit einer durchschnittlichen Defektgröße von 4,6 cm2) wurden die Defekte der Entnahmestellen unbehandelt gelassen. Im Durchschnitt wurden die Patienten in der Studiengruppe (mit TruFit Plugs behandelt) nach 12,8 (± 1,8) Monaten postoperativ und nach 25,2 (± 1,8) Monate erneut nachuntersucht; in der Kontrollgruppe (unbehandelt gelassene Entnahmestellen) wurden dieNachuntersuchungen nach 13,8 (± 4,3) Monate durchgeführt sowie nach 58,9 (± 4,0) Monaten. In der Studiengruppe verbesserten sich die Ergebnisse von Tegner-Score, WOMAC, VAS und Knee-Society-Score von präoperativ 3,2 (± 0,8), 60,9 (± 41,6), 133,6 (± 27,1) und 4,8 (± 2,3) auf 3,9 (± 0,6), 35,5 ( ± 27,1), 177,8 (± 16,6) und 3,3 (± 2,9) Punkten zum Zeitpunkt des zweiten Follow-up; die Kontrollgruppe zeigte präoperativ Score-Ergebnisse von 2,8 (± 0,9), 73,3 (± 50,2), 123,8 (± 41,5 ) und 5,3 (± 2,7) Punkten und verbesserte diese auf 3,6 (± 0,8), 41,4 (± 28,8), 179,3 (± 17,5) und 3,1 (± 2,0) Punkte zum Zeitpunkt des zweiten Follow-up. Je kleiner der anfängliche Knorpeldefekt in der Studiengruppe war, desto besser wurden die WOMAC Score-Werte (p < 0,05). Die MRI-Auswertung führte zu einer Verbesserung der Gesamtpunktzahl im modifizierten Henderson in der Studiengruppe an den Entnahmestellen von 19,2 (± 3,3) auf 13,7 (± 2,1) Punkte und an der Empfängerstelle von 12,2 (± 2,4) auf 12 (± 1,7) Punkte (p <0,001), die Score-Werte für die die Kontrollgruppe zeigte an den Entnahmestellen 18,3 (± 3,4) und 15,4 (± 4,4) Punkte sowie für die Empfängerstellen 11,1 (± 1,8) und 13,7 (± 2,6) Punkte (p = 0,0015). OCT ist eine wirksame Therapie auch bei großen Knorpeldefekten> 3 cm ². Die Rückenflosse medialen Femurkondylus ist ein geeigneter Spender Website, zeigt eine niedrige Entnahmemorbidität und eine hohe Regenerationsfähigkeit. Durch das Ausfüllen der Mängel mit TruFit Implantate keine klinischen Verbesserungen gefunden als Entnahmemorbidität bereits niedrig ist sowieso. Allerdings nahm die Regeneration von Defekten mit TruFit Implantate gefüllt mehr als 2 Jahren.

Le glaucome est la première cause de cécité irréversible dans le monde. Bien que sa pathogenèse demeure encore nébuleuse, les propriétés biomécaniques de l’oeil sembleraient jouer un rôle important dans le développement et la progression de cette maladie. Il est stipulé que la rigidité oculaire (RO) est altérée au travers les divers stades de la maladie et qu’elle serait le facteur le plus influent sur la réponse du nerf optique aux variations de la pression intraoculaire (PIO) au sein du glaucome. Pour permettre l’investigation du rôle de la RO dans le glaucome primaire à angle ouvert (GPAO), la capacité de quantifier la RO in vivo par l’entremise d’une méthode fiable et non-invasive est essentielle. Une telle méthode n’est disponible que depuis 2015. Basée sur l'équation de Friedenwald, cette approche combine l'imagerie par tomographie par cohérence optique (TCO) et la segmentation choroïdienne automatisée afin de mesurer le changement de volume choroïdien pulsatile (ΔV), ainsi que la tonométrie dynamique de contour Pascal pour mesurer le changement de pression pulsatile correspondant. L’objectif de cette thèse est d’évaluer la validité de cette méthode, et d’en faire usage afin d’investiguer le rôle de la RO dans les maladies oculaires, particulièrement le GPAO. Plus spécifiquement, cette thèse vise à : 1) améliorer la méthode proposée et évaluer sa validité ainsi que sa répétabilité, 2) investiguer l’association entre la RO et le dommage neuro-rétinien chez les patients glaucomateux, et ceux atteints d’un syndrome de vasospasticité, 3) évaluer l’association entre la RO et les paramètres biomécaniques de la cornée, 4) évaluer l’association entre la RO et les pics de PIO survenant suite aux thérapies par injections intravitréennes (IIV), afin de les prédire et de les prévenir chez les patients à haut risque, et 5) confirmer que la RO est réduite dans les yeux myopes. D’abord, nous avons amélioré le modèle mathématique de l’oeil utilisé pour dériver ΔV en le rendant plus précis anatomiquement et en tenant compte de la choroïde périphérique. Nous avons démontré la validité et la bonne répétabilité de cette méthodologie. Puis, nous avons effectué la mesure des coefficients de RO sur un large éventail de sujets sains et glaucomateux en utilisant notre méthode non-invasive, et avons démontré, pour la première fois, qu'une RO basse est corrélée aux dommages glaucomateux. Les corrélations observées étaient comparables à celles obtenues avec des facteurs de risque reconnus tels que la PIO maximale. Une forte corrélation entre la RO et les dommages neuro-rétiniens a été observée chez les patients vasospastiques, mais pas chez ceux atteints d'une maladie vasculaire ischémique. Cela pourrait potentiellement indiquer une plus grande susceptibilité au glaucome due à la biomécanique oculaire chez les patients vasospastiques. Bien que les paramètres biomécaniques cornéens aient été largement adoptés dans la pratique clinique en tant que substitut pour la RO, propriété biomécanique globale de l'oeil, nous avons démontré une association limitée entre la RO et ces paramètres, offrant une nouvelle perspective sur la relation entre les propriétés biomécaniques cornéennes et globales de l’oeil. Seule une faible corrélation entre le facteur de résistance cornéenne et la RO demeure après ajustement pour les facteurs de confusion dans le groupe des patients glaucomateux. Ensuite, nous avons présenté un modèle pour prédire l'amplitude des pics de PIO après IIV à partir de la mesure non-invasive de la RO. Ceci est particulièrement utile pour les patients à haut risque atteints de maladies rétiniennes exsudatives et de glaucome qui nécessiteraient des IIV thérapeutiques, et pourrait permettre aux cliniciens d'ajuster ou de personnaliser le traitement pour éviter toute perte de vision additionnelle. Enfin, nous avons étudié les différences de RO entre les yeux myopes et les non-myopes en utilisant cette technique, et avons démontré une RO inférieure dans la myopie axiale, facteur de risque du GPAO. Dans l'ensemble, ces résultats contribuent à l’avancement des connaissances sur la physiopathologie du GPAO. Le développement de notre méthode permettra non seulement de mieux explorer le rôle de la RO dans les maladies oculaires, mais contribuera également à élucider les mécanismes et développer de nouveaux traitements ciblant la RO pour contrer la déficience visuelle liée à ces maladies. / Glaucoma is the leading cause of irreversible blindness worldwide. While its pathogenesis is yet to be fully understood, the biomechanical properties of the eye are thought to be involved in the development and progression of this disease. Ocular rigidity (OR) is thought to be altered through disease processes and has been suggested to be the most influential factor on the optic nerve head’s response to variations in intraocular pressure (IOP) in glaucoma. To further investigate the role of OR in open-angle glaucoma (OAG) and other ocular diseases such as myopia, the ability to quantify OR in living human eyes using a reliable and non-invasive method is essential. Such a method has only become available in 2015. Based on the Friedenwald equation, the method uses time-lapse optical coherence tomography (OCT) imaging and automated choroidal segmentation to measure the pulsatile choroidal volume change (ΔV), and Pascal dynamic contour tonometry to measure the corresponding pulsatile pressure change. The purpose of this thesis work was to assess the validity of the methodology, then use it to investigate the role of OR in ocular diseases, particularly in OAG. More specifically, the objectives were: 1) To improve the extrapolation of ΔV and evaluate the method’s validity and repeatability, 2) To investigate the association between OR and neuro-retinal damage in glaucomatous patients, as well as those with concomitant vasospasticity, 3) To evaluate the association between OR and corneal biomechanical parameters, 4) To assess the association between OR and IOP spikes following therapeutic intravitreal injections (IVIs), to predict and prevent them in high-risk patients, and 5) To confirm that OR is lower in myopia. First, we improved the mathematical model of the eye used to derive ΔV by rendering it more anatomically accurate and accounting for the peripheral choroid. We also confirmed the validity and good repeatability of the method. We carried out the measurement of OR coefficients on a wide range of healthy and glaucomatous subjects using this non-invasive method, and were able to show, for the first time, that lower OR is correlated with more glaucomatous damage. The correlations observed were comparable to those obtained with recognized risk factors such as maximum IOP. A strong correlation between OR and neuro-retinal damage was found in patients with concurrent vasospastic syndrome, but not in those with ischemic vascular disease. This could perhaps indicate a greater susceptibility to glaucoma due to ocular biomechanics in vasospastic patients. While corneal biomechanical parameters have been widely adopted in clinical practice as surrogate measurements for the eye’s overall biomechanical properties represented by OR, we have shown a limited association between these parameters, bringing new insight unto the relationship between corneal and global biomechanical properties. Only a weak correlation between the corneal resistance factor and OR remained in glaucomatous eyes after adjusting for confounding factors. In addition, we presented a model to predict the magnitude of IOP spikes following IVIs from the non-invasive measurement of OR. This is particularly useful for high-risk patients with exudative retinal diseases and glaucoma that require therapeutic IVIs, and could provide the clinician an opportunity to adjust or customize treatment to prevent further vision loss. Finally, we investigated OR differences between non-myopic and myopic eyes using this technique, and demonstrated lower OR in axial myopia, a risk factor for OAG. Overall, these findings provide new insights unto the pathophysiology of glaucomatous optic neuropathy. The development of our method will permit further investigation of the role of OR in ocular diseases, contributing to elucidate mechanisms and provide novel management options to counter vision impairment caused by these diseases.