End-to-End Fovea Localisation in Colour Fundus Images with a Hierarchical Deep Regression Network

Accurately locating the fovea is a prerequisite for developing computer aided diagnosis (CAD) of retinal diseases. In colour fundus images of the retina, the fovea is a fuzzy region lacking prominent visual features and this makes it difficult to directly locate the fovea. While traditional methods rely on explicitly extracting image features from the surrounding structures such as the optic disc and various vessels to infer the position of the fovea, deep learning based regression technique can implicitly model the relation between the fovea and other nearby anatomical structures to determine the location of the fovea in an end-to-end fashion. Although promising, using deep learning for fovea localisation also has many unsolved challenges. In this paper, we present a new end-to-end fovea localisation method based on a hierarchical coarse-to-fine deep regression neural network. The innovative features of the new method include a multi-scale feature fusion technique and a self-attention technique to exploit location, semantic, and contextual information in an integrated framework, a multi-field-of-view (multi-FOV) feature fusion technique for context-aware feature learning and a Gaussian-shiftcropping method for augmenting effective training data. We present extensive experimental results on two public databases and show that our new method achieved state of- the-art performances. We also present a comprehensive ablation study and analysis to demonstrate the technical soundness and effectiveness of the overall framework and its various constituent components

REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs

[EN] Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MIC-CAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.This work was supported by the Christian Doppler Research Association, the Austrian Federal Ministry for Digital and Economic Affairs and the National Foundation for Research, Technology and Development, J.I.O is supported by WWTF (Medical University of Vienna: AugUniWien/FA7464A0249, University of Vienna: VRG12- 009). Team Masker is supported by Natural Science Foundation of Guangdong Province of China (Grant 2017A030310647). Team BUCT is partially supported by the National Natural Science Foundation of China (Grant 11571031). The authors would also like to thank REFUGE study group for collaborating with this challenge.Orlando, JI.; Fu, H.; Breda, JB.; Van Keer, K.; Bathula, DR.; Diaz-Pinto, A.; Fang, R.... (2020). 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Impact of eye fundus image preprocessing on key objects segmentation for glaucoma identification

The pathological changes in the eye fundus image, especially around Optic Disc (OD) and Optic Cup (OC) may indicate eye diseases such as glaucoma. Therefore, accurate OD and OC segmentation is essential. The variety in images caused by different eye fundus cameras makes the complexity for the existing deep learning (DL) networks in OD and OC segmentation. In most research cases, experiments were conducted on individual data sets only and the results were obtained for that specific data sample. Our future goal is to develop a DL method that segments OD and OC in any kind of eye fundus image but the application of the mixed training data strategy is in the initiation stage and the image preprocessing is not discussed. Therefore, the aim of this paper is to evaluate the mage preprocessing impact on OD and OC segmentation in different eye fundus images aligned by size. We adopted a mixed training data strategy by combining images of DRISHTI-GS, REFUGE, and RIM-ONE datasets, and applied image resizing incorporating various interpolation methods, namely bilinear, nearest neighbor, and bicubic for image resolution alignment. The impact of image preprocessing on OD and OC segmentation was evaluated using three convolutional neural networks Attention U-Net, Residual Attention U-Net (RAUNET), and U-Net++. The experimental results show that the most accurate segmentation is achieved by resizing images to a size of 512 x 512 px and applying bicubic interpolation. The highest Dice of 0.979 for OD and 0.877 for OC are achieved on  RISHTI-GS test dataset, 0.973 for OD and 0.874 for OC on the REFUGE test dataset, 0.977 for OD and 0:855 for OC on RIM-ONE test dataset. Anova and Levene’s tests with statistically significant evidence at α = 0.05 show that the chosen size in image resizing has impact on the OD and OC segmentation results, meanwhile, the interpolation method does influent OC segmentation only

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

Novel Fundus Image Preprocessing for Retcam Images to Improve Deep Learning Classification of Retinopathy of Prematurity

Retinopathy of Prematurity (ROP) is a potentially blinding eye disorder because of damage to the eye's retina which can affect babies born prematurely. Screening of ROP is essential for early detection and treatment. This is a laborious and manual process which requires trained physician performing dilated ophthalmological examination which can be subjective resulting in lower diagnosis success for clinically significant disease. Automated diagnostic methods can assist ophthalmologists increase diagnosis accuracy using deep learning. Several research groups have highlighted various approaches. This paper proposes the use of new novel fundus preprocessing methods using pretrained transfer learning frameworks to create hybrid models to give higher diagnosis accuracy. The evaluations show that these novel methods in comparison to traditional imaging processing contribute to higher accuracy in classifying Plus disease, Stages of ROP and Zones. We achieve accuracy of 97.65% for Plus disease, 89.44% for Stage, 90.24% for Zones with limited training dataset.Comment: 10 pages, 4 figures, 7 tables. arXiv admin note: text overlap with arXiv:1904.08796 by other author

Deep Representation Learning with Limited Data for Biomedical Image Synthesis, Segmentation, and Detection

Biomedical imaging requires accurate expert annotation and interpretation that can aid medical staff and clinicians in automating differential diagnosis and solving underlying health conditions. With the advent of Deep learning, it has become a standard for reaching expert-level performance in non-invasive biomedical imaging tasks by training with large image datasets. However, with the need for large publicly available datasets, training a deep learning model to learn intrinsic representations becomes harder. Representation learning with limited data has introduced new learning techniques, such as Generative Adversarial Networks, Semi-supervised Learning, and Self-supervised Learning, that can be applied to various biomedical applications. For example, ophthalmologists use color funduscopy (CF) and fluorescein angiography (FA) to diagnose retinal degenerative diseases. However, fluorescein angiography requires injecting a dye, which can create adverse reactions in the patients. So, to alleviate this, a non-invasive technique needs to be developed that can translate fluorescein angiography from fundus images. Similarly, color funduscopy and optical coherence tomography (OCT) are also utilized to semantically segment the vasculature and fluid build-up in spatial and volumetric retinal imaging, which can help with the future prognosis of diseases. Although many automated techniques have been proposed for medical image segmentation, the main drawback is the model's precision in pixel-wise predictions. Another critical challenge in the biomedical imaging field is accurately segmenting and quantifying dynamic behaviors of calcium signals in cells. Calcium imaging is a widely utilized approach to studying subcellular calcium activity and cell function; however, large datasets have yielded a profound need for fast, accurate, and standardized analyses of calcium signals. For example, image sequences from calcium signals in colonic pacemaker cells ICC (Interstitial cells of Cajal) suffer from motion artifacts and high periodic and sensor noise, making it difficult to accurately segment and quantify calcium signal events. Moreover, it is time-consuming and tedious to annotate such a large volume of calcium image stacks or videos and extract their associated spatiotemporal maps. To address these problems, we propose various deep representation learning architectures that utilize limited labels and annotations to address the critical challenges in these biomedical applications. To this end, we detail our proposed semi-supervised, generative adversarial networks and transformer-based architectures for individual learning tasks such as retinal image-to-image translation, vessel and fluid segmentation from fundus and OCT images, breast micro-mass segmentation, and sub-cellular calcium events tracking from videos and spatiotemporal map quantification. We also illustrate two multi-modal multi-task learning frameworks with applications that can be extended to other domains of biomedical applications. The main idea is to incorporate each of these as individual modules to our proposed multi-modal frameworks to solve the existing challenges with 1) Fluorescein angiography synthesis, 2) Retinal vessel and fluid segmentation, 3) Breast micro-mass segmentation, and 4) Dynamic quantification of calcium imaging datasets

Task Decomposition and Synchronization for Semantic Biomedical Image Segmentation

Semantic segmentation is essentially important to biomedical image analysis. Many recent works mainly focus on integrating the Fully Convolutional Network (FCN) architecture with sophisticated convolution implementation and deep supervision. In this paper, we propose to decompose the single segmentation task into three subsequent sub-tasks, including (1) pixel-wise image segmentation, (2) prediction of the class labels of the objects within the image, and (3) classification of the scene the image belonging to. While these three sub-tasks are trained to optimize their individual loss functions of different perceptual levels, we propose to let them interact by the task-task context ensemble. Moreover, we propose a novel sync-regularization to penalize the deviation between the outputs of the pixel-wise segmentation and the class prediction tasks. These effective regularizations help FCN utilize context information comprehensively and attain accurate semantic segmentation, even though the number of the images for training may be limited in many biomedical applications. We have successfully applied our framework to three diverse 2D/3D medical image datasets, including Robotic Scene Segmentation Challenge 18 (ROBOT18), Brain Tumor Segmentation Challenge 18 (BRATS18), and Retinal Fundus Glaucoma Challenge (REFUGE18). We have achieved top-tier performance in all three challenges.Comment: IEEE Transactions on Medical Imagin