Detection and Classification of Diabetic Retinopathy Pathologies in Fundus Images

Diabetic Retinopathy (DR) is a disease that affects up to 80% of diabetics around the world. It is the second greatest cause of blindness in the Western world, and one of the leading causes of blindness in the U.S. Many studies have demonstrated that early treatment can reduce the number of sight-threatening DR cases, mitigating the medical and economic impact of the disease. Accurate, early detection of eye disease is important because of its potential to reduce rates of blindness worldwide. Retinal photography for DR has been promoted for decades for its utility in both disease screening and clinical research studies. In recent years, several research centers have presented systems to detect pathology in retinal images. However, these approaches apply specialized algorithms to detect specific types of lesion in the retina. In order to detect multiple lesions, these systems generally implement multiple algorithms. Furthermore, some of these studies evaluate their algorithms on a single dataset, thus avoiding potential problems associated with the differences in fundus imaging devices, such as camera resolution. These methodologies primarily employ bottom-up approaches, in which the accurate segmentation of all the lesions in the retina is the basis for correct determination. A disadvantage of bottom-up approaches is that they rely on the accurate segmentation of all lesions in order to measure performance. On the other hand, top-down approaches do not depend on the segmentation of specific lesions. Thus, top-down methods can potentially detect abnormalities not explicitly used in their training phase. A disadvantage of these methods is that they cannot identify specific pathologies and require large datasets to build their training models. In this dissertation, I merged the advantages of the top-down and bottom-up approaches to detect DR with high accuracy. First, I developed an algorithm based on a top-down approach to detect abnormalities in the retina due to DR. By doing so, I was able to evaluate DR pathologies other than microaneurysms and exudates, which are the main focus of most current approaches. In addition, I demonstrated good generalization capacity of this algorithm by applying it to other eye diseases, such as age-related macular degeneration. Due to the fact that high accuracy is required for sight-threatening conditions, I developed two bottom-up approaches, since it has been proven that bottom-up approaches produce more accurate results than top-down approaches for particular structures. Consequently, I developed an algorithm to detect exudates in the macula. The presence of this pathology is considered to be a surrogate for clinical significant macular edema (CSME), a sight-threatening condition of DR. The analysis of the optic disc is usually not taken into account in DR screening systems. However, there is a pathology called neovascularization that is present in advanced stages of DR, making its detection of crucial clinical importance. In order to address this problem, I developed an algorithm to detect neovascularization in the optic disc. These algorithms are based on amplitude-modulation and frequency-modulation (AM-FM) representations, morphological image processing methods, and classification algorithms. The methods were tested on a diverse set of large databases and are considered to be the state-of the art in this field

A Review: Person Identification using Retinal Fundus Images

In this paper a review on biometric person identification has been discussed using features from retinal fundus image. Retina recognition is claimed to be the best person identification method among the biometric recognition systems as the retina is practically impossible to forge. It is found to be most stable, reliable and most secure among all other biometric systems. Retina inherits the property of uniqueness and stability. The features used in the recognition process are either blood vessel features or non-blood vessel features. But the vascular pattern is the most prominent feature utilized by most of the researchers for retina based person identification. Processes involved in this authentication system include pre-processing, feature extraction and feature matching. Bifurcation and crossover points are widely used features among the blood vessel features. Non-blood vessel features include luminance, contrast, and corner points etc. This paper summarizes and compares the different retina based authentication system. Researchers have used publicly available databases such as DRIVE, STARE, VARIA, RIDB, ARIA, AFIO, DRIDB, and SiMES for testing their methods. Various quantitative measures such as accuracy, recognition rate, false rejection rate, false acceptance rate, and equal error rate are used to evaluate the performance of different algorithms. DRIVE database provides 100\% recognition for most of the methods. Rest of the database the accuracy of recognition is more than 90\%

Towards PACE-CAD Systems

Despite phenomenal advancements in the availability of medical image datasets and the development of modern classification algorithms, Computer-Aided Diagnosis (CAD) has had limited practical exposure in the real-world clinical workflow. This is primarily because of the inherently demanding and sensitive nature of medical diagnosis that can have far-reaching and serious repercussions in case of misdiagnosis. In this work, a paradigm called PACE (Pragmatic, Accurate, Confident, & Explainable) is presented as a set of some of must-have features for any CAD. Diagnosis of glaucoma using Retinal Fundus Images (RFIs) is taken as the primary use case for development of various methods that may enrich an ordinary CAD system with PACE. However, depending on specific requirements for different methods, other application areas in ophthalmology and dermatology have also been explored. Pragmatic CAD systems refer to a solution that can perform reliably in day-to-day clinical setup. In this research two, of possibly many, aspects of a pragmatic CAD are addressed. Firstly, observing that the existing medical image datasets are small and not representative of images taken in the real-world, a large RFI dataset for glaucoma detection is curated and published. Secondly, realising that a salient attribute of a reliable and pragmatic CAD is its ability to perform in a range of clinically relevant scenarios, classification of 622 unique cutaneous diseases in one of the largest publicly available datasets of skin lesions is successfully performed. Accuracy is one of the most essential metrics of any CAD system's performance. Domain knowledge relevant to three types of diseases, namely glaucoma, Diabetic Retinopathy (DR), and skin lesions, is industriously utilised in an attempt to improve the accuracy. For glaucoma, a two-stage framework for automatic Optic Disc (OD) localisation and glaucoma detection is developed, which marked new state-of-the-art for glaucoma detection and OD localisation. To identify DR, a model is proposed that combines coarse-grained classifiers with fine-grained classifiers and grades the disease in four stages with respect to severity. Lastly, different methods of modelling and incorporating metadata are also examined and their effect on a model's classification performance is studied. Confidence in diagnosing a disease is equally important as the diagnosis itself. One of the biggest reasons hampering the successful deployment of CAD in the real-world is that medical diagnosis cannot be readily decided based on an algorithm's output. Therefore, a hybrid CNN architecture is proposed with the convolutional feature extractor trained using point estimates and a dense classifier trained using Bayesian estimates. Evaluation on 13 publicly available datasets shows the superiority of this method in terms of classification accuracy and also provides an estimate of uncertainty for every prediction. Explainability of AI-driven algorithms has become a legal requirement after Europe’s General Data Protection Regulations came into effect. This research presents a framework for easy-to-understand textual explanations of skin lesion diagnosis. The framework is called ExAID (Explainable AI for Dermatology) and relies upon two fundamental modules. The first module uses any deep skin lesion classifier and performs detailed analysis on its latent space to map human-understandable disease-related concepts to the latent representation learnt by the deep model. The second module proposes Concept Localisation Maps, which extend Concept Activation Vectors by locating significant regions corresponding to a learned concept in the latent space of a trained image classifier. This thesis probes many viable solutions to equip a CAD system with PACE. However, it is noted that some of these methods require specific attributes in datasets and, therefore, not all methods may be applied on a single dataset. Regardless, this work anticipates that consolidating PACE into a CAD system can not only increase the confidence of medical practitioners in such tools but also serve as a stepping stone for the further development of AI-driven technologies in healthcare

Structure analysis and lesion detection from retinal fundus images

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Ocular pathology is one of the main health problems worldwide. The number of people with retinopathy symptoms has increased considerably in recent years. Early adequate treatment has demonstrated to be effective to avoid the loss of the vision. The analysis of fundus images is a non intrusive option for periodical retinal screening. Different models designed for the analysis of retinal images are based on supervised methods, which require of hand labelled images and processing time as part of the training stage. On the other hand most of the methods have been designed under the basis of specific characteristics of the retinal images (e.g. field of view, resolution). This compromises its performance to a reduce group of retinal image with similar features. For these reasons an unsupervised model for the analysis of retinal image is required, a model that can work without human supervision or interaction. And that is able to perform on retinal images with different characteristics. In this research, we have worked on the development of this type of model. The system locates the eye structures (e.g. optic disc and blood vessels) as first step. Later, these structures are masked out from the retinal image in order to create a clear field to perform the lesion detection. We have selected the Graph Cut technique as a base to design the retinal structures segmentation methods. This selection allows incorporating prior knowledge to constraint the searching for the optimal segmentation. Different link weight assignments were formulated in order to attend the specific needs of the retinal structures (e.g. shape). This research project has put to work together the fields of image processing and ophthalmology to create a novel system that contribute significantly to the state of the art in medical image analysis. This new knowledge provides a new alternative to address the analysis of medical images and opens a new panorama for researchers exploring this research area.Mexican National Council of Science and Technolog

Human Retina Based Identification System Using Gabor Filters and GDA Technique

A biometric authentication system provides an automatic person authentication based on some characteristic features possessed by the individual. Among all other biometrics, human retina is a secure and reliable source of person recognition as it is unique, universal, lies at the back of the eyeball and hence it is unforgeable. The process of authentication mainly includes pre-processing, feature extraction and then features matching and classification. Also authentication systems are mainly appointed in verification and identification mode according to the specific application. In this paper, preprocessing and image enhancement stages involve several steps to highlight interesting features in retinal images. The feature extraction stage is accomplished using a bank of Gabor filter with number of orientations and scales. Generalized Discriminant Analysis (GDA) technique has been used to reduce the size of feature vectors and enhance the performance of proposed algorithm. Finally, classification is accomplished using k-nearest neighbor (KNN) classifier to determine the identity of the genuine user or reject the forged one as the proposed method operates in identification mode. The main contribution in this paper is using Generalized Discriminant Analysis (GDA) technique to address ‘curse of dimensionality’ problem. GDA is a novel method used in the area of retina recognition

Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies.

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost

Cotton Wool Spots in Eye Fundus Scope

Diabetes mellitus é uma doença com um impacto significativo na saúde pública. Trata-se de uma alteração do metabolismo de hidratos de carbono, gorduras e proteínas que são resultado de uma deficiência ou ausência total de secreção/resistência à insulina por parte das células beta do pâncreas. Existem 3 tipos de diabetes, o denominado tipo 1 em que o doente é dependente de insulina, o tipo 2 em que o doente é dependente de insulina e a diabetes gestacional que aparece durante a fase de gravidez. A retinopatia diabética é uma complicação que pode resultar em cegueira. Se for detetada numa fase inicial, pode ser tratada por cirurgia a laser. No entanto, é dificil deteta-la numa fase inicial, uma vez que progride sem sintomas até ocorrer perda de visão de forma irreversível. Assim, se podermos detetar / encontrar exudados algodonosos no fundo de olho utilizando reconhecimento de imagem, anotação automática, sistemas de apoio à decisão de avaliação do risco, conjugados com uma aplicação móvel que permita a aquisição de imagens de fundo de olho, poderemos detetar mais cedo e tratar, evitando o risco cegueira do paciente. Este projeto tem como objetivo desenvolver uma aplicação smartphone baseada em algoritmos de baixo custo, que podem ser altamente eficientes nas imagens de baixa qualidade provenientes da câmara de um smartphone, que pode ser usada como um sistema de apoio à decisão. Este sistema também pode ser extendido a outras doenças oculares, como uma ferramenta útil para o rastreio de saúde ocular nos países em desenvolvimento, reforçar a proximidade dos programas de rastreio para a população. Os principais objetivos são desenvolver sistema fiável de apoio à decisão, considerando exudados algodonosos, juntamente com pontos vermelhos, em vez do sistema actualmente em uso em Portugal, que considera apenas os pontos vermelhos. O número casos Retinopatia Diabética em todo o mundo justifica o desenvolvimento de um sistema de suporte à decisão automatizado para triagem rápida e de baixo custo da Retinopatia Diabética.Diabetes mellitus é uma doença com um impacto significativo na saúde pública. Trata-se de uma alteração do metabolismo de hidratos de carbono, gorduras e proteínas que são resultado de uma deficiência ou ausência total de secreção/resistência à insulina por parte das células beta do pâncreas. Existem 3 tipos de diabetes, o denominado tipo 1 em que o doente é dependente de insulina, o tipo 2 em que o doente é dependente de insulina e a diabetes gestacional que aparece durante a fase de gravidez. A retinopatia diabética é uma complicação que pode resultar em cegueira. Se for detetada numa fase inicial, pode ser tratada por cirurgia a laser. No entanto, é dificil deteta-la numa fase inicial, uma vez que progride sem sintomas até ocorrer perda de visão de forma irreversível. Assim, se podermos detetar / encontrar exudados algodonosos no fundo de olho utilizando reconhecimento de imagem, anotação automática, sistemas de apoio à decisão de avaliação do risco, conjugados com uma aplicação móvel que permita a aquisição de imagens de fundo de olho, poderemos detetar mais cedo e tratar, evitando o risco cegueira do paciente. Este projeto tem como objetivo desenvolver uma aplicação smartphone baseada em algoritmos de baixo custo, que podem ser altamente eficientes nas imagens de baixa qualidade provenientes da câmara de um smartphone, que pode ser usada como um sistema de apoio à decisão. Este sistema também pode ser extendido a outras doenças oculares, como uma ferramenta útil para o rastreio de saúde ocular nos países em desenvolvimento, reforçar a proximidade dos programas de rastreio para a população. Os principais objetivos são desenvolver sistema fiável de apoio à decisão, considerando exudados algodonosos, juntamente com pontos vermelhos, em vez do sistema actualmente em uso em Portugal, que considera apenas os pontos vermelhos. O número casos Retinopatia Diabética em todo o mundo justifica o desenvolvimento de um sistema de suporte à decisão automatizado para triagem rápida e de baixo custo da Retinopatia Diabética.Diabetes mellitus is a disease with significant impact in public health. It is a complex disorder of carbohydrate, fat and protein metabolism that is a result of a deficiency, or complete lack of insulin secretion by the Beta cells of pancreas, or resistance to Insulin. There are 3 types of diabetes, namely type 1 where the patient is insulin-dependent, type 2 where the patient is non insulin-dependent and gestational diabetes that appears during the pregnancy phase.Retinopathy is a diabetes complication that can result in blindness. If detected in an early stage, it can be treated by laser surgery. However its early detection is frequently missed, since it progresses without symptoms until irreversible vision loss occurs.So if we can detect/find cotton wool spots in eye fundus scope by using image recognition, automatic annotation, decision-support systems for risk assessment, conjugate with a mobile app acquiring eye fundus images, we might detect early and treat avoiding patient blindness risk.This project aims to develop a smartphone-based on low computational-cost algorithms, which can be highly efficient in the lower quality images of the smartphone camera, that can be used as a decision-support system. This system may also be extended to other eye diseases, as an useful tool for eye health screening in developing countries and enhance the proximity of screening programs to the population.The main expected contribution is to develop a good decision-support system, considering cotton wool spots, together with red dots, instead of the actual system in use in Portugal which only considers red dots. The number of Diabetic Retinopathy cases worldwide justifies the development of an automated decision-support system for quick and cost effective screening of Diabetic Retinopathy

Deep Learning Techniques for Automated Analysis and Processing of High Resolution Medical Imaging

Programa Oficial de Doutoramento en Computación . 5009V01[Abstract] Medical imaging plays a prominent role in modern clinical practice for numerous medical specialties. For instance, in ophthalmology, different imaging techniques are commonly used to visualize and study the eye fundus. In this context, automated image analysis methods are key towards facilitating the early diagnosis and adequate treatment of several diseases. Nowadays, deep learning algorithms have already demonstrated a remarkable performance for different image analysis tasks. However, these approaches typically require large amounts of annotated data for the training of deep neural networks. This complicates the adoption of deep learning approaches, especially in areas where large scale annotated datasets are harder to obtain, such as in medical imaging. This thesis aims to explore novel approaches for the automated analysis of medical images, particularly in ophthalmology. In this regard, the main focus is on the development of novel deep learning-based approaches that do not require large amounts of annotated training data and can be applied to high resolution images. For that purpose, we have presented a novel paradigm that allows to take advantage of unlabeled complementary image modalities for the training of deep neural networks. Additionally, we have also developed novel approaches for the detailed analysis of eye fundus images. In that regard, this thesis explores the analysis of relevant retinal structures as well as the diagnosis of different retinal diseases. In general, the developed algorithms provide satisfactory results for the analysis of the eye fundus, even when limited annotated training data is available.[Resumen] Las técnicas de imagen tienen un papel destacado en la práctica clínica moderna de numerosas especialidades médicas. Por ejemplo, en oftalmología es común el uso de diferentes técnicas de imagen para visualizar y estudiar el fondo de ojo. En este contexto, los métodos automáticos de análisis de imagen son clave para facilitar el diagnóstico precoz y el tratamiento adecuado de diversas enfermedades. En la actualidad, los algoritmos de aprendizaje profundo ya han demostrado un notable rendimiento en diferentes tareas de análisis de imagen. Sin embargo, estos métodos suelen necesitar grandes cantidades de datos etiquetados para el entrenamiento de las redes neuronales profundas. Esto complica la adopción de los métodos de aprendizaje profundo, especialmente en áreas donde los conjuntos masivos de datos etiquetados son más difíciles de obtener, como es el caso de la imagen médica. Esta tesis tiene como objetivo explorar nuevos métodos para el análisis automático de imagen médica, concretamente en oftalmología. En este sentido, el foco principal es el desarrollo de nuevos métodos basados en aprendizaje profundo que no requieran grandes cantidades de datos etiquetados para el entrenamiento y puedan aplicarse a imágenes de alta resolución. Para ello, hemos presentado un nuevo paradigma que permite aprovechar modalidades de imagen complementarias no etiquetadas para el entrenamiento de redes neuronales profundas. Además, también hemos desarrollado nuevos métodos para el análisis en detalle de las imágenes del fondo de ojo. En este sentido, esta tesis explora el análisis de estructuras retinianas relevantes, así como el diagnóstico de diferentes enfermedades de la retina. En general, los algoritmos desarrollados proporcionan resultados satisfactorios para el análisis de las imágenes de fondo de ojo, incluso cuando la disponibilidad de datos de entrenamiento etiquetados es limitada.[Resumo] As técnicas de imaxe teñen un papel destacado na práctica clínica moderna de numerosas especialidades médicas. Por exemplo, en oftalmoloxía é común o uso de diferentes técnicas de imaxe para visualizar e estudar o fondo de ollo. Neste contexto, os métodos automáticos de análises de imaxe son clave para facilitar o diagn ostico precoz e o tratamento adecuado de diversas enfermidades. Na actualidade, os algoritmos de aprendizaxe profunda xa demostraron un notable rendemento en diferentes tarefas de análises de imaxe. Con todo, estes métodos adoitan necesitar grandes cantidades de datos etiquetos para o adestramento das redes neuronais profundas. Isto complica a adopción dos métodos de aprendizaxe profunda, especialmente en áreas onde os conxuntos masivos de datos etiquetados son máis difíciles de obter, como é o caso da imaxe médica. Esta tese ten como obxectivo explorar novos métodos para a análise automática de imaxe médica, concretamente en oftalmoloxía. Neste sentido, o foco principal é o desenvolvemento de novos métodos baseados en aprendizaxe profunda que non requiran grandes cantidades de datos etiquetados para o adestramento e poidan aplicarse a imaxes de alta resolución. Para iso, presentamos un novo paradigma que permite aproveitar modalidades de imaxe complementarias non etiquetadas para o adestramento de redes neuronais profundas. Ademais, tamén desenvolvemos novos métodos para a análise en detalle das imaxes do fondo de ollo. Neste sentido, esta tese explora a análise de estruturas retinianas relevantes, así como o diagnóstico de diferentes enfermidades da retina. En xeral, os algoritmos desenvolvidos proporcionan resultados satisfactorios para a análise das imaxes de fondo de ollo, mesmo cando a dispoñibilidade de datos de adestramento etiquetados é limitada

Computational assessment of the retinal vascular tortuosity integrating domain-related information

[Abstract] The retinal vascular tortuosity presents a valuable potential as a clinical biomarker of many relevant vascular and systemic diseases. Commonly, the existent approaches face the tortuosity quantification by means of fully mathematical representations of the vessel segments. However, the specialists, based on their diagnostic experience, commonly analyze additional domain-related information that is not represented in these mathematical metrics of reference. In this work, we propose a novel computational tortuosity metric that outperforms the mathematical metrics of reference also incorporating anatomical properties of the fundus image such as the distinction between arteries and veins, the distance to the optic disc, the distance to the fovea, and the vessel caliber. The evaluation of its prognostic performance shows that the integration of the anatomical factors provides an accurate tortuosity assessment that is more adjusted to the specialists’ perception.Instituto de Salud Carlos II; DTS18/00136Ministerio de Ciencia, Innovación y Universidades; DPI2015-69948-RMinisterio de Ciencia, Innovación y Universidades; RTI2018-095894-B-I00Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-04