Fundus image analysis for automatic screening of ophthalmic pathologies

En los ultimos años el número de casos de ceguera se ha reducido significativamente. A pesar de este hecho, la Organización Mundial de la Salud estima que un 80% de los casos de pérdida de visión (285 millones en 2010) pueden ser evitados si se diagnostican en sus estadios más tempranos y son tratados de forma efectiva. Para cumplir esta propuesta se pretende que los servicios de atención primaria incluyan un seguimiento oftalmológico de sus pacientes así como fomentar campañas de cribado en centros proclives a reunir personas de alto riesgo. Sin embargo, estas soluciones exigen una alta carga de trabajo de personal experto entrenado en el análisis de los patrones anómalos propios de cada enfermedad. Por lo tanto, el desarrollo de algoritmos para la creación de sistemas de cribado automáticos juga un papel vital en este campo. La presente tesis persigue la identificacion automática del daño retiniano provocado por dos de las patologías más comunes en la sociedad actual: la retinopatía diabética (RD) y la degenaración macular asociada a la edad (DMAE). Concretamente, el objetivo final de este trabajo es el desarrollo de métodos novedosos basados en la extracción de características de la imagen de fondo de ojo y clasificación para discernir entre tejido sano y patológico. Además, en este documento se proponen algoritmos de pre-procesado con el objetivo de normalizar la alta variabilidad existente en las bases de datos publicas de imagen de fondo de ojo y eliminar la contribución de ciertas estructuras retinianas que afectan negativamente en la detección del daño retiniano. A diferencia de la mayoría de los trabajos existentes en el estado del arte sobre detección de patologías en imagen de fondo de ojo, los métodos propuestos a lo largo de este manuscrito evitan la necesidad de segmentación de las lesiones o la generación de un mapa de candidatos antes de la fase de clasificación. En este trabajo, Local binary patterns, perfiles granulométricos y la dimensión fractal se aplican de manera local para extraer información de textura, morfología y tortuosidad de la imagen de fondo de ojo. Posteriormente, esta información se combina de diversos modos formando vectores de características con los que se entrenan avanzados métodos de clasificación formulados para discriminar de manera óptima entre exudados, microaneurismas, hemorragias y tejido sano. Mediante diversos experimentos, se valida la habilidad del sistema propuesto para identificar los signos más comunes de la RD y DMAE. Para ello se emplean bases de datos públicas con un alto grado de variabilidad sin exlcuir ninguna imagen. Además, la presente tesis también cubre aspectos básicos del paradigma de deep learning. Concretamente, se presenta un novedoso método basado en redes neuronales convolucionales (CNNs). La técnica de transferencia de conocimiento se aplica mediante el fine-tuning de las arquitecturas de CNNs más importantes en el estado del arte. La detección y localización de exudados mediante redes neuronales se lleva a cabo en los dos últimos experimentos de esta tesis doctoral. Cabe destacar que los resultados obtenidos mediante la extracción de características "manual" y posterior clasificación se comparan de forma objetiva con las predicciones obtenidas por el mejor modelo basado en CNNs. Los prometedores resultados obtenidos en esta tesis y el bajo coste y portabilidad de las cámaras de adquisión de imagen de retina podrían facilitar la incorporación de los algoritmos desarrollados en este trabajo en un sistema de cribado automático que ayude a los especialistas en la detección de patrones anomálos característicos de las dos enfermedades bajo estudio: RD y DMAE.In last years, the number of blindness cases has been significantly reduced. Despite this promising news, the World Health Organisation estimates that 80% of visual impairment (285 million cases in 2010) could be avoided if diagnosed and treated early. To accomplish this purpose, eye care services need to be established in primary health and screening campaigns should be a common task in centres with people at risk. However, these solutions entail a high workload for trained experts in the analysis of the anomalous patterns of each eye disease. Therefore, the development of algorithms for automatic screening system plays a vital role in this field. This thesis focuses on the automatic identification of the retinal damage provoked by two of the most common pathologies in the current society: diabetic retinopathy (DR) and age-related macular degeneration (AMD). Specifically, the final goal of this work is to develop novel methods, based on fundus image description and classification, to characterise the healthy and abnormal tissue in the retina background. In addition, pre-processing algorithms are proposed with the aim of normalising the high variability of fundus images and removing the contribution of some retinal structures that could hinder in the retinal damage detection. In contrast to the most of the state-of-the-art works in damage detection using fundus images, the methods proposed throughout this manuscript avoid the necessity of lesion segmentation or the candidate map generation before the classification stage. Local binary patterns, granulometric profiles and fractal dimension are locally computed to extract texture, morphological and roughness information from retinal images. Different combinations of this information feed advanced classification algorithms formulated to optimally discriminate exudates, microaneurysms, haemorrhages and healthy tissues. Through several experiments, the ability of the proposed system to identify DR and AMD signs is validated using different public databases with a large degree of variability and without image exclusion. Moreover, this thesis covers the basics of the deep learning paradigm. In particular, a novel approach based on convolutional neural networks is explored. The transfer learning technique is applied to fine-tune the most important state-of-the-art CNN architectures. Exudate detection and localisation tasks using neural networks are carried out in the last two experiments of this thesis. An objective comparison between the hand-crafted feature extraction and classification process and the prediction models based on CNNs is established. The promising results of this PhD thesis and the affordable cost and portability of retinal cameras could facilitate the further incorporation of the developed algorithms in a computer-aided diagnosis (CAD) system to help specialists in the accurate detection of anomalous patterns characteristic of the two diseases under study: DR and AMD.En els últims anys el nombre de casos de ceguera s'ha reduït significativament. A pesar d'este fet, l'Organització Mundial de la Salut estima que un 80% dels casos de pèrdua de visió (285 milions en 2010) poden ser evitats si es diagnostiquen en els seus estadis més primerencs i són tractats de forma efectiva. Per a complir esta proposta es pretén que els servicis d'atenció primària incloguen un seguiment oftalmològic dels seus pacients així com fomentar campanyes de garbellament en centres regentats per persones d'alt risc. No obstant això, estes solucions exigixen una alta càrrega de treball de personal expert entrenat en l'anàlisi dels patrons anòmals propis de cada malaltia. Per tant, el desenrotllament d'algoritmes per a la creació de sistemes de garbellament automàtics juga un paper vital en este camp. La present tesi perseguix la identificació automàtica del dany retiniano provocat per dos de les patologies més comunes en la societat actual: la retinopatia diabètica (RD) i la degenaración macular associada a l'edat (DMAE) . Concretament, l'objectiu final d'este treball és el desenrotllament de mètodes novedodos basats en l'extracció de característiques de la imatge de fons d'ull i classificació per a discernir entre teixit sa i patològic. A més, en este document es proposen algoritmes de pre- processat amb l'objectiu de normalitzar l'alta variabilitat existent en les bases de dades publiques d'imatge de fons d'ull i eliminar la contribució de certes estructures retinianas que afecten negativament en la detecció del dany retiniano. A diferència de la majoria dels treballs existents en l'estat de l'art sobre detecció de patologies en imatge de fons d'ull, els mètodes proposats al llarg d'este manuscrit eviten la necessitat de segmentació de les lesions o la generació d'un mapa de candidats abans de la fase de classificació. En este treball, Local binary patterns, perfils granulometrics i la dimensió fractal s'apliquen de manera local per a extraure informació de textura, morfologia i tortuositat de la imatge de fons d'ull. Posteriorment, esta informació es combina de diversos modes formant vectors de característiques amb els que s'entrenen avançats mètodes de classificació formulats per a discriminar de manera òptima entre exsudats, microaneurismes, hemorràgies i teixit sa. Per mitjà de diversos experiments, es valida l'habilitat del sistema proposat per a identificar els signes més comuns de la RD i DMAE. Per a això s'empren bases de dades públiques amb un alt grau de variabilitat sense exlcuir cap imatge. A més, la present tesi també cobrix aspectes bàsics del paradigma de deep learning. Concretament, es presenta un nou mètode basat en xarxes neuronals convolucionales (CNNs) . La tècnica de transferencia de coneixement s'aplica per mitjà del fine-tuning de les arquitectures de CNNs més importants en l'estat de l'art. La detecció i localització d'exudats per mitjà de xarxes neuronals es du a terme en els dos últims experiments d'esta tesi doctoral. Cal destacar que els resultats obtinguts per mitjà de l'extracció de característiques "manual" i posterior classificació es comparen de forma objectiva amb les prediccions obtingudes pel millor model basat en CNNs. Els prometedors resultats obtinguts en esta tesi i el baix cost i portabilitat de les cambres d'adquisión d'imatge de retina podrien facilitar la incorporació dels algoritmes desenrotllats en este treball en un sistema de garbellament automàtic que ajude als especialistes en la detecció de patrons anomálos característics de les dos malalties baix estudi: RD i DMAE.Colomer Granero, A. (2018). Fundus image analysis for automatic screening of ophthalmic pathologies [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/99745TESI

Current roles of artificial intelligence in ophthalmology

Artificial intelligence (AI) studies are increasingly reporting successful results in the diagnosis and prognosis prediction of ophthalmological diseases as well as systemic disorders. The goal of this review is to detail how AI can be utilized in making diagnostic predictions to enhance the clinical setting. It is crucial to keep improving methods that emphasize clarity in AI models. This makes it possible to evaluate the information obtained from ocular imaging and easily incorporate it into therapeutic decision-making procedures. This will contribute to the wider acceptance and adoption of AI-based ocular imaging in healthcare settings combining advanced machine learning and deep learning techniques with new developments. Multiple studies were reviewed and evaluated, including AI-based algorithms, retinal images, fundus and optic nerve head (ONH) photographs, and extensive expert reviews. In these studies, carried out in various countries and laboratories of the world, it is seen those complex diagnoses, which can be detected systemic diseases from ophthalmological images, can be made much faster and with higher predictability, accuracy, sensitivity, and specificity, in addition to ophthalmological diseases, by comparing large numbers of images and teaching them to the computer. It is now clear that it can be taken advantage of AI to achieve diagnostic certainty. Collaboration between the fields of medicine and engineering foresees promising advances in improving the predictive accuracy and precision of future medical diagnoses achieved by training machines with this information. However, it is important to keep in mind that each new development requires new additions or updates to various social, psychological, ethical, and legal regulations

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

CLASSIFICATION OF IMAGES BASED ON PIXELS THAT REPRESENT A SMALL PART OF THE SCENE. A CASE APPLIED TO MICROANEURYSMS IN FUNDUS RETINA IMAGES

Convolutional Neural Networks (CNNs), the state of the art in image classification, have proven to be as effective as an ophthalmologist, when detecting Referable Diabetic Retinopathy (RDR). Having a size of less than 1\% of the total image, microaneurysms are early lesions in DR that are difficult to classify. The purpose of this thesis is to improve the accuracy of detection of microaneurysms using a model that includes two CNNs with different input image sizes, 60x60 and 420x420 pixels. These models were trained using the Kaggle and Messidor datasets and tested independently against the Kaggle dataset, showing a sensitivity of 95\% and 91\%, a specificity of 98\% and 93\%, and an area under the Receiver Operating Characteristics curve of 0.98 and 0.96, respectively, in the sliced images. Furthermore, by combining these trained models, there was a reduction of false positives for complete images by about 50\% and a sensitivity of 96\% when tested against the DIARETDB1 dataset . In addition, a powerful image pre-processing procedure was implemented, which included adjusting luminescence and color reduction, improving not only images for annotations, but also decreasing the number of epochs during training. Finally, a novel feedback operation that re-sent batches not classified as well as expected, increased the accuracy of the CNN 420 x 420 pixel input model

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

An in vivo investigation of choroidal vasculature in age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world. Whilst the pathogenesis is complex and not fully understood, changes to the choroidal vasculature in AMD have been demonstrated using histology. Advances in imaging technology, particularly long-wavelength optical coherence tomography (OCT), allow in vivo visualisation and investigation of this structure. The aim of this work is to determine whether changes to the choroidal vasculature are detectable in AMD using in vivo imaging. This was achieved through the evaluation of parameters for quantifying the structure, and the application of a machine learning approach to automated disease severity classification, based on choroidal appearance. Participants with early AMD (n=25), neovascular AMD (nAMD; n=25), and healthy controls (n=25) underwent imaging with a non-commercial long-wavelength (λc=1040 nm) OCT device. Subfoveal choroidal thickness, choroidal area, and luminal area were significantly lower in the nAMD group than the healthy and early AMD groups, whilst vessel ratio was significantly greater (P<0.05 in all cases). There was no significant difference in visible vessel diameter, choroidal vascularity index, luminal area ratio, or luminal perimeter ratio between the groups. No significant differences were found between the healthy and early AMD groups for any of the eight vascular parameters assessed. Classification of the disease groups based on choroidal OCT images was demonstrated using machine learning techniques. Textural features within the images were extracted using Gabor filters, and K-nearest neighbour, support vector machine, and random forest classifiers were assessed for this classification task. Textural changes were most pronounced in late-stage disease, although attribution to pathology or pharmacological intervention (anti-VEGF treatment) was not possible. Changes were also discernible in the early AMD group, suggesting sensitivity of this approach to detecting vascular involvement in early disease. In conclusion, structural changes to the choroidal vasculature in AMD are detectable in vivo using OCT imaging, demonstrated with both manual and automated analysis techniques. Whilst changes were most prominent in late-stage disease, subtle structural changes in early AMD were identified with texture analysis, warranting further investigation to improve our understanding of choroidal involvement in the pathogenesis of early AMD

Characterization of age-related ocular diseases in OCT images through deep learning techniques

[Abstract]: Age-Related Macular Degeneration (AMD) is the main cause of severe visual impairment and blindness in Europe, and its prevalence is expected to increase worldwide due to population aging. Optical Coherence Tomography (OCT) is a noninvasive retinal imaging technique that has become the standard of care in the diagnosis and monitoring of late AMD, where the great majority of severe symptoms are manifested. Neovascular late AMD, where new pathological blood vessels are formed that may leak fluid, often results in relatively rapid vision loss. Treatment exists for neovascular AMD, such that its detection and characterization plays a key role in patient outcomes. This project applies deep learning techniques to the task of AMD characterization. To do so, a data set of OCT scans labeled as to the presence of fluid and neovascularisation is used to train deep convolutional networks. Analysis of this initial experiment produced two hypotheses of performance limiting factors: intra-expert variability and data scarcity. The former was addressed through the development of a machine-assisted review process based on the Class Activation Mapping (CAM) interpretability technique. A small blinded trial was favorable to the methodology. The latter resulted in the adaptation of a large public data set to explore domain-specific transfer learning.[Resumo]: A Dexeneración Macular Asociada á Idade (DMAI) é a principal causa de discapacidade visual severa e cegueira en Europa, e espérase que a súa prevalencia aumente a nivel mundial debido ó envellecemento poboacional. A Tomografía de Coherencia Óptica (TCO) é un método non invasivo de imaxe retiniana que se converteu no estándar no diagnóstico e monitorización da DMAI tardía, onde se manifestan a maioría de síntomas graves. A DMAI tardía neovascular, onde se forman novos vasos sanguíneos patolóxicos que poden derramar fluído, a miúdo resulta en perda de visión de forma relativamente repentina. Existen tratamentos para a DMAI neovascular, de modo que a súa detección e caracterización xoga un papel crucial no prognóstico dos pacientes. Este proxecto aplica técnicas de aprendizaxe profunda á tarefa de caracterización de DMAI. Con ese fin, un conxunto de datos de TCO anotado en base á presenza de fluído e neovascularización foi empregado para entrenar redes convolucionais profundas. A análise deste experimento inicial produciu dúas hipóteses sobre factores que limitan o rendemento: a variabilidade intra-experto e a escaseza de datos. O primeiro foi afrontado mediante o desenvolvemento dun proceso de revisión de anotacións asistido por computadora, baseado na técnica de interpretabilidade Class Activation Mapping (CAM). Un pequeno estudo cego foi favorable á metodoloxía. A segunda hipótese resultou na adaptación dun gran conxunto de datos público para a exploración de transferencia de aprendizaxe específica ó dominio.Traballo fin de grao (UDC.FIC). Enxeñaría Informática. Curso 2021/202

Segmentation and Characterization of Small Retinal Vessels in Fundus Images Using the Tensor Voting Approach

RÉSUMÉ La rétine permet de visualiser facilement une partie du réseau vasculaire humain. Elle offre ainsi un aperçu direct sur le développement et le résultat de certaines maladies liées au réseau vasculaire dans son entier. Chaque complication visible sur la rétine peut avoir un impact sur la capacité visuelle du patient. Les plus petits vaisseaux sanguins sont parmi les premières structures anatomiques affectées par la progression d’une maladie, être capable de les analyser est donc crucial. Les changements dans l’état, l’aspect, la morphologie, la fonctionnalité, ou même la croissance des petits vaisseaux indiquent la gravité des maladies. Le diabète est une maladie métabolique qui affecte des millions de personnes autour du monde. Cette maladie affecte le taux de glucose dans le sang et cause des changements pathologiques dans différents organes du corps humain. La rétinopathie diabétique décrit l’en- semble des conditions et conséquences du diabète au niveau de la rétine. Les petits vaisseaux jouent un rôle dans le déclenchement, le développement et les conséquences de la rétinopa- thie. Dans les dernières étapes de cette maladie, la croissance des nouveaux petits vaisseaux, appelée néovascularisation, présente un risque important de provoquer la cécité. Il est donc crucial de détecter tous les changements qui ont lieu dans les petits vaisseaux de la rétine dans le but de caractériser les vaisseaux sains et les vaisseaux anormaux. La caractérisation en elle-même peut faciliter la détection locale d’une rétinopathie spécifique. La segmentation automatique des structures anatomiques comme le réseau vasculaire est une étape cruciale. Ces informations peuvent être fournies à un médecin pour qu’elles soient considérées lors de son diagnostic. Dans les systèmes automatiques d’aide au diagnostic, le rôle des petits vaisseaux est significatif. Ne pas réussir à les détecter automatiquement peut conduire à une sur-segmentation du taux de faux positifs des lésions rouges dans les étapes ultérieures. Les efforts de recherche se sont concentrés jusqu’à présent sur la localisation précise des vaisseaux de taille moyenne. Les modèles existants ont beaucoup plus de difficultés à extraire les petits vaisseaux sanguins. Les modèles existants ne sont pas robustes à la grande variance d’apparence des vaisseaux ainsi qu’à l’interférence avec l’arrière-plan. Les modèles de la littérature existante supposent une forme générale qui n’est pas suffisante pour s’adapter à la largeur étroite et la courbure qui caractérisent les petits vaisseaux sanguins. De plus, le contraste avec l’arrière-plan dans les régions des petits vaisseaux est très faible. Les méthodes de segmentation ou de suivi produisent des résultats fragmentés ou discontinus. Par ailleurs, la segmentation des petits vaisseaux est généralement faite aux dépends de l’amplification du bruit. Les modèles déformables sont inadéquats pour segmenter les petits vaisseaux. Les forces utilisées ne sont pas assez flexibles pour compenser le faible contraste, la largeur, et vii la variance des vaisseaux. Enfin, les approches de type apprentissage machine nécessitent un entraînement avec une base de données étiquetée. Il est très difficile d’obtenir ces bases de données dans le cas des petits vaisseaux. Cette thèse étend les travaux de recherche antérieurs en fournissant une nouvelle mé- thode de segmentation des petits vaisseaux rétiniens. La détection de ligne à échelles multiples (MSLD) est une méthode récente qui démontre une bonne performance de segmentation dans les images de la rétine, tandis que le vote tensoriel est une méthode proposée pour reconnecter les pixels. Une approche combinant un algorithme de détection de ligne et de vote tensoriel est proposée. L’application des détecteurs de lignes a prouvé son efficacité à segmenter les vais- seaux de tailles moyennes. De plus, les approches d’organisation perceptuelle comme le vote tensoriel ont démontré une meilleure robustesse en combinant les informations voisines d’une manière hiérarchique. La méthode de vote tensoriel est plus proche de la perception humain que d’autres modèles standards. Comme démontré dans ce manuscrit, c’est un outil pour segmenter les petits vaisseaux plus puissant que les méthodes existantes. Cette combinaison spécifique nous permet de surmonter les défis de fragmentation éprouvés par les méthodes de type modèle déformable au niveau des petits vaisseaux. Nous proposons également d’utiliser un seuil adaptatif sur la réponse de l’algorithme de détection de ligne pour être plus robuste aux images non-uniformes. Nous illustrons également comment une combinaison des deux méthodes individuelles, à plusieurs échelles, est capable de reconnecter les vaisseaux sur des distances variables. Un algorithme de reconstruction des vaisseaux est également proposé. Cette dernière étape est nécessaire car l’information géométrique complète est requise pour pouvoir utiliser la segmentation dans un système d’aide au diagnostic. La segmentation a été validée sur une base de données d’images de fond d’oeil à haute résolution. Cette base contient des images manifestant une rétinopathie diabétique. La seg- mentation emploie des mesures de désaccord standards et aussi des mesures basées sur la perception. En considérant juste les petits vaisseaux dans les images de la base de données, l’amélioration dans le taux de sensibilité que notre méthode apporte par rapport à la méthode standard de détection multi-niveaux de lignes est de 6.47%. En utilisant les mesures basées sur la perception, l’amélioration est de 7.8%. Dans une seconde partie du manuscrit, nous proposons également une méthode pour caractériser les rétines saines ou anormales. Certaines images contiennent de la néovascula- risation. La caractérisation des vaisseaux en bonne santé ou anormale constitue une étape essentielle pour le développement d’un système d’aide au diagnostic. En plus des défis que posent les petits vaisseaux sains, les néovaisseaux démontrent eux un degré de complexité encore plus élevé. Ceux-ci forment en effet des réseaux de vaisseaux à la morphologie com- plexe et inhabituelle, souvent minces et à fortes courbures. Les travaux existants se limitent viii à l’utilisation de caractéristiques de premier ordre extraites des petits vaisseaux segmentés. Notre contribution est d’utiliser le vote tensoriel pour isoler les jonctions vasculaires et d’uti- liser ces jonctions comme points d’intérêts. Nous utilisons ensuite une statistique spatiale de second ordre calculée sur les jonctions pour caractériser les vaisseaux comme étant sains ou pathologiques. Notre méthode améliore la sensibilité de la caractérisation de 9.09% par rapport à une méthode de l’état de l’art. La méthode développée s’est révélée efficace pour la segmentation des vaisseaux réti- niens. Des tenseurs d’ordre supérieur ainsi que la mise en œuvre d’un vote par tenseur via un filtrage orientable pourraient être étudiés pour réduire davantage le temps d’exécution et résoudre les défis encore présents au niveau des jonctions vasculaires. De plus, la caractéri- sation pourrait être améliorée pour la détection de la rétinopathie proliférative en utilisant un apprentissage supervisé incluant des cas de rétinopathie diabétique non proliférative ou d’autres pathologies. Finalement, l’incorporation des méthodes proposées dans des systèmes d’aide au diagnostic pourrait favoriser le dépistage régulier pour une détection précoce des rétinopathies et d’autres pathologies oculaires dans le but de réduire la cessité au sein de la population.----------ABSTRACT As an easily accessible site for the direct observation of the circulation system, human retina can offer a unique insight into diseases development or outcome. Retinal vessels are repre- sentative of the general condition of the whole systematic circulation, and thus can act as a "window" to the status of the vascular network in the whole body. Each complication on the retina can have an adverse impact on the patient’s sight. In this direction, small vessels’ relevance is very high as they are among the first anatomical structures that get affected as diseases progress. Moreover, changes in the small vessels’ state, appearance, morphology, functionality, or even growth indicate the severity of the diseases. This thesis will focus on the retinal lesions due to diabetes, a serious metabolic disease affecting millions of people around the world. This disorder disturbs the natural blood glucose levels causing various pathophysiological changes in different systems across the human body. Diabetic retinopathy is the medical term that describes the condition when the fundus and the retinal vessels are affected by diabetes. As in other diseases, small vessels play a crucial role in the onset, the development, and the outcome of the retinopathy. More importantly, at the latest stage, new small vessels, or neovascularizations, growth constitutes a factor of significant risk for blindness. Therefore, there is a need to detect all the changes that occur in the small retinal vessels with the aim of characterizing the vessels to healthy or abnormal. The characterization, in turn, can facilitate the detection of a specific retinopathy locally, like the sight-threatening proliferative diabetic retinopathy. Segmentation techniques can automatically isolate important anatomical structures like the vessels, and provide this information to the physician to assist him in the final decision. In comprehensive systems for the automatization of DR detection, small vessels role is significant as missing them early in a CAD pipeline might lead to an increase in the false positive rate of red lesions in subsequent steps. So far, the efforts have been concentrated mostly on the accurate localization of the medium range vessels. In contrast, the existing models are weak in case of the small vessels. The required generalization to adapt an existing model does not allow the approaches to be flexible, yet robust to compensate for the increased variability in the appearance as well as the interference with the background. So far, the current template models (matched filtering, line detection, and morphological processing) assume a general shape for the vessels that is not enough to approximate the narrow, curved, characteristics of the small vessels. Additionally, due to the weak contrast in the small vessel regions, the current segmentation and the tracking methods produce fragmented or discontinued results. Alternatively, the small vessel segmentation can be accomplished at the expense of x background noise magnification, in the case of using thresholding or the image derivatives methods. Furthermore, the proposed deformable models are not able to propagate a contour to the full extent of the vasculature in order to enclose all the small vessels. The deformable model external forces are ineffective to compensate for the low contrast, the low width, the high variability in the small vessel appearance, as well as the discontinuities. Internal forces, also, are not able to impose a global shape constraint to the contour that could be able to approximate the variability in the appearance of the vasculature in different categories of vessels. Finally, machine learning approaches require the training of a classifier on a labelled set. Those sets are difficult to be obtained, especially in the case of the smallest vessels. In the case of the unsupervised methods, the user has to predefine the number of clusters and perform an effective initialization of the cluster centers in order to converge to the global minimum. This dissertation expanded the previous research work and provides a new segmentation method for the smallest retinal vessels. Multi-scale line detection (MSLD) is a recent method that demonstrates good segmentation performance in the retinal images, while tensor voting is a method first proposed for reconnecting pixels. For the first time, we combined the line detection with the tensor voting framework. The application of the line detectors has been proved an effective way to segment medium-sized vessels. Additionally, perceptual organization approaches like tensor voting, demonstrate increased robustness by combining information coming from the neighborhood in a hierarchical way. Tensor voting is closer than standard models to the way human perception functions. As we show, it is a more powerful tool to segment small vessels than the existing methods. This specific combination allows us to overcome the apparent fragmentation challenge of the template methods at the smallest vessels. Moreover, we thresholded the line detection response adaptively to compensate for non-uniform images. We also combined the two individual methods in a multi-scale scheme in order to reconnect vessels at variable distances. Finally, we reconstructed the vessels from their extracted centerlines based on pixel painting as complete geometric information is required to be able to utilize the segmentation in a CAD system. The segmentation was validated on a high-resolution fundus image database that in- cludes diabetic retinopathy images of varying stages, using standard discrepancy as well as perceptual-based measures. When only the smallest vessels are considered, the improve- ments in the sensitivity rate for the database against the standard multi-scale line detection method is 6.47%. For the perceptual-based measure, the improvement is 7.8% against the basic method. The second objective of the thesis was to implement a method for the characterization of isolated retinal areas into healthy or abnormal cases. Some of the original images, from which xi these patches are extracted, contain neovascularizations. Investigation of image features for the vessels characterization to healthy or abnormal constitutes an essential step in the direction of developing CAD system for the automatization of DR screening. Given that the amount of data will significantly increase under CAD systems, the focus on this category of vessels can facilitate the referral of sight-threatening cases to early treatment. In addition to the challenges that small healthy vessels pose, neovessels demonstrate an even higher degree of complexity as they form networks of convolved, twisted, looped thin vessels. The existing work is limited to the use of first-order characteristics extracted from the small segmented vessels that limits the study of patterns. Our contribution is in using the tensor voting framework to isolate the retinal vascular junctions and in turn using those junctions as points of interests. Second, we exploited second-order statistics computed on the junction spatial distribution to characterize the vessels as healthy or neovascularizations. In fact, the second-order spatial statistics extracted from the junction distribution are combined with widely used features to improve the characterization sensitivity by 9.09% over the state of art. The developed method proved effective for the segmentation of the retinal vessels. Higher order tensors along with the implementation of tensor voting via steerable filtering could be employed to further reduce the execution time, and resolve the challenges at vascular junctions. Moreover, the characterization could be advanced to the detection of prolifera- tive retinopathy by extending the supervised learning to include non-proliferative diabetic retinopathy cases or other pathologies. Ultimately, the incorporation of the methods into CAD systems could facilitate screening for the effective reduction of the vision-threatening diabetic retinopathy rates, or the early detection of other than ocular pathologies