Automatic detection of drusen associated with age-related macular degeneration in optical coherence tomography: a graph-based approach

Tese de Doutoramento em Líderes para Indústrias TecnológicasThe age-related macular degeneration (AMD) starts to manifest itself with the appearance of drusen. Progressively, the drusen increase in size and in number without causing alterations to vision. Nonetheless, their quantification is important because it correlates with the evolution of the disease to an advanced stage, which could lead to the loss of central vision. Manual quantification of drusen is impractical, since it is time-consuming and it requires specialized knowledge. Therefore, this work proposes a method for quantifying drusen automatically In this work, it is proposed a method for segmenting boundaries limiting drusen and another method for locating them through classification. The segmentation method is based on a multiple surface framework that is adapted for segmenting the limiting boundaries of drusen: the inner boundary of the retinal pigment epithelium + drusen complex (IRPEDC) and the Bruch’s membrane (BM). Several segmentation methods have been considerably successful in segmenting layers of healthy retinas in optical coherence tomography (OCT) images. These methods were successful because they incorporate prior information and regularization. However, these factors have the side-effect of hindering the segmentation in regions of altered morphology that often occur in diseased retinas. The proposed segmentation method takes into account the presence of lesion related with AMD, i.e., drusen and geographic atrophies (GAs). For that, it is proposed a segmentation scheme that excludes prior information and regularization that is only valid for healthy regions. Even with this segmentation scheme, the prior information and regularization can still cause the oversmoothing of some drusen. To address this problem, it is also proposed the integration of local shape priors in the form of a sparse high order potentials (SHOPs) into the multiple surface framework. Drusen are commonly detected by thresholding the distance among the boundaries that limit drusen. This approach misses drusen or portions of drusen with a height below the threshold. To improve the detection of drusen, Dufour et al. [1] proposed a classification method that detects drusen using textural information. In this work, the method of Dufour et al. [1] is extended by adding new features and performing multi-label classification, which allow the individual detection of drusen when these occur in clusters. Furthermore, local information is incorporated into the classification by combining the classifier with a hidden Markov model (HMM). Both the segmentation and detections methods were evaluated in a database of patients with intermediate AMD. The results suggest that both methods frequently perform better than some methods present in the literature. Furthermore, the results of these two methods form drusen delimitations that are closer to expert delimitations than two methods of the literature.A degenerescência macular relacionada com a idade (DMRI) começa a manifestar-se com o aparecimento de drusas. Progressivamente, as drusas aumentam em tamanho e em número sem causar alterações à visão. Porém, a sua quantificação é importante porque está correlacionada com a evolução da doença para um estado avançado, levar à perda de visão central. A quantificação manual de drusas é impraticável, já que é demorada e requer conhecimento especializado. Por isso, neste trabalho é proposto um método para segmentar drusas automaticamente. Neste trabalho, é proposto um método para segmentar as fronteiras que limitam as drusas e outro método para as localizar através de classificação. O método de segmentação é baseado numa ”framework” de múltiplas superfícies que é adaptada para segmentar as fronteiras que limitam as drusas: a fronteira interior do epitélio pigmentar + complexo de drusas e a membrana de Bruch. Vários métodos de segmentação foram consideravelmente bem-sucedidos a segmentar camadas de retinas saudáveis em imagens de tomografia de coerência ótica. Estes métodos foram bem-sucedidos porque incorporaram informação prévia e regularização. Contudo, estes fatores têm como efeito secundário dificultar a segmentação em regiões onde a morfologia da retina está alterada devido a doenças. O método de segmentação proposto toma em consideração a presença de lesões relacionadas com DMRI, .i.e., drusas e atrofia geográficas. Para isso, é proposto um esquema de segmentação que exclui informação prévia e regularização que são válidas apenas em regiões saudáveis da retina. Mesmo com este esquema de segmentação, a informação prévia e a regularização podem causar a suavização excessiva de algumas drusas. Para tentar resolver este problema, também é proposta a integração de informação prévia local sob a forma de potenciais esparsos de ordem elevada na ”framework” multi-superfície. As drusas são usalmente detetadas por ”thresholding” da distância entre as fronteiras que limitam as drusas. Esta abordagem falha drusas ou porções de drusas abaixo do ”threshold”. Para melhorar a deteção de drusas, Dufour et al. [1] propuseram um método de classificação que deteta drusas usando informação de texturas. Neste trabalho, o método de Dufour et al. [1] é estendido, adicionando novas características e realizando uma classificação com múltiplas classes, o que permite a deteção individual de drusas em aglomerados. Além disso, é incorporada informação local na classificação, combinando o classificador com um modelo oculto de Markov. Ambos os métodos de segmentação e deteção foram avaliados numa base de dados de pacientes com DMRI intermédia. Os resultados sugerem que ambos os métodos obtêm frequentemente melhores resultados que alguns métodos descritos na literatura. Para além disso, os resultados destes dois métodos formam delimitações de drusas que estão mais próximas das delimitações dos especialistas que dois métodos da literatura.This work was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941. Furthermore, the Portuguese funding institution Fundação Calouste Gulbenkian has conceded me a Ph.D. grant for this work. For that, I wish to acknowledge this institution. Additionally, I want to thank one of its members, Teresa Burnay, for all her assistance with issues related with the grant, for believing that my work was worth supporting and for encouraging me to apply for the grant

Active contour method for ILM segmentation in ONH volume scans in retinal OCT

The optic nerve head (ONH) is affected by many neurodegenerative and autoimmune inflammatory conditions. Optical coherence tomography can acquire high-resolution 3D ONH scans. However, the ONH's complex anatomy and pathology make image segmentation challenging. This paper proposes a robust approach to segment the inner limiting membrane (ILM) in ONH volume scans based on an active contour method of Chan-Vese type, which can work in challenging topological structures. A local intensity fitting energy is added in order to handle very inhomogeneous image intensities. A suitable boundary potential is introduced to avoid structures belonging to outer retinal layers being detected as part of the segmentation. The average intensities in the inner and outer region are then resealed locally to account for different brightness values occurring among the ONH center. The appropriate values for the parameters used in the complex computational model are found using an optimization based on the differential evolution algorithm. The evaluation of results showed that the proposed framework significantly improved segmentation results compared to the commercial solution

Recent Developments in Detection of Central Serous Retinopathy through Imaging and Artificial Intelligence Techniques – A Review

Central Serous Retinopathy (CSR) or Central Serous Chorioretinopathy (CSC) is a significant disease that causes blindness and vision loss among millions of people worldwide. It transpires as a result of accumulation of watery fluids behind the retina. Therefore, detection of CSR at early stages allows preventive measures to avert any impairment to the human eye. Traditionally, several manual methods for detecting CSR have been developed in the past; however, they have shown to be imprecise and unreliable. Consequently, Artificial Intelligence (AI) services in the medical field, including automated CSR detection, are now possible to detect and cure this disease. This review assessed a variety of innovative technologies and researches that contribute to the automatic detection of CSR. In this review, various CSR disease detection techniques, broadly classified into two categories: a) CSR detection based on classical imaging technologies, and b) CSR detection based on Machine/Deep Learning methods, have been reviewed after an elaborated evaluation of 29 different relevant articles. Additionally, it also goes over the advantages, drawbacks and limitations of a variety of traditional imaging techniques, such as Optical Coherence Tomography Angiography (OCTA), Fundus Imaging and more recent approaches that utilize Artificial Intelligence techniques. Finally, it is concluded that the most recent Deep Learning (DL) classifiers deliver accurate, fast, and reliable CSR detection. However, more research needs to be conducted on publicly available datasets to improve computation complexity for the reliable detection and diagnosis of CSR disease

Neue Methoden der Nachbearbeitung und Analyse retinaler optischer Kohärenztomografieaufnahmen bei neurologischen Erkrankungen

Viele neurologische Krankheiten verursachen Veränderungen in der Netzhaut, die mit Hilfe der optischen Kohärenztomography (optical coherence tomography, OCT) dargestellt werden können. Dabei entstehen viele Bilddaten, deren Auswertung zeitintensiv ist und geschultes Personal erfordert. Ziel dieser Arbeit war die Entwicklung neuer Methoden zur Vorverarbeitung und Analyse retinaler OCT-Bilddaten, um Outcome-Parameter für Studien und diagnostische Marker für neurologische Erkrankungen zu verbessern. Dazu wurden Methoden für zwei wichtige Aufnahmebereiche der Netzhaut, den Sehnervenkopf (optic nerve head, ONH) und die Makula, entwickelt. Für den ONH-Bereich wurde eine automatische Segmentierung auf Basis aktiver Konturen entwickelt, die eine akkurate Segmentierung der inneren Grenzmembran auch bei komplexer Topografie ermöglicht. Für den Bereich um die Makula entstand eine intraretinale Schichtensegmentierungspipeline, die von der Auswahl der Bilddaten über die automatische Segmentierung sowie die manuelle Nachkorrektur bis zur Ausgabe verschiedener Schichtdicken in Tabellenform reicht. Für beide Aufnahmebereiche wurden mehrere Programme entwickelt, die auf einer gemeinsamen Basis zur Verarbeitung von OCT-Daten fußen. Eines dieser Programme bietet eine grafische Oberfläche zur manuellen Verarbeitung der Bilddaten. Mit dieser Software wurden Teile der Referenzdaten manuell erstellt, die innere Grenzmembran des ONH automatisch segmentiert sowie eine komfortable Nachbearbeitung von intraretinalen Segmentierungen vorgenommen. Dies ermöglichte die automatische Auswertung morphologischer Parameter des ONH, wovon einige signifikante Unterschiede zwischen Patienten mit neurologischen Krankheiten und gesunden Kontrollen zeigten. Weiter kam die Schichtensegmentierungspipeline beim Aufbau einer normativen Datenbank sowie in einer Studie zum Zusammenhang des retinalen Schadens mit der kritischen Flimmerfrequenz zum Einsatz. Ein Teil der Software wurde als freie und quelloffene Software (free and open-source software, FOSS) und der normative Datensatz für die Verwendung in anderen Studien freigegeben. Beides wird bereits in weiteren Studien eingesetzt und wird auch die Durchführung zukünftiger Studien vereinfachen sowie die Entwicklung neuer Methoden unterstützen.Many neurological diseases cause changes in the retina, which can be visualized using optical coherence tomography (OCT). This process produces large amounts of image data. Its evaluation is time-consuming and requires medically trained personnel. This dissertation aims to develop new methods for preprocessing and analyzing retinal OCT data in order to improve outcome parameters for clinical studies and diagnostic markers for neurological diseases. For this purpose, methods concerning the regions of two landmarks of the retina, the optic nerve head (ONH) and the macula, were developed. For the ONH, an automatic segmentation method based on active contours was developed, which allows accurate segmentation of the inner limiting membrane even in complex topography. For the macular region, an intraretinal layer segmentation pipeline from image data via automatic segmentation to manual post-correction and the output of different layer thicknesses in tabular form was developed. For both, ONH and macular region, several programs were developed, which share a common basis for processing OCT data. One of these programs offers a graphical user interface for the manual processing of image data. Parts of the reference data were created manually using this software. Moreover, the inner limiting membrane of the ONH was segmented automatically and post-processing of intraretinal segmentations was performed. This allowed for automatic evaluation of morphological parameters of the ONH, some of which showed significant differences between patients with neurological diseases and the healthy control group. Furthermore, the layer segmentation pipeline was utilized to create a normative database as well as to investigate the correlation of retinal damage and critical flicker frequency. Part of the software was released as free and open-source software (FOSS) and the normative data set was released for use in other studies. Both are already being used in further studies and will also aid in future studies, as well as support the development of new methods

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

Image classification : a study in age-related macular degeneration screening

This thesis presents research work conducted in the field of image mining. More specifically, the work is directed at the employment of image classification techniques to classify images where features of interest are very difficult to distinguish. In this context, three distinct approaches to image classification are proposed. The first is founded on a time series based image representation, whereby each image is defined in terms of histograms that in turn are presented as "time series" curves. A Case Based Reasoning (CBR) mechanism, coupled with a Time Series Analysis (TSA) technique, is then applied to classify new "unseen" images. The second proposed approach uses statistical parameters that are extracted from the images either directly or indirectly. These parameters are then represented in a tabular form from which a classifier can be built on. The third is founded on a tree based representation, whereby a hierarchical decomposition technique is proposed. The images are successively decomposed into smaller segments until each segment describes a uniform set of features. The resulting tree structures allow for the application of weighted frequent sub-graph mining to identify feature vectors representing each image. A standard classifier generator is then applied to this feature vector representation to produce the desired classifier. The presented evaluation, applied to all three approaches, is directed at the classification of retinal colour fundus images; the aim is to screen for an eye condition known as Age-related Macular Degeneration (AMD). Of all the approaches considered in this thesis, the tree based representation coupled with weighted frequent sub-graph mining produced the best performance. The evaluation also indicated that a sound foundation has been established for future potential AMD screening programmes