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Data augmentation plays a crucial role in addressing the challenge of limited expert-annotated datasets in deep learning applications for retinal Optical Coherence Tomography (OCT) scans. This work exhaustively investigates the impact of various data augmentation techniques on retinal layer boundary and fluid segmentation. Our results reveal that their effectiveness significantly varies based on the dataset's characteristics and the amount of available labeled data. While the benefits of augmentation are not uniform - being more pronounced in scenarios with scarce data, particularly for transformation-based methods - the findings highlight the necessity of a strategic approach to data augmentation. It is essential to note that the effectiveness of data augmentation varies significantly depending on the characteristics of the dataset. The findings emphasize the need for a nuanced approach, considering factors like dataset characteristics, the amount of labelled data, and the choice of model architecture.

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

The use of multimodal imaging has led to significant improvements in the diagnosis and treatment of many diseases. Similar to clinical practice, some works have demonstrated the benefits of multimodal fusion for automatic segmentation and classification using deep learning-based methods. However, current segmentation methods are limited to fusion of modalities with the same dimensionality (e.g., 3D+3D, 2D+2D), which is not always possible, and the fusion strategies implemented by classification methods are incompatible with localization tasks. In this work, we propose a novel deep learning-based framework for the fusion of multimodal data with heterogeneous dimensionality (e.g., 3D+2D) that is compatible with localization tasks. The proposed framework extracts the features of the different modalities and projects them into the common feature subspace. The projected features are then fused and further processed to obtain the final prediction. The framework was validated on the following tasks: segmentation of geographic atrophy (GA), a late-stage manifestation of age-related macular degeneration, and segmentation of retinal blood vessels (RBV) in multimodal retinal imaging. Our results show that the proposed method outperforms the state-of-the-art monomodal methods on GA and RBV segmentation by up to 3.10% and 4.64% Dice, respectively., Comment: Accepted for publication in the IEEE Journal of Biomedical and Health Informatics (JBHI)

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback, Comment: 16 pages

The Segment Anything Model (SAM) has gained significant attention in the field of image segmentation due to its impressive capabilities and prompt-based interface. While SAM has already been extensively evaluated in various domains, its adaptation to retinal OCT scans remains unexplored. To bridge this research gap, we conduct a comprehensive evaluation of SAM and its adaptations on a large-scale public dataset of OCTs from RETOUCH challenge. Our evaluation covers diverse retinal diseases, fluid compartments, and device vendors, comparing SAM against state-of-the-art retinal fluid segmentation methods. Through our analysis, we showcase adapted SAM's efficacy as a powerful segmentation model in retinal OCT scans, although still lagging behind established methods in some circumstances. The findings highlight SAM's adaptability and robustness, showcasing its utility as a valuable tool in retinal OCT image analysis and paving the way for further advancements in this domain.

Deep learning has become a valuable tool for the automation of certain medical image segmentation tasks, significantly relieving the workload of medical specialists. Some of these tasks require segmentation to be performed on a subset of the input dimensions, the most common case being 3D-to-2D. However, the performance of existing methods is strongly conditioned by the amount of labeled data available, as there is currently no data efficient method, e.g. transfer learning, that has been validated on these tasks. In this work, we propose a novel convolutional neural network (CNN) and self-supervised learning (SSL) method for label-efficient 3D-to-2D segmentation. The CNN is composed of a 3D encoder and a 2D decoder connected by novel 3D-to-2D blocks. The SSL method consists of reconstructing image pairs of modalities with different dimensionality. The approach has been validated in two tasks with clinical relevance: the en-face segmentation of geographic atrophy and reticular pseudodrusen in optical coherence tomography. Results on different datasets demonstrate that the proposed CNN significantly improves the state of the art in scenarios with limited labeled data by up to 8% in Dice score. Moreover, the proposed SSL method allows further improvement of this performance by up to 23%, and we show that the SSL is beneficial regardless of the network architecture., Comment: To appear in MICCAI 2023. Code: https://github.com/j-morano/multimodal-ssl-fpn

The early detection of glaucoma is essential in preventing visual impairment. Artificial intelligence (AI) can be used to analyze color fundus photographs (CFPs) in a cost-effective manner, making glaucoma screening more accessible. While AI models for glaucoma screening from CFPs have shown promising results in laboratory settings, their performance decreases significantly in real-world scenarios due to the presence of out-of-distribution and low-quality images. To address this issue, we propose the Artificial Intelligence for Robust Glaucoma Screening (AIROGS) challenge. This challenge includes a large dataset of around 113,000 images from about 60,000 patients and 500 different screening centers, and encourages the development of algorithms that are robust to ungradable and unexpected input data. We evaluated solutions from 14 teams in this paper, and found that the best teams performed similarly to a set of 20 expert ophthalmologists and optometrists. The highest-scoring team achieved an area under the receiver operating characteristic curve of 0.99 (95% CI: 0.98-0.99) for detecting ungradable images on-the-fly. Additionally, many of the algorithms showed robust performance when tested on three other publicly available datasets. These results demonstrate the feasibility of robust AI-enabled glaucoma screening., Comment: 19 pages, 8 figures, 3 tables

Bruch's membrane (BM) segmentation on optical coherence tomography (OCT) is a pivotal step for the diagnosis and follow-up of age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world. Automated BM segmentation methods exist, but they usually do not account for the anatomical coherence of the results, neither provide feedback on the confidence of the prediction. These factors limit the applicability of these systems in real-world scenarios. With this in mind, we propose an end-to-end deep learning method for automated BM segmentation in AMD patients. An Attention U-Net is trained to output a probability density function of the BM position, while taking into account the natural curvature of the surface. Besides the surface position, the method also estimates an A-scan wise uncertainty measure of the segmentation output. Subsequently, the A-scans with high uncertainty are interpolated using thin plate splines (TPS). We tested our method with ablation studies on an internal dataset with 138 patients covering all three AMD stages, and achieved a mean absolute localization error of 4.10 um. In addition, the proposed segmentation method was compared against the state-of-the-art methods and showed a superior performance on an external publicly available dataset from a different patient cohort and OCT device, demonstrating strong generalization ability.

Optical coherence tomography (OCT) is a non-invasive 3D modality widely used in ophthalmology for imaging the retina. Achieving automated, anatomically coherent retinal layer segmentation on OCT is important for the detection and monitoring of different retinal diseases, like Age-related Macular Disease (AMD) or Diabetic Retinopathy. However, the majority of state-of-the-art layer segmentation methods are based on purely supervised deep-learning, requiring a large amount of pixel-level annotated data that is expensive and hard to obtain. With this in mind, we introduce a semi-supervised paradigm into the retinal layer segmentation task that makes use of the information present in large-scale unlabeled datasets as well as anatomical priors. In particular, a novel fully differentiable approach is used for converting surface position regression into a pixel-wise structured segmentation, allowing to use both 1D surface and 2D layer representations in a coupled fashion to train the model. In particular, these 2D segmentations are used as anatomical factors that, together with learned style factors, compose disentangled representations used for reconstructing the input image. In parallel, we propose a set of anatomical priors to improve network training when a limited amount of labeled data is available. We demonstrate on the real-world dataset of scans with intermediate and wet-AMD that our method outperforms state-of-the-art when using our full training set, but more importantly largely exceeds state-of-the-art when it is trained with a fraction of the labeled data., Comment: Accepted at MICCAI 2022

The development of automatic tools for early glaucoma diagnosis with color fundus photographs can significantly reduce the impact of this disease. However, current state-of-the-art solutions are not robust to real-world scenarios, providing over-confident predictions for out-of-distribution cases. With this in mind, we propose a model based on the Dirichlet distribution that allows to obtain class-wise probabilities together with an uncertainty estimation without exposure to out-of-distribution cases. We demonstrate our approach on the AIROGS challenge. At the start of the final test phase (8 Feb. 2022), our method had the highest average score among all submissions., Comment: Submitted to ISBI 2022

Breast cancer is the most common malignancy in women, being responsible for more than half a million deaths every year. As such, early and accurate diagnosis is of paramount importance. Human expertise is required to diagnose and correctly classify breast cancer and define appropriate therapy, which depends on the evaluation of the expression of different biomarkers such as the transmembrane protein receptor HER2. This evaluation requires several steps, including special techniques such as immunohistochemistry or in situ hybridization to assess HER2 status. With the goal of reducing the number of steps and human bias in diagnosis, the HEROHE Challenge was organized, as a parallel event of the 16th European Congress on Digital Pathology, aiming to automate the assessment of the HER2 status based only on hematoxylin and eosin stained tissue sample of invasive breast cancer. Methods to assess HER2 status were presented by 21 teams worldwide and the results achieved by some of the proposed methods open potential perspectives to advance the state-of-the-art.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly, time-consuming and prone to variability. This has fueled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules but its application to clinical routine is challenging. In this study, a new database for the development and testing of pulmonary nodule computer-aided strategies is presented which intends to complement current databases by giving additional focus to radiologist variability and local clinical reality. State-of-the-art nodule detection, segmentation and characterization methods are tested and compared to manual annotations as well as collaborative strategies combining multiple radiologists and radiologists and computer-aided systems. It is shown that state-of-the-art methodologies can determine a patient's follow-up recommendation as accurately as a radiologist, though the nodule detection method used shows decreased performance in this database.

Diabetic retinopathy (DR) grading is crucial in determining the adequate treatment and follow up of patients, but the screening process can be tiresome and prone to errors. Deep learning approaches have shown promising performance as computer-aided diagnosis(CAD) systems, but their black-box behaviour hinders the clinical application. We propose DR$\vert$GRADUATE, a novel deep learning-based DR grading CAD system that supports its decision by providing a medically interpretable explanation and an estimation of how uncertain that prediction is, allowing the ophthalmologist to measure how much that decision should be trusted. We designed DR$\vert$GRADUATE taking into account the ordinal nature of the DR grading problem. A novel Gaussian-sampling approach built upon a Multiple Instance Learning framework allow DR$\vert$GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR$\vert$GRADUATE was trained on the Kaggle training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (QWK) between 0.71 and 0.84 was achieved in five different datasets. We show that high QWK values occur for images with low prediction uncertainty, thus indicating that this uncertainty is a valid measure of the predictions' quality. Further, bad quality images are generally associated with higher uncertainties, showing that images not suitable for diagnosis indeed lead to less trustworthy predictions. Additionally, tests on unfamiliar medical image data types suggest that DR$\vert$GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR$\vert$GRADUATE as a second-opinion system in DR severity grading., Comment: Published at Medical Image Analysis (Elsevier). Publication licensed under the Creative Commons CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. Figures are compressed due to file size constraints

Early diagnosis of lung cancer via computed tomography can significantly reduce the morbidity and mortality rates associated with the pathology. However, search lung nodules is a high complexity task, which affects the success of screening programs. Whilst computer-aided detection systems can be used as second observers, they may bias radiologists and introduce significant time overheads. With this in mind, this study assesses the potential of using gaze information for integrating automatic detection systems in the clinical practice. For that purpose, 4 radiologists were asked to annotate 20 scans from a public dataset while being monitored by an eye tracker device and an automatic lung nodule detection system was developed. Our results show that radiologists follow a similar search routine and tend to have lower fixation periods in regions where finding errors occur. The overall detection sensitivity of the specialists was 0.67$\pm$0.07, whereas the system achieved 0.69. Combining the annotations of one radiologist with the automatic system significantly improves the detection performance to similar levels of two annotators. Likewise, combining the findings of radiologist with the detection algorithm only for low fixation regions still significantly improves the detection sensitivity without increasing the number of false-positives. The combination of the automatic system with the gaze information allows to mitigate possible errors of the radiologist without some of the issues usually associated with automatic detection system., Comment: Submitted to IEEE Transactions on Biomedical Engineering (TBME)