Vessel identification in diabetic retinopathy

Diabetic retinopathy is the single largest cause of sight loss and blindness in 18 to 65 year olds. Screening programs for the estimated one to six per- cent of the diabetic population have been demonstrated to be cost and sight saving, howeverthere are insufficient screening resources. Automatic screen-ing systems may help solve this resource short fall. This thesis reports on research into an aspect of automatic grading of diabetic retinopathy; namely the identification of the retinal blood vessels in fundus photographs. It de-velops two vessels segmentation strategies and assess their accuracies. A literature review of retinal vascular segmentation found few results, and indicated a need for further development. The two methods for vessel segmentation were investigated in this thesis are based on mathematical morphology and neural networks. Both methodologies are verified on independently labeled data from two institutions and results are presented that characterisethe trade off betweenthe ability to identify vesseland non-vessels data. These results are based on thirty five images with their retinal vessels labeled. Of these images over half had significant pathology and or image acquisition artifacts. The morphological segmentation used ten images from one dataset for development. The remaining images of this dataset and the entire set of 20 images from the seconddataset were then used to prospectively verify generaliastion. For the neural approach, the imageswere pooled and 26 randomly chosenimageswere usedin training whilst 9 were reserved for prospective validation. Assuming equal importance, or cost, for vessel and non-vessel classifications, the following results were obtained; using mathematical morphology 84% correct classification of vascular and non-vascular pixels was obtained in the first dataset. This increased to 89% correct for the second dataset. Using the pooled data the neural approach achieved 88% correct identification accuracy. The spread of accuracies observed varied. It was highest in the small initial dataset with 16 and 10 percent standard deviation in vascular and non-vascular cases respectively. The lowest variability was observed in the neural classification, with a standard deviation of 5% for both accuracies. The less tangible outcomes of the research raises the issueof the selection and subsequent distribution of the patterns for neural network training. Unfortunately this indication would require further labeling of precisely those cases that were felt to be the most difficult. I.e. the small vessels and border conditions between pathology and the retina. The more concrete, evidence based conclusions,characterise both the neural and the morphological methods over a range of operating points. Many of these operating points are comparable to the few results presented in the literature. The advantage of the author's approach lies in the neural method's consistent as well as accurate vascular classification

Vessel identification in diabetic retinopathy

Diabetic retinopathy is the single largest cause of sight loss and blindness in 18 to 65 year olds. Screening programs for the estimated one to six per- cent of the diabetic population have been demonstrated to be cost and sight saving, howeverthere are insufficient screening resources. Automatic screen-ing systems may help solve this resource short fall. This thesis reports on research into an aspect of automatic grading of diabetic retinopathy; namely the identification of the retinal blood vessels in fundus photographs. It de-velops two vessels segmentation strategies and assess their accuracies. A literature review of retinal vascular segmentation found few results, and indicated a need for further development. The two methods for vessel segmentation were investigated in this thesis are based on mathematical morphology and neural networks. Both methodologies are verified on independently labeled data from two institutions and results are presented that characterisethe trade off betweenthe ability to identify vesseland non-vessels data. These results are based on thirty five images with their retinal vessels labeled. Of these images over half had significant pathology and or image acquisition artifacts. The morphological segmentation used ten images from one dataset for development. The remaining images of this dataset and the entire set of 20 images from the seconddataset were then used to prospectively verify generaliastion. For the neural approach, the imageswere pooled and 26 randomly chosenimageswere usedin training whilst 9 were reserved for prospective validation. Assuming equal importance, or cost, for vessel and non-vessel classifications, the following results were obtained; using mathematical morphology 84% correct classification of vascular and non-vascular pixels was obtained in the first dataset. This increased to 89% correct for the second dataset. Using the pooled data the neural approach achieved 88% correct identification accuracy. The spread of accuracies observed varied. It was highest in the small initial dataset with 16 and 10 percent standard deviation in vascular and non-vascular cases respectively. The lowest variability was observed in the neural classification, with a standard deviation of 5% for both accuracies. The less tangible outcomes of the research raises the issueof the selection and subsequent distribution of the patterns for neural network training. Unfortunately this indication would require further labeling of precisely those cases that were felt to be the most difficult. I.e. the small vessels and border conditions between pathology and the retina. The more concrete, evidence based conclusions,characterise both the neural and the morphological methods over a range of operating points. Many of these operating points are comparable to the few results presented in the literature. The advantage of the author's approach lies in the neural method's consistent as well as accurate vascular classification.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Novel Insight into Morphological Features and Vascular Profile of Selected Macular Dystrophies Using Swept-Source Optical Coherence Tomography and Optical Coherence Tomography Angiography

Our perception of macular dystrophies has evolved overtime from collective grouping into hereditary disorders of unclear etiology and no effective treatment to avid search for the underlying pathogenic mechanism that would provide base for future therapy. A causal conjunction between abnormalities in the photoreceptors layer and the RPE—Bruch’s membrane complex and abnormal profile of the retinal vascular plexuses and the choriocapillaris—stands out as a plausible theory of pathogenesis. The recently introduced swept-source optical coherence tomography (SS-OCT) technology incorporates long-wavelength (1050-nm) scanning light, less susceptibility to sensitivity roll-off, and ultrahigh-speed image acquisition. These features enabled in vivo noninvasive visualization of different strata of the outer retina and the choriocapillaris with unprecedented finesse. Furthermore, the SS-OCT technology incorporated a blood flow detection algorithm; OCTARA that in tandem with the deeper penetration and superior axial resolution of SS-OCT enabled detailed assessment of the retinal capillary plexuses and the choriocapillaris in terms of structure and density. This novel technology could help explore yet undiscovered frontiers in the pathophysiology of macular dystrophies and guide future therapeutic approaches. This chapter includes a review of literature along with the authors’ experience in imaging selected macular dystrophies using SS-OCT and SS-OCT angiography (SS-OCTA)

Retinal Vascular Network Topology Reconstruction and Artery/Vein Classification via Dominant Set Clustering

The estimation of vascular network topology in complex networks is important in understanding the relationship between vascular changes and a wide spectrum of diseases. Automatic classification of the retinal vascular trees into arteries and veins is of direct assistance to the ophthalmologist in terms of diagnosis and treatment of eye disease. However, it is challenging due to their projective ambiguity and subtle changes in appearance, contrast and geometry in the imaging process. In this paper, we propose a novel method that is capable of making the artery/vein (A/V) distinction in retinal color fundus images based on vascular network topological properties. To this end, we adapt the concept of dominant set clustering and formalize the retinal blood vessel topology estimation and the A/V classification as a pairwise clustering problem. The graph is constructed through image segmentation, skeletonization and identification of significant nodes. The edge weight is defined as the inverse Euclidean distance between its two end points in the feature space of intensity, orientation, curvature, diameter, and entropy. The reconstructed vascular network is classified into arteries and veins based on their intensity and morphology. The proposed approach has been applied to five public databases, INSPIRE, IOSTAR, VICAVR, DRIVE and WIDE, and achieved high accuracies of 95.1%, 94.2%, 93.8%, 91.1%, and 91.0%, respectively. Furthermore, we have made manual annotations of the blood vessel topologies for INSPIRE, IOSTAR, VICAVR, and DRIVE datasets, and these annotations are released for public access so as to facilitate researchers in the community

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

Mathematical Morphology for Quantification in Biological & Medical Image Analysis

Mathematical morphology is an established field of image processing first introduced as an application of set and lattice theories. Originally used to characterise particle distributions, mathematical morphology has gone on to be a core tool required for such important analysis methods as skeletonisation and the watershed transform. In this thesis, I introduce a selection of new image analysis techniques based on mathematical morphology. Utilising assumptions of shape, I propose a new approach for the enhancement of vessel-like objects in images: the bowler-hat transform. Built upon morphological operations, this approach is successful at challenges such as junctions and robust against noise. The bowler-hat transform is shown to give better results than competitor methods on challenging data such as retinal/fundus imagery. Building further on morphological operations, I introduce two novel methods for particle and blob detection. The first of which is developed in the context of colocalisation, a standard biological assay, and the second, which is based on Hilbert-Edge Detection And Ranging (HEDAR), with regard to nuclei detection and counting in fluorescent microscopy. These methods are shown to produce accurate and informative results for sub-pixel and supra-pixel object counting in complex and noisy biological scenarios. I propose a new approach for the automated extraction and measurement of object thickness for intricate and complicated vessels, such as brain vascular in medical images. This pipeline depends on two key technologies: semi-automated segmentation by advanced level-set methods and automatic thickness calculation based on morphological operations. This approach is validated and results demonstrating the broad range of challenges posed by these images and the possible limitations of this pipeline are shown. This thesis represents a significant contribution to the field of image processing using mathematical morphology and the methods within are transferable to a range of complex challenges present across biomedical image analysis

Visual Impairment and Blindness

Blindness and vision impairment affect at least 2.2 billion people worldwide with most individuals having a preventable vision impairment. The majority of people with vision impairment are older than 50 years, however, vision loss can affect people of all ages. Reduced eyesight can have major and long-lasting effects on all aspects of life, including daily personal activities, interacting with the community, school and work opportunities, and the ability to access public services. This book provides an overview of the effects of blindness and visual impairment in the context of the most common causes of blindness in older adults as well as children, including retinal disorders, cataracts, glaucoma, and macular or corneal degeneration

Eye as a window to the brain: investigating the clinical utility of retinal imaging derived biomarkers in the phenotyping of neurodegenerative disease.

Background Neurodegenerative diseases, like multiple sclerosis, dementia and motor neurone disease, represent one of the major public health threats of our time. There is a clear persistent need for novel, affordable, and patient‐acceptable biomarkers of these diseases, to assist with diagnosis, prognosis and impact of interventions. And these biomarkers need to be sensitive, specific and precise. The retina is an attractive site for exploring this potential, as it is easily accessible to non‐invasive imaging. Remarkable technology revolutions in retinal imaging are enabling us to see the retina in microscopic level detail, and measure neuronal and vascular integrity. Aims and objectives I therefore propose that retinal imaging could provide reliable and accurate markers of these neurological diseases. In this project, I aimed to explore the clinical utility of retinal imaging derived measures of retinal neuronal and vessel size and morphology, and determine their candidacy for being reliable biomarkers in these diseases. I also aimed to detail the methods of retinal imaging acquisition, and processing, and the principles underlying all these stages, in relation to understanding of retinal structure and function. This provides an essential foundation to the application of retinal imaging analysis, highlighting both the strengths and potential weaknesses of retinal biomarkers and how they are interpreted. Methods After performing detailed systematic reviews and meta‐analyses of the existing work on retinal biomarkers of neurodegenerative disease, I carried out a prospective, controlled, cross‐sectional study of retinal image analysis, in patients with MS, dementia, and ALS. This involved developing new software for vessel analysis, to add value and maximise the data available from patient imaging episodes. Results From the systematic reviews, I identified key unanswered questions relating to the detailed analysis and utility of neuroretinal markers, and diseases with no studies yet performed of retinal biomarkers, such as non‐AD dementias. I recruited and imaged 961 participants over a two‐year period, and found clear patterns of significance in the phenotyping of MS, dementia and ALS. Detailed analysis has provided new insights into how the retina may yield important disease information for the individual patient, and also generate new hypotheses with relation to the disease pathophysiology itself. Conclusions Overall, the results show that retinal imaging derived biomarkers have an important and specific role in the phenotyping of neurodegenerative diseases, and support the hypothesis that the eye is an important window to neurological brain disease