Computational models for stuctural analysis of retinal images

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonThe evaluation of retina structures has been of great interest because it could be used as a non-intrusive diagnosis in modern ophthalmology to detect many important eye diseases as well as cardiovascular disorders. A variety of retinal image analysis tools have been developed to assist ophthalmologists and eye diseases experts by reducing the time required in eye screening, optimising the costs as well as providing efficient disease treatment and management systems. A key component in these tools is the segmentation and quantification of retina structures. However, the imaging artefacts such as noise, intensity homogeneity and the overlapping tissue of retina structures can cause significant degradations to the performance of these automated image analysis tools. This thesis aims to provide robust and reliable automated retinal image analysis technique to allow for early detection of various retinal and other diseases. In particular, four innovative segmentation methods have been proposed, including two for retinal vessel network segmentation, two for optic disc segmentation and one for retina nerve fibre layers detection. First, three pre-processing operations are combined in the segmentation method to remove noise and enhance the appearance of the blood vessel in the image, and a Mixture of Gaussians is used to extract the blood vessel tree. Second, a graph cut segmentation approach is introduced, which incorporates the mechanism of vectors flux into the graph formulation to allow for the segmentation of very narrow blood vessels. Third, the optic disc segmentation is performed using two alternative methods: the Markov random field image reconstruction approach detects the optic disc by removing the blood vessels from the optic disc area, and the graph cut with compensation factor method achieves that using prior information of the blood vessels. Fourth, the boundaries of the retinal nerve fibre layer (RNFL) are detected by adapting a graph cut segmentation technique that includes a kernel-induced space and a continuous multiplier based max-flow algorithm. The strong experimental results of our retinal blood vessel segmentation methods including Mixture of Gaussian, Graph Cut achieved an average accuracy of 94:33%, 94:27% respectively. Our optic disc segmentation methods including Markov Random Field and Compensation Factor also achieved an average sensitivity of 92:85% and 85:70% respectively. These results obtained on several public datasets and compared with existing methods have shown that our proposed methods are robust and efficient in the segmenting retinal structures such the blood vessels and the optic disc.Brunel University Londonhttp://bura.brunel.ac.uk/bitstream/2438/10387/1/FulltextThesis.pd

Nonlocal Graph-PDEs and Riemannian Gradient Flows for Image Labeling

In this thesis, we focus on the image labeling problem which is the task of performing unique pixel-wise label decisions to simplify the image while reducing its redundant information. We build upon a recently introduced geometric approach for data labeling by assignment flows [ APSS17 ] that comprises a smooth dynamical system for data processing on weighted graphs. Hereby we pursue two lines of research that give new application and theoretically-oriented insights on the underlying segmentation task. We demonstrate using the example of Optical Coherence Tomography (OCT), which is the mostly used non-invasive acquisition method of large volumetric scans of human retinal tis- sues, how incorporation of constraints on the geometry of statistical manifold results in a novel purely data driven geometric approach for order-constrained segmentation of volumetric data in any metric space. In particular, making diagnostic analysis for human eye diseases requires decisive information in form of exact measurement of retinal layer thicknesses that has be done for each patient separately resulting in an demanding and time consuming task. To ease the clinical diagnosis we will introduce a fully automated segmentation algorithm that comes up with a high segmentation accuracy and a high level of built-in-parallelism. As opposed to many established retinal layer segmentation methods, we use only local information as input without incorporation of additional global shape priors. Instead, we achieve physiological order of reti- nal cell layers and membranes including a new formulation of ordered pair of distributions in an smoothed energy term. This systematically avoids bias pertaining to global shape and is hence suited for the detection of anatomical changes of retinal tissue structure. To access the perfor- mance of our approach we compare two different choices of features on a data set of manually annotated 3 D OCT volumes of healthy human retina and evaluate our method against state of the art in automatic retinal layer segmentation as well as to manually annotated ground truth data using different metrics. We generalize the recent work [ SS21 ] on a variational perspective on assignment flows and introduce a novel nonlocal partial difference equation (G-PDE) for labeling metric data on graphs. The G-PDE is derived as nonlocal reparametrization of the assignment flow approach that was introduced in J. Math. Imaging & Vision 58(2), 2017. Due to this parameterization, solving the G-PDE numerically is shown to be equivalent to computing the Riemannian gradient flow with re- spect to a nonconvex potential. We devise an entropy-regularized difference-of-convex-functions (DC) decomposition of this potential and show that the basic geometric Euler scheme for inte- grating the assignment flow is equivalent to solving the G-PDE by an established DC program- ming scheme. Moreover, the viewpoint of geometric integration reveals a basic way to exploit higher-order information of the vector field that drives the assignment flow, in order to devise a novel accelerated DC programming scheme. A detailed convergence analysis of both numerical schemes is provided and illustrated by numerical experiments

Automatic Segmentation of the Retinal Nerve Fiber Layer by Means of Mathematical Morphology and Deformable Models in 2D Optical Coherence Tomography Imaging

[EN] Glaucoma is a neurodegenerative disease process that leads to progressive damage of the optic nerve to produce visual impairment and blindness. Spectral-domain OCT technology enables peripapillary circular scans of the retina and the measurement of the thickness of the retinal nerve fiber layer (RNFL) for the assessment of the disease status or progression in glaucoma patients. This paper describes a new approach to segment and measure the retinal nerve fiber layer in peripapillary OCT images. The proposed method consists of two stages. In the first one, morphological operators robustly detect the coarse location of the layer boundaries, despite the speckle noise and diverse artifacts in the OCT image. In the second stage, deformable models are initialized with the results of the previous stage to perform a fine segmentation of the boundaries, providing an accurate measurement of the entire RNFL. The results of the RNFL segmentation were qualitatively assessed by ophthalmologists, and the measurements of the thickness of the RNFL were quantitatively compared with those provided by the OCT inbuilt software as well as the state-of-the-art methods.This work was partially funded by Spanish National projects AES2017-PI17/00771 and AES2017-PI17/00821 (Instituto de Salud Carlos III), PID2019-105142RB-C21 (AI4SKIN) (Spanish Ministry of Economy and Competitiveness), PTA2017-14610-I (State Research Spanish Agency), regional project 20901/PI/18 (Fundacion Seneca) and Polytechnic University of Valencia (PAID-01-20).Berenguer-Vidal, R.; Verdú-Monedero, R.; Morales-Sánchez, J.; Sellés-Navarro, I.; Del Amor, R.; García-Pardo, JG.; Naranjo Ornedo, V. (2021). Automatic Segmentation of the Retinal Nerve Fiber Layer by Means of Mathematical Morphology and Deformable Models in 2D Optical Coherence Tomography Imaging. Sensors. 21(23):1-30. https://doi.org/10.3390/s21238027S130212

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

Level set segmentation of retinal structures

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University London.Changes in retinal structure are related to different eye diseases. Various retinal imaging techniques, such as fundus imaging and optical coherence tomography (OCT) imaging modalities, have been developed for non-intrusive ophthalmology diagnoses according to the vasculature changes. However, it is time consuming or even impossible for ophthalmologists to manually label all the retinal structures from fundus images and OCT images. Therefore, computer aided diagnosis system for retinal imaging plays an important role in the assessment of ophthalmologic diseases and cardiovascular disorders. The aim of this PhD thesis is to develop segmentation methods to extract clinically useful information from these retinal images, which are acquired from different imaging modalities. In other words, we built the segmentation methods to extract important structures from both 2D fundus images and 3D OCT images. In the first part of my PhD project, two novel level set based methods were proposed for detecting the blood vessels and optic discs from fundus images. The first one integrates Chan-Vese's energy minimizing active contour method with the edge constraint term and Gaussian Mixture Model based term for blood vessels segmentation, while the second method combines the edge constraint term, the distance regularisation term and the shape-prior term for locating the optic disc. Both methods include the pre-processing stage, used for removing noise and enhancing the contrast between the object and the background. Three automated layer segmentation methods were built for segmenting intra-retinal layers from 3D OCT macular and optic nerve head images in the second part of my PhD project. The first two methods combine different methods according to the data characteristics. First, eight boundaries of the intra-retinal layers were detected from the 3D OCT macular images and the thickness maps of the seven layers were produced. Second, four boundaries of the intra-retinal layers were located from 3D optic nerve head images and the thickness maps of the Retinal Nerve Fiber Layer (RNFL) were plotted. Finally, the choroidal layer segmentation method based on the Level Set framework was designed, which embedded with the distance regularisation term, edge constraint term and Markov Random Field modelled region term. The thickness map of the choroidal layer was calculated and shown.Department of Computer Science, Brunel University London

Retinal Fundus Image Analysis for Diagnosis of Glaucoma: A Comprehensive Survey

© 2016 IEEE. The rapid development of digital imaging and computer vision has increased the potential of using the image processing technologies in ophthalmology. Image processing systems are used in standard clinical practices with the development of medical diagnostic systems. The retinal images provide vital information about the health of the sensory part of the visual system. Retinal diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, Stargardt's disease, and retinopathy of prematurity, can lead to blindness manifest as artifacts in the retinal image. An automated system can be used for offering standardized large-scale screening at a lower cost, which may reduce human errors, provide services to remote areas, as well as free from observer bias and fatigue. Treatment for retinal diseases is available; the challenge lies in finding a cost-effective approach with high sensitivity and specificity that can be applied to large populations in a timely manner to identify those who are at risk at the early stages of the disease. The progress of the glaucoma disease is very often quiet in the early stages. The number of people affected has been increasing and patients are seldom aware of the disease, which can cause delay in the treatment. A review of how computer-aided approaches may be applied in the diagnosis and staging of glaucoma is discussed here. The current status of the computer technology is reviewed, covering localization and segmentation of the optic nerve head, pixel level glaucomatic changes, diagonosis using 3-D data sets, and artificial neural networks for detecting the progression of the glaucoma disease

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

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

Optical designs and image processing algorithms for optical coherence tomography detection of glaucoma

textOptical Coherence Tomography (OCT) is an optical tomography technique which provides high resolution non-invasive three-dimensional (3D) structural images of the sample based on coherent properties of light. The dissertation focuses on the use of OCT systems for detecting glaucoma, which is the second leading cause of blindness worldwide. First, as a prerequisite of analyzing ophthalmologic OCT images, a retinal sublayer segmentation algorithm is presented and implemented with GPU assisted computation. Then, a polarization-sensitive optical coherence tomography (PS-OCT) system was constructed for the study of glaucoma. Three closely related clinical and animal studies on early-stage glaucoma detection using either OCT or PS-OCT were performed. Statistical analysis of the study results indicates that the scattering property of retinal nerve fiber layer (RNFL) is the earliest indicator for glaucoma. Finally, to investigate the scattering properties of RNFL, a pathlength-multiplexed scattering-angle-diverse optical coherence tomography (PM-SAD-OCT) system was designed and built. PM-SAD-OCT images were collected from human and rodent retina as well as earthworm nerve cord. PM-SAD-OCT system shows promising potentials to detect neurodegenerative diseases including glaucoma.Biomedical Engineerin