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

Retinal Microaneurysms Detection Using Adversarial Pre-training With Unlabeled Multimodal Images

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The detection of retinal microaneurysms is crucial for the early detection of important diseases such as diabetic retinopathy. However, the detection of these lesions in retinography, the most widely available retinal imaging modality, remains a very challenging task. This is mainly due to the tiny size and low contrast of the microaneurysms in the images. Consequently, the automated detection of microaneurysms usually relies on extensive ad-hoc processing. In this regard, although microaneurysms can be more easily detected using fluorescein angiography, this alternative imaging modality is invasive and not adequate for regular preventive screening. In this work, we propose a novel deep learning methodology that takes advantage of unlabeled multimodal image pairs for improving the detection of microaneurysms in retinography. In particular, we propose a novel adversarial multimodal pre-training consisting in the prediction of fluorescein angiography from retinography using generative adversarial networks. This pre-training allows learning about the retina and the microaneurysms without any manually annotated data. Additionally, we also propose to approach the microaneurysms detection as a heatmap regression, which allows an efficient detection and precise localization of multiple microaneurysms. To validate and analyze the proposed methodology, we perform an exhaustive experimentation on different public datasets. Additionally, we provide relevant comparisons against different state-of-the-art approaches. The results show a satisfactory performance of the proposal, achieving an Average Precision of 64.90%, 31.36%, and 33.55% in the E-Ophtha, ROC, and DDR public datasets. Overall, the proposed approach outperforms existing deep learning alternatives while providing a more straightforward detection method that can be effectively applied to raw unprocessed retinal images.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Xunta de Galicia, Spain and the European Social Fund (ESF) of the EU through the predoctoral grant contract ref. ED481A-2017/328; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Cultura, Educación e Universidade, Xunta de Galicia , through the ERDF (80%) and Secretaría Xeral de Universidades (20%). Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED481A-2017/328Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Generative adversarial networks in ophthalmology: what are these and how can they be used?

PURPOSE OF REVIEW: The development of deep learning (DL) systems requires a large amount of data, which may be limited by costs, protection of patient information and low prevalence of some conditions. Recent developments in artificial intelligence techniques have provided an innovative alternative to this challenge via the synthesis of biomedical images within a DL framework known as generative adversarial networks (GANs). This paper aims to introduce how GANs can be deployed for image synthesis in ophthalmology and to discuss the potential applications of GANs-produced images. RECENT FINDINGS: Image synthesis is the most relevant function of GANs to the medical field, and it has been widely used for generating 'new' medical images of various modalities. In ophthalmology, GANs have mainly been utilized for augmenting classification and predictive tasks, by synthesizing fundus images and optical coherence tomography images with and without pathologies such as age-related macular degeneration and diabetic retinopathy. Despite their ability to generate high-resolution images, the development of GANs remains data intensive, and there is a lack of consensus on how best to evaluate the outputs produced by GANs. SUMMARY: Although the problem of artificial biomedical data generation is of great interest, image synthesis by GANs represents an innovation with yet unclear relevance for ophthalmology

CAD system for early diagnosis of diabetic retinopathy based on 3D extracted imaging markers.

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate delineation of retinal layers, enabling better understanding of the anatomical structure and more effective surgical interventions. Moreover, real-time guidance systems can be developed to assist surgeons during procedures, improving overall patient outcomes. The second contribution of this dissertation is the introduction of a novel computeraided diagnosis (CAD) system for precise identification of diabetic retinopathy. The CAD system utilizes 3D-OCT imaging and employs an innovative approach that extracts two distinct features: first-order reflectivity and 3D thickness. These features are then fused and used to train and test a neural network classifier. The proposed CAD system exhibits promising results, surpassing other machine learning and deep learning algorithms commonly employed in DR detection. This demonstrates the effectiveness of the comprehensive analysis approach employed by the CAD system, which considers both low-level and high-level data from the 3D retinal layers. The CAD system presents a groundbreaking contribution to the field, as it goes beyond conventional methods, optimizing backpropagated neural networks to integrate multiple levels of information effectively. By achieving superior performance, the proposed CAD system showcases its potential in accurately diagnosing DR and aiding in the prevention of vision loss. In conclusion, this dissertation presents novel approaches for the segmentation of retinal layers and the diagnosis of diabetic retinopathy. The proposed methods exhibit significant improvements in accuracy, speed, and performance compared to existing techniques, opening new avenues for clinical applications and advancements in the field of ophthalmology. By addressing future research directions, such as testing on larger datasets, exploring alternative algorithms, and incorporating user feedback, the proposed methods can be further refined and developed into robust, accurate, and clinically valuable tools for diagnosing and monitoring retinal diseases