32 research outputs found
Machine Learning Approaches for Automated Glaucoma Detection using Clinical Data and Optical Coherence Tomography Images
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
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Optical designs and image processing algorithms for optical coherence tomography detection of glaucoma
textOptical Coherence Tomography (OCT) is an optical tomography technique which provides high resolution non-invasive three-dimensional (3D) structural images of the sample based on coherent properties of light. The dissertation focuses on the use of OCT systems for detecting glaucoma, which is the second leading cause of blindness worldwide. First, as a prerequisite of analyzing ophthalmologic OCT images, a retinal sublayer segmentation algorithm is presented and implemented with GPU assisted computation. Then, a polarization-sensitive optical coherence tomography (PS-OCT) system was constructed for the study of glaucoma. Three closely related clinical and animal studies on early-stage glaucoma detection using either OCT or PS-OCT were performed. Statistical analysis of the study results indicates that the scattering property of retinal nerve fiber layer (RNFL) is the earliest indicator for glaucoma. Finally, to investigate the scattering properties of RNFL, a pathlength-multiplexed scattering-angle-diverse optical coherence tomography (PM-SAD-OCT) system was designed and built. PM-SAD-OCT images were collected from human and rodent retina as well as earthworm nerve cord. PM-SAD-OCT system shows promising potentials to detect neurodegenerative diseases including glaucoma.Biomedical Engineerin
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Knowledge Mining In The Clinical Assessment Of Glaucoma
Glaucoma is a leading cause of irreversible blindness and visual impairment. In the clinic, glaucomatous damage can be characterized by structural changes in the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) that can be evaluated by various retinal-imaging techniques such as scanning laser polarimetry and optical coherence tomography (OCT). The structural damage can lead to functional damage in the visual field (VF), normally assessed with standard automated perimetry, which assesses the differential light sensitivity in the field of view. The clinical measurements of retinal structure and visual function play an important role in the detection and management of glaucoma, but the data generated is often complex and highly variable, thus making it hard to clinically interpret. The purpose of this thesis was to investigate knowledge mining procedures for extracting clinically useful information from these measurements. Knowledge mining describes iterative divide-and-conquer type analyses of large-scale questions: solutions to individual smaller problems are used to generate better quality knowledge, which in the case of work reported in this thesis can be translated into clinically useful analysis tools. This thesis describes five knowledge mining procedures specifically developed and applied to structural and functional measurements in glaucoma: (1) probabilistic inference to aid image acquisition of OCT images; (2) a robust and efficient segmentation algorithm to extract features of retina tissue layer structures in large-scale 3-dimensional image volumes acquired by OCT; (3) a predictive structure-function relationship model to bridge the retinal structure and visual function measurements in glaucoma; (4) quantification and visualization of structure-function discordance using the model about structure-function relationship; (5) integration of structural and functional measurements to improve the reproducibility of the measurements. In conclusion the knowledge mining approaches improved the acquisition and/or accuracy of the measurements and provide new clinical analysis tools to detect and manage glaucoma
Machine Learning for Glaucoma Assessment using Fundus Images
[ES] Las imágenes de fondo de ojo son muy utilizadas por los oftalmólogos para la evaluación de la retina y la detección de glaucoma. Esta patologÃa es la segunda causa de ceguera en el mundo, según estudios de la Organización Mundial de la Salud (OMS).
En esta tesis doctoral, se estudian algoritmos de aprendizaje automático (machine learning) para la evaluación automática del glaucoma usando imágenes de fondo de ojo. En primer lugar, se proponen dos métodos para la segmentación automática. El primer método utiliza la transformación Watershed Estocástica para segmentar la copa óptica y posteriormente medir caracterÃsticas clÃnicas como la relación Copa/Disco y la regla ISNT. El segundo método es una arquitectura U-Net que se usa especÃficamente para la segmentación del disco óptico y la copa óptica.
A continuación, se presentan sistemas automáticos de evaluación del glaucoma basados en redes neuronales convolucionales (CNN por sus siglas en inglés). En este enfoque se utilizan diferentes modelos entrenados en ImageNet como clasificadores automáticos de glaucoma, usando fine-tuning. Esta nueva técnica permite detectar el glaucoma sin segmentación previa o extracción de caracterÃsticas. Además, este enfoque presenta una mejora considerable del rendimiento comparado con otros trabajos del estado del arte.
En tercer lugar, dada la dificultad de obtener grandes cantidades de imágenes etiquetadas (glaucoma/no glaucoma), esta tesis también aborda el problema de la sÃntesis de imágenes de la retina. En concreto se analizaron dos arquitecturas diferentes para la sÃntesis de imágenes, las arquitecturas Variational Autoencoder (VAE) y la Generative Adversarial Networks (GAN). Con estas arquitecturas se generaron imágenes sintéticas que se analizaron cualitativa y cuantitativamente, obteniendo un rendimiento similar a otros trabajos en la literatura.
Finalmente, en esta tesis se plantea la utilización de un tipo de GAN (DCGAN) como alternativa a los sistemas automáticos de evaluación del glaucoma presentados anteriormente. Para alcanzar este objetivo se implementó un algoritmo de aprendizaje semi-supervisado.[CA] Les imatges de fons d'ull són molt utilitzades pels oftalmòlegs per a l'avaluació de la retina i la detecció de glaucoma. Aquesta patologia és la segona causa de ceguesa al món, segons estudis de l'Organització Mundial de la Salut (OMS).
En aquesta tesi doctoral, s'estudien algoritmes d'aprenentatge automà tic (machine learning) per a l'avaluació automà tica del glaucoma usant imatges de fons d'ull. En primer lloc, es proposen dos mètodes per a la segmentació automà tica. El primer mètode utilitza la transformació Watershed Estocà stica per segmentar la copa òptica i després mesurar caracterÃstiques clÃniques com la relació Copa / Disc i la regla ISNT. El segon mètode és una arquitectura U-Net que s'usa especÃficament per a la segmentació del disc òptic i la copa òptica.
A continuació, es presenten sistemes automà tics d'avaluació del glaucoma basats en xarxes neuronals convolucionals (CNN per les sigles en anglès). En aquest enfocament s'utilitzen diferents models entrenats en ImageNet com classificadors automà tics de glaucoma, usant fine-tuning. Aquesta nova tècnica permet detectar el glaucoma sense segmentació prèvia o extracció de caracterÃstiques. A més, aquest enfocament presenta una millora considerable del rendiment comparat amb altres treballs de l'estat de l'art.
En tercer lloc, donada la dificultat d'obtenir grans quantitats d'imatges etiquetades (glaucoma / no glaucoma), aquesta tesi també aborda el problema de la sÃntesi d'imatges de la retina. En concret es van analitzar dues arquitectures diferents per a la sÃntesi d'imatges, les arquitectures Variational Autoencoder (VAE) i la Generative adversarial Networks (GAN). Amb aquestes arquitectures es van generar imatges sintètiques que es van analitzar qualitativament i quantitativament, obtenint un rendiment similar a altres treballs a la literatura.
Finalment, en aquesta tesi es planteja la utilització d'un tipus de GAN (DCGAN) com a alternativa als sistemes automà tics d'avaluació del glaucoma presentats anteriorment. Per assolir aquest objectiu es va implementar un algoritme d'aprenentatge semi-supervisat.[EN] Fundus images are widely used by ophthalmologists to assess the retina and detect glaucoma, which is, according to studies from the World Health Organization (WHO), the second cause of blindness worldwide.
In this thesis, machine learning algorithms for automatic glaucoma assessment using fundus images are studied. First, two methods for automatic segmentation are proposed. The first method uses the Stochastic Watershed transformation to segment the optic cup and measures clinical features such as the Cup/Disc ratio and ISNT rule. The second method is a U-Net architecture focused on the optic disc and optic cup segmentation task.
Secondly, automated glaucoma assessment systems using convolutional neural networks (CNNs) are presented. In this approach, different ImageNet-trained models are fine-tuned and used as automatic glaucoma classifiers. These new techniques allow detecting glaucoma without previous segmentation or feature extraction. Moreover, it improves the performance of other state-of-art works.
Thirdly, given the difficulty of getting large amounts of glaucoma-labelled images, this thesis addresses the problem of retinal image synthesis. Two different architectures for image synthesis, the Variational Autoencoder (VAE) and Generative Adversarial Networks (GAN) architectures, were analysed. Using these models, synthetic images that were qualitative and quantitative analysed, reporting state-of-the-art performance, were generated.
Finally, an adversarial model is used to create an alternative automatic glaucoma assessment system. In this part, a semi-supervised learning algorithm was implemented to reach this goal.The research derived from this doctoral thesis has been supported by the Generalitat Valenciana under the scholarship Santiago GrisolÃa [GRISOLIA/2015/027].DÃaz Pinto, AY. (2019). Machine Learning for Glaucoma Assessment using Fundus Images [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124351TESI
Deep learning-based improvement for the outcomes of glaucoma clinical trials
Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management.
To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial
Probabilistic Graphical Models for Medical Image Segmentation
Image segmentation constitutes one of the elementary tasks in computer vision. Various variations exists, one of them being the segmentation of layers that entail a natural ordering constraint. One instance of that problem class are the cell layers in the human retina. In this thesis we study a segmentation approach for this problem class, that applies the machinery of probabilistic graphical models. Linked to probabilistic graphical models is the task of inference, that is, given an input scan of the retina, how to obtain an individual prediction or, if possible, a distribution over potential segmentations of that scan. In general, exact inference is unfeasible which is why we study an approximative approach based on variational inference, that allows to efficiently approximate the full posterior distribution. A distinguishing feature of our approach is the incorporation of a prior shape model, which is not restricted to local information. We evaluate our approach for different data sets, including pathological scans, and demonstrate how global shape information yields
state-of-the-art segmentation results. Moreover, since we approximatively infer the full posterior distribution, we are able to assess the quality of our prediction as well
as rate the scan in terms of its abnormality. Motivated by our problem we also investigate non-parametric density estimation with a log-concavity constraint. This class of density functions is restricted to the convex hull of the empirical data, which naturally leads to shape distributions that comply with the ordering constraint of
retina layers, by not assigning any probability mass to invalid shape configurations. We investigate a prominent approach from the literature, show its extensions from
2-D to N-D and apply it to retina boundary data
Updates on Myopia
This book is open access under a CC BY 4.0 license. This open access book discusses basic clinical concepts of myopia, prevention of progression and surgical treatments for myopia and pathological myopia. It also summarises the latest evidence and best practices for managing myopia, high myopia and its complications. Written by leading experts, the book addresses clinical diagnosis and interpretation of imaging modalities, and various complications of myopia such as glaucoma, choroidal neovascularization, retinal degeneration and cataracts. It is a valuable comprehensive resource for general and sub-specialist ophthalmologists as well as residents and ophthalmologists in training.
An active contour approach for segmentation of intra-retinal layers in optical coherence tomography images
Optical Coherence Tomography (OCT) is a non-invasive, depth-resolved imaging modality that has become a prominent ophthalmic diagnostic technique. We present a novel segmentation algorithm based on Chan-Vese\u27s energy-minimizing active contours to detect intra-retinal layers in OCT images. A multi-phase framework with a circular shape prior is adopted to model the boundaries of retinal layers and estimate shape parameters using least squares. We use a contextual scheme to balance the weight of different terms in the energy functional. The results from various synthetic experiments and segmentation results on rat OCT images are presented, demonstrating the strength of our method to detect the desired layers with sufficient accuracy even in the presence of intensity inhomogeneity. Our algorithm achieved an average Dice similarity coefficient of 0.84 over all segmented layers, and of 0.94 for the combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, which are critical layers for glaucomatous degeneration
Statistical methods for modeling the spatial structure on the visual field in glaucoma progression research
Diagnosing glaucoma progression is critical for limiting irreversible vision loss. A common method for assessing glaucoma progression uses a longitudinal series of visual fields (VF) acquired at regular intervals. VF data are characterized by a complex spatiotemporal structure due to the data generating process and ocular anatomy. Thus, advanced statistical methods are needed to make clinical determinations regarding progression status. In this dissertation, we introduce new modeling techniques that produce flexible spatial dependency structures within the framework of hierarchical Bayesian spatial models. The developed methodology is applied to VF data from the Vein Pulsation Study Trial in Glaucoma and the Lions Eye Institute trial registry.
In chapter 2, we work within the framework of boundary detection and introduce a spatiotemporal boundary detection model that allows the underlying anatomy of the optic disc to dictate localized spatial structure on the VF. We show that our new method provides insight into vision loss that improves diagnosis of glaucoma progression in actual glaucoma patients. Simulations are presented, showing the proposed methodology is preferred over existing spatial methods for VF data. An R package womblR is provided that implements the method.
Chapter 3 aims to introduce the modeling framework from chapter 2 to the ophthalmology community. An optimal form of the metric is established and compared with standard methods for assessing glaucoma progression using a statistical diagnostic framework. In particular, we demonstrate the added value of using the novel metric in addition to established prediction models based on standard operating characteristics. Finally, we detail the procedure for implementing our novel technique in the clinical setting.
In chapter 4, we present a framework that brings together vital aspects of glaucoma management, i) prediction of future VF sensitivities, ii) predicting the timing and location of future vision loss, iii) making clinical decisions regarding progression, and, iv) incorporation of anatomical information to create plausible data-generating models. We show that our method improves prediction and estimation of progression, and simulations are presented, showing the proposed methodology is preferred over existing models for VF data. An R package called spCP is provided that implements the method.Doctor of Philosoph