A Polar Map Based Approach Using Retinal Fundus Images for Glaucoma Detection

Cup-to-disc ratio is commonly used as an important parameter for glaucoma screening, involving segmentation of the optic cup on fundus images. We propose a novel polar map representation of the optic disc, using a combination of supervised and unsupervised cup segmentation techniques, for detection of glaucoma. Instead of performing hard thresholding on the segmentation output to extract the cup, we consider the cup confidence scores inside the disc to construct a polar map, and extract sector-wise features for learning a glaucoma risk probability (GRP) for the image. We compare the performance of GRP vis-à-vis the cup-to-disc ratio (CDR). On an evaluation dataset of 100 images from the publicly available RIM-ONE database, our method achieves 82% sensitivity at 84% specificity, and 96% sensitivity at 60% specificity (AUC of 0.8964). Experiments indicate that the polar map based method can provide a more discriminatory glaucoma risk probability score compared to CDR

Towards Complete Ocular Disease Diagnosis in Color Fundus Image

Non-invasive assessment of retinal fundus image is well suited for early detection of ocular disease and is facilitated more by advancements in computed vision and machine learning. Most of the Deep learning based diagnosis system gives just a diagnosis(absence or presence) of a certain number of diseases without hinting the underlying pathological abnormalities. We attempt to extract such pathological markers, as an ophthalmologist would do, in this thesis and pave a way for explainable diagnosis/assistance task. Such abnormalities can be present in various regions of a fundus image including vasculature, Optic Nerve Disc/Cup, or even in non-vascular region. This thesis consist of series of novel techniques starting from robust retinal vessel segmentation, complete vascular topology extraction, and better ArteryVein classification. Finally, we compute two of the most important vascular anomalies-arteryvein ratio and vessel tortuosity. While most of the research focuses on vessel segmentation, and artery-vein classification, we have successfully advanced this line of research one step further. We believe it can be a very valuable framework for future researcher working on automated retinal disease diagnosis

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

Effunet-spagen: An efficient and spatial generative approach to glaucoma detection

Current research in automated disease detection focuses on making algorithms “slimmer” reducing the need for large training datasets and accelerating recalibration for new data while achieving high accuracy. The development of slimmer models has become a hot research topic in medical imaging. In this work, we develop a two-phase model for glaucoma detection, identifying and exploiting a redundancy in fundus image data relating particularly to the geometry. We propose a novel algorithm for the cup and disc segmentation “EffUnet” with an efficient convolution block and combine this with an extended spatial generative approach for geometry modelling and classification, termed “SpaGen” We demonstrate the high accuracy achievable by EffUnet in detecting the optic disc and cup boundaries and show how our algorithm can be quickly trained with new data by recalibrating the EffUnet layer only. Our resulting glaucoma detection algorithm, “EffUnet-SpaGen”, is optimized to significantly reduce the computational burden while at the same time surpassing the current state-of-art in glaucoma detection algorithms with AUROC 0.997 and 0.969 in the benchmark online datasets ORIGA and DRISHTI, respectively. Our algorithm also allows deformed areas of the optic rim to be displayed and investigated, providing explainability, which is crucial to successful adoption and implementation in clinical settings

Spatial and spatio-temporal statistical analyses of retinal images: a review of methods and applications.

Background: Clinical research and management of retinal diseases greatly depend on the interpretation of retinal images and often longitudinally collected images. Retinal images provide context for spatial data, namely the location of specific pathologies within the retina. Longitudinally collected images can show how clinical events at one point can affect the retina over time. In this review, we aimed to assess statistical approaches to spatial and spatio-temporal data in retinal images. We also review the spatio-temporal modelling approaches used in other medical image types. Methods: We conducted a comprehensive literature review of both spatial or spatio-temporal approaches and non-spatial approaches to the statistical analysis of retinal images. The key methodological and clinical characteristics of published papers were extracted. We also investigated whether clinical variables and spatial correlation were accounted for in the analysis. Results: Thirty-four papers that included retinal imaging data were identified for full-text information extraction. Only 11 (32.4%) papers used spatial or spatio-temporal statistical methods to analyse images, others (23 papers, 67.6%) used non-spatial methods. Twenty-eight (82.4%) papers reported images collected cross-sectionally, while 6 (17.6%) papers reported analyses on images collected longitudinally. In imaging areas outside of ophthalmology, 19 papers were identified with spatio-temporal analysis, and multiple statistical methods were recorded. Conclusions: In future statistical analyses of retinal images, it will be beneficial to clearly define and report the spatial distributions studied, report the spatial correlations, combine imaging data with clinical variables into analysis if available, and clearly state the software or packages used

Knowledge Mining In The Clinical Assessment Of Glaucoma

Glaucoma is a leading cause of irreversible blindness and visual impairment. In the clinic, glaucomatous damage can be characterized by structural changes in the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) that can be evaluated by various retinal-imaging techniques such as scanning laser polarimetry and optical coherence tomography (OCT). The structural damage can lead to functional damage in the visual field (VF), normally assessed with standard automated perimetry, which assesses the differential light sensitivity in the field of view. The clinical measurements of retinal structure and visual function play an important role in the detection and management of glaucoma, but the data generated is often complex and highly variable, thus making it hard to clinically interpret. The purpose of this thesis was to investigate knowledge mining procedures for extracting clinically useful information from these measurements. Knowledge mining describes iterative divide-and-conquer type analyses of large-scale questions: solutions to individual smaller problems are used to generate better quality knowledge, which in the case of work reported in this thesis can be translated into clinically useful analysis tools. This thesis describes five knowledge mining procedures specifically developed and applied to structural and functional measurements in glaucoma: (1) probabilistic inference to aid image acquisition of OCT images; (2) a robust and efficient segmentation algorithm to extract features of retina tissue layer structures in large-scale 3-dimensional image volumes acquired by OCT; (3) a predictive structure-function relationship model to bridge the retinal structure and visual function measurements in glaucoma; (4) quantification and visualization of structure-function discordance using the model about structure-function relationship; (5) integration of structural and functional measurements to improve the reproducibility of the measurements. In conclusion the knowledge mining approaches improved the acquisition and/or accuracy of the measurements and provide new clinical analysis tools to detect and manage glaucoma

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

An active contour approach for segmentation of intra-retinal layers in optical coherence tomography images

Optical Coherence Tomography (OCT) is a non-invasive, depth-resolved imaging modality that has become a prominent ophthalmic diagnostic technique. We present a novel segmentation algorithm based on Chan-Vese\u27s energy-minimizing active contours to detect intra-retinal layers in OCT images. A multi-phase framework with a circular shape prior is adopted to model the boundaries of retinal layers and estimate shape parameters using least squares. We use a contextual scheme to balance the weight of different terms in the energy functional. The results from various synthetic experiments and segmentation results on rat OCT images are presented, demonstrating the strength of our method to detect the desired layers with sufficient accuracy even in the presence of intensity inhomogeneity. Our algorithm achieved an average Dice similarity coefficient of 0.84 over all segmented layers, and of 0.94 for the combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, which are critical layers for glaucomatous degeneration