133 research outputs found

    NOVEL METHODS OF MERIDIONAL AND CIRCUMFERENTIAL ANTERIOR CHAMBER ANGLE IMAGING

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    Ph.DDOCTOR OF PHILOSOPH

    Machine Learning Approaches for Automated Glaucoma Detection using Clinical Data and Optical Coherence Tomography Images

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    Glaucoma is a multi-factorial, progressive blinding optic-neuropathy. A variety of factors, including genetics, vasculature, anatomy, and immune factors, are involved. Worldwide more than 80 million people are affected by glaucoma, and around 300,000 in Australia, where 50% remain undiagnosed. Untreated glaucoma can lead to blindness. Early detection by Artificial intelligence (AI) is crucial to accelerate the diagnosis process and can prevent further vision loss. Many proposed AI systems have shown promising performance for automated glaucoma detection using two-dimensional (2D) data. However, only a few studies had optimistic outcomes for glaucoma detection and staging. Moreover, the automated AI system still faces challenges in diagnosing at the clinicians’ level due to the lack of interpretability of the ML algorithms and integration of multiple clinical data. AI technology would be welcomed by doctors and patients if the "black box" notion is overcome by developing an explainable, transparent AI system with similar pathological markers used by clinicians as the sign of early detection and progression of glaucomatous damage. Therefore, the thesis aimed to develop a comprehensive AI model to detect and stage glaucoma by incorporating a variety of clinical data and utilising advanced data analysis and machine learning (ML) techniques. The research first focuses on optimising glaucoma diagnostic features by combining structural, functional, demographic, risk factor, and optical coherence tomography (OCT) features. The significant features were evaluated using statistical analysis and trained in ML algorithms to observe the detection performance. Three crucial structural ONH OCT features: cross-sectional 2D radial B-scan, 3D vascular angiography and temporal-superior-nasal-inferior-temporal (TSNIT) B-scan, were analysed and trained in explainable deep learning (DL) models for automated glaucoma prediction. The explanation behind the decision making of DL models were successfully demonstrated using the feature visualisation. The structural features or distinguished affected regions of TSNIT OCT scans were precisely localised for glaucoma patients. This is consistent with the concept of explainable DL, which refers to the idea of making the decision-making processes of DL models transparent and interpretable to humans. However, artifacts and speckle noise often result in misinterpretation of the TSNIT OCT scans. This research also developed an automated DL model to remove the artifacts and noise from the OCT scans, facilitating error-free retinal layers segmentation, accurate tissue thickness estimation and image interpretation. Moreover, to monitor and grade glaucoma severity, the visual field (VF) test is commonly followed by clinicians for treatment and management. Therefore, this research uses the functional features extracted from VF images to train ML algorithms for staging glaucoma from early to advanced/severe stages. Finally, the selected significant features were used to design and develop a comprehensive AI model to detect and grade glaucoma stages based on the data quantity and availability. In the first stage, a DL model was trained with TSNIT OCT scans, and its output was combined with significant structural and functional features and trained in ML models. The best-performed ML model achieved an area under the curve (AUC): 0.98, an accuracy of 97.2%, a sensitivity of 97.9%, and a specificity of 96.4% for detecting glaucoma. The model achieved an overall accuracy of 90.7% and an F1 score of 84.0% for classifying normal, early, moderate, and advanced-stage glaucoma. In conclusion, this thesis developed and proposed a comprehensive, evidence-based AI model that will solve the screening problem for large populations and relieve experts from manually analysing a slew of patient data and associated misinterpretation problems. Moreover, this thesis demonstrated three structural OCT features that could be added as excellent diagnostic markers for precise glaucoma diagnosis

    Multi-modal imaging in Ophthalmology: image processing methods for improving intra-ocular tumor treatment via MRI and Fundus image photography

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    The most common ocular tumors in the eye are retinoblastoma and uveal melanoma, affecting children and adults respectively, and spreading throughout the body if left untreated. To date, detection and treatment of such tumors rely mainly on two imaging modalities: Fundus Image Photography (Fundus) and Ultrasound (US), however, other image modalities such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are key to confirm a possible tumor spread outside the eye cavity. Current procedures to select the best treatment and follow-up are based on manual multimodal measures taken by clinicians. These tasks often require the manual annotation and delineation of eye structures and tumors, a rather tedious and time consuming endeavour, to be performed in multiple medical sequences simultaneously. ################################ This work presents a new set of image processing methods for improving multimodal evaluation of intra-ocular tumors in 3D MRI and 2D Fundus. We first introduce a novel technique for the automatic delineation of ocular structures and tumors in the 3D MRI. To this end, we present an Active Shape Model (ASM) built out of a dataset of healthy patients to demonstrate that the segmentation of ocular structures (e.g. the lens, the vitreous humor, the cornea and the sclera) can be performed in an accurate and robust manner. To validate these findings, we introduce a set of experiments to test the model performance on eyes with presence of endophytic retinoblastoma, and discover that the segmentation of healthy eye structures is possible, regardless of the presence of the tumor inside the eyes. Moreover, we propose a specific set of Eye Patient-specific eye features that can be extracted -- Le rétinoblastome et le mélanome uvéal sont les types de cancer oculaire les plus communs, touchant les enfants et adultes respectivement, et peuvent se répandre à travers l’organisme s’ils ne sont pas traités. Actuellement, le traitement pour la détection du rétinoblastome se base essentiellement à partir de deux modalites d’imagerie fond d’œil (Fundus) et l’ultrason (US). Cependant, d’autres modalités d’imagerie comme l’Imagerie par Résonance magnétique (IRM) et la Tomodensitométrie (TDM) sont clé pour confirmer la possible expansion du cancer en dehors de la cavité oculaire. Les techniques utilisées pour déterminer la tumeur oculaire, ainsi que le choix du traitement, se basent sur des mesures multimodales réalisées de manière manuelle par des médecins. Cette méthodologie manuelle est appliquée quotidiennement et continuellement pendant toute la durée de la maladie. Ce processus nécessite souvent la délinéation manuelle des structures ocularies et de la tumeur, un mécanisme laborieux et long, effectuée dans des multiples séquences médicales simultanées (par exemple : T1-weighted et T2-weighted IRM ...) qui augmentent la difficulté pour évaluer la maladie. Le présent travail présente une nouvelle série de techniques permettant d’améliorer l´évaluation multimodale de tumeurs oculaires en IRM et Fundus. Dans un premier temps, nous intro- duisons une méthode qui assure la délinéation automatique de la structure oculaire et de la tumeur dans un IRM 3D. Pour cela, nous présentons un Active Shape Model (ASM) construite à partir d’un ensemble de données de patients en bonne santé pour prouver que la segmenta- tion automatique de la structure oculaire (par exemple : le cristallin, l´humeur aqueuse, la cornée et la sclère) peut être réalisée de manière précise et robuste. Afin de valider ces résultats, nous introduisons un ensemble d’essais pour tester la performance du modèle par rapport à des yeux de patients affectés pathologiquement par un rétinoblastome, et démontrons que la segmentation de la structure oculaire d’un œil sain est possible, indépendamment de la présence d’une tumeur à l’intérieur des yeux. De plus, nous proposons une caractérisation spécifique du patient-specific eye features qui peuvent être utile pour la segmentation de l’œil dans l’IRM 3D, fournissant des formes riches et une information importante concernant le tissu pathologique noyé dans la structure oculaire de l’œil sain. Cette information est ultérieurement utilisée pour entrainer un ensemble de classificateurs (Convolutional Neural Network (CNN), Random Forest, . . . ) qui réalise la segmentation automatique de tumeurs oculaires à l’intérieur de l’œil. En outre, nous explorons une nouvelle méthode pour évaluer des multitudes de séquences d’images de manière simultanée, fournissant aux médecins un outil pour observer l’extension de la tumeur dans le fond d’œil et l’IRM. Pour cela, nous combinons la segmentation auto- matique de l’œil de l’IRM selon la description ci-dessus et nous proposons une delineation manuelle de tumeurs oculaires dans le fond d’œil. Ensuite, nous recalons ces deux modalités d’imagerie avec une nouvelle base de points de repère et nous réalisons la fusion des deux modalités. Nous utilisons cette nouvelle méthode pour (i) améliorer la qualité de la délinéation dans l’IRM et pour (ii) utiliser la projection arrière de la tumeur pour transporter de riches me- sures volumétriques de l’IRM vers le fond d’œil, en créant une nouvelle forme 3D représentant le fond d’œil 2D dans une méthode que nous appelons Topographic Fundus Mapping. Pour tous les tests et contributions, nous validons les résultats avec une base de données d’IRM et une base de données d’images pathologiques du fond d’œil de rétinoblastome

    Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography

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    Tesis por compendio[ES] Esta tesis presenta soluciones de vanguardia basadas en algoritmos de computer vision (CV) y machine learning (ML) para ayudar a los expertos en el diagnóstico clínico. Se centra en dos áreas relevantes en el campo de la imagen médica: la patología digital y la oftalmología. Este trabajo propone diferentes paradigmas de machine learning y deep learning para abordar diversos escenarios de supervisión en el estudio del cáncer de próstata, el cáncer de vejiga y el glaucoma. En particular, se consideran métodos supervisados convencionales para segmentar y clasificar estructuras específicas de la próstata en imágenes histológicas digitalizadas. Para el reconocimiento de patrones específicos de la vejiga, se llevan a cabo enfoques totalmente no supervisados basados en técnicas de deep-clustering. Con respecto a la detección del glaucoma, se aplican algoritmos de memoria a corto plazo (LSTMs) que permiten llevar a cabo un aprendizaje recurrente a partir de volúmenes de tomografía por coherencia óptica en el dominio espectral (SD-OCT). Finalmente, se propone el uso de redes neuronales prototípicas (PNN) en un marco de few-shot learning para determinar el nivel de gravedad del glaucoma a partir de imágenes OCT circumpapilares. Los métodos de inteligencia artificial (IA) que se detallan en esta tesis proporcionan una valiosa herramienta de ayuda al diagnóstico por imagen, ya sea para el diagnóstico histológico del cáncer de próstata y vejiga o para la evaluación del glaucoma a partir de datos de OCT.[CA] Aquesta tesi presenta solucions d'avantguarda basades en algorismes de *computer *vision (CV) i *machine *learning (ML) per a ajudar als experts en el diagnòstic clínic. Se centra en dues àrees rellevants en el camp de la imatge mèdica: la patologia digital i l'oftalmologia. Aquest treball proposa diferents paradigmes de *machine *learning i *deep *learning per a abordar diversos escenaris de supervisió en l'estudi del càncer de pròstata, el càncer de bufeta i el glaucoma. En particular, es consideren mètodes supervisats convencionals per a segmentar i classificar estructures específiques de la pròstata en imatges histològiques digitalitzades. Per al reconeixement de patrons específics de la bufeta, es duen a terme enfocaments totalment no supervisats basats en tècniques de *deep-*clustering. Respecte a la detecció del glaucoma, s'apliquen algorismes de memòria a curt termini (*LSTMs) que permeten dur a terme un aprenentatge recurrent a partir de volums de tomografia per coherència òptica en el domini espectral (SD-*OCT). Finalment, es proposa l'ús de xarxes neuronals *prototípicas (*PNN) en un marc de *few-*shot *learning per a determinar el nivell de gravetat del glaucoma a partir d'imatges *OCT *circumpapilares. Els mètodes d'intel·ligència artificial (*IA) que es detallen en aquesta tesi proporcionen una valuosa eina d'ajuda al diagnòstic per imatge, ja siga per al diagnòstic histològic del càncer de pròstata i bufeta o per a l'avaluació del glaucoma a partir de dades d'OCT.[EN] This thesis presents cutting-edge solutions based on computer vision (CV) and machine learning (ML) algorithms to assist experts in clinical diagnosis. It focuses on two relevant areas at the forefront of medical imaging: digital pathology and ophthalmology. This work proposes different machine learning and deep learning paradigms to address various supervisory scenarios in the study of prostate cancer, bladder cancer and glaucoma. In particular, conventional supervised methods are considered for segmenting and classifying prostate-specific structures in digitised histological images. For bladder-specific pattern recognition, fully unsupervised approaches based on deep-clustering techniques are carried out. Regarding glaucoma detection, long-short term memory algorithms (LSTMs) are applied to perform recurrent learning from spectral-domain optical coherence tomography (SD-OCT) volumes. Finally, the use of prototypical neural networks (PNNs) in a few-shot learning framework is proposed to determine the severity level of glaucoma from circumpapillary OCT images. The artificial intelligence (AI) methods detailed in this thesis provide a valuable tool to aid diagnostic imaging, whether for the histological diagnosis of prostate and bladder cancer or glaucoma assessment from OCT data.García Pardo, JG. (2022). Machine learning strategies for diagnostic imaging support on histopathology and optical coherence tomography [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182400Compendi

    Human retinal oximetry using hyperspectral imaging

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    The aim of the work reported in this thesis was to investigate the possibility of measuring human retinal oxygen saturation using hyperspectral imaging. A direct non-invasive quantitative mapping of retinal oxygen saturation is enabled by hyperspectral imaging whereby the absorption spectra of oxygenated and deoxygenated haemoglobin are recorded and analysed. Implementation of spectral retinal imaging thus requires ophthalmic instrumentation capable of efficiently recording the requisite spectral data cube. For this purpose, a spectral retinal imager was developed for the first time by integrating a liquid crystal tuneable filter into the illumination system of a conventional fundus camera to enable the recording of narrow-band spectral images in time sequence from 400nm to 700nm. Postprocessing algorithms were developed to enable accurate exploitation of spectral retinal images and overcome the confounding problems associated with this technique due to the erratic eye motion and illumination variation. Several algorithms were developed to provide semi-quantitative and quantitative oxygen saturation measurements. Accurate quantitative measurements necessitated an optical model of light propagation into the retina that takes into account the absorption and scattering of light by red blood cells. To validate the oxygen saturation measurements and algorithms, a model eye was constructed and measurements were compared with gold-standard measurements obtained by a Co-Oximeter. The accuracy of the oxygen saturation measurements was (3.31%± 2.19) for oxygenated blood samples. Clinical trials from healthy and diseased subjects were analysed and oxygen saturation measurements were compared to establish a merit of certain retinal diseases. Oxygen saturation measurements were in agreement with clinician expectations in both veins (48%±9) and arteries (96%±5). We also present in this thesis the development of novel clinical instrument based on IRIS to perform retinal oximetry.Al-baath University, Syri

    Structural and biochemical investigations of the cornea and the trabecular meshwork

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    The experiments which comprise this thesis focused on structure-function relationships in two distinct collagen-rich connective tissues of the eye, the cornea and the trabecular meshwork. The cornea is the transparent tissue that covers the front of the eye and has the ability to transmit and refract light. Corneal transparency is the result of the unique organisation of collagen fibrils in the corneal stroma matrix, of which sulphated proteoglycans are key regulators, owing to the presumed importance of the sulfation pattern of corneal proteoglycans. The trabecular meshwork is the sponge-like tissue located around the cornea through which the bulk of the aqueous humor flows towards the juxtacanalicular tissue and the inner wall of Schlemm’s canal to exit the eye and control intraocular pressure. First part of the current research examined the chemical composition and sulphur speciation during corneal embryogenesis in order to elucidate important changes in the biochemical signature of the corneal matrix associated with the acquisition of transparency. It also investigated the content and distribution of distinct sulphur species through the depth of the mature corneal stroma and assessed biochemical-functional relationships that ultimate render tissue transparency. The research also studied the three-dimensional ultrastructure of the human trabecular meshwork, particularly the ultrastructure of the juxtacanalicular tissue that lies adjacent to the inner wall of Schlemm’s canal and the three-dimensional assembly of collagen type VI in the trabecular meshwork itself. X-ray fluorescence microscopy revealed key differences in the chemical composition of the cornea of the developing chick. In particular, the chemical signature of phosphorus, chlorine, sulphur, potassium and calcium were observably different during the developmental period from day 12 to day 16. S k-edge x-ray near edge structure spectroscopy showed that the main sulphur species present in the embryonic cornea were thiols, organic monosulfides, ester sulphate and inorganic sulphate. The chemical signature of these sulphur species was also noticeably different during embryonic corneal development. The changes in the chemical signature of phosphorus with development are believed to underline changes in the presumptive keratocyte population within the embryonic corneal stroma. Chlorine, potassium and calcium are important elements involved in the regulation and balance of the net negative or positive charge of the embryonic cornea and may influence the interactions of corneal matrix molecules. The changes in the sulphur speciation character amongst different developmental corneas are associated with changes in the sulphation status of corneal proteoglycans which play a fundamental role in governing tissue structure and function, and thus transparency. With regards to the sulphur speciation across the depth of the mature corneal stroma, it was found that there is an inconsistency in the sulphur content and distribution throughout the depth of the tissue, from the stromal region closest to the epithelium against the deeper stromal regions near the endothelium. The heterogeneity of the sulphur species in the most anterior part of the mature corneal stroma, at the interface with the Bowman’s layer supports the view that the differentiation and the transition between these two corneal layers is not very abrupt. The rest of the mature corneal stroma depth does not show any differences regarding its content in the sulphur-containing compounds indicating that the distribution and sulfation status of the corneal glycosaminoglycans have very little impact on the overall sulfur speciation. The three-dimensional ultrastructure of the human trabecular meshwork in large volumes and at high resolution identified giant vacuoles in the endothelial cell layer of the inner wall of Schlemm’s canal and these were grouped into four categories based on whether they formed pores, basal and apical, or not. Interestingly, the distribution of these vacuoles was found to be non-uniform. It was discovered that the juxtacanalicular tissue was not homogenous with respect to the proportion of the electron lucent, matrix free spaces throughout the tissue’s depth away from the inner wall of Schlemm’s canal. Three-dimensional reconstructions of collagen type VI in the trabecular meshwork showed that there is no structural regularity in the organisation of type VI collagen assemblies, or their association with sulphated proteoglycans, suggesting a role in aqueous humor outflow. This data allow us to propose a model of aqueous humor outflow and how this is funneled through the juxtacanalicular tissue towards the lumen of Sclemm’s canal

    Glaucoma

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    This book addresses the basic and clinical science of glaucomas, a group of diseases that affect the optic nerve and visual fields and is usually accompanied by increased intraocular pressure. The book incorporates the latest development as well as future perspectives in glaucoma, since it has expedited publication. It is aimed for specialists in glaucoma, researchers, general ophthalmologists and trainees to increase knowledge and encourage further progress in understanding and managing these complicated diseases
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