We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzhen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform.

Collecting large-scale medical datasets with fully annotated samples for training of deep networks is prohibitively expensive, especially for 3D volume data. Recent breakthroughs in self-supervised learning (SSL) offer the ability to overcome the lack of labeled training samples by learning feature representations from unlabeled data. However, most current SSL techniques in the medical field have been designed for either 2D images or 3D volumes. In practice, this restricts the capability to fully leverage unlabeled data from numerous sources, which may include both 2D and 3D data. Additionally, the use of these pre-trained networks is constrained to downstream tasks with compatible data dimensions. In this paper, we propose a novel framework for unsupervised joint learning on 2D and 3D data modalities. Given a set of 2D images or 2D slices extracted from 3D volumes, we construct an SSL task based on a 2D contrastive clustering problem for distinct classes. The 3D volumes are exploited by computing vectored embedding at each slice and then assembling a holistic feature through deformable self-attention mechanisms in Transformer, allowing incorporating long-range dependencies between slices inside 3D volumes. These holistic features are further utilized to define a novel 3D clustering agreement-based SSL task and masking embedding prediction inspired by pre-trained language models. Experiments on downstream tasks, such as 3D brain segmentation, lung nodule detection, 3D heart structures segmentation, and abnormal chest X-ray detection, demonstrate the effectiveness of our joint 2D and 3D SSL approach. We improve plain 2D Deep-ClusterV2 and SwAV by a significant margin and also surpass various modern 2D and 3D SSL approaches.

Obtaining large pre-trained models that can be fine-tuned to new tasks with limited annotated samples has remained an open challenge for medical imaging data. While pre-trained networks on ImageNet and vision-language foundation models trained on web-scale data are the prevailing approaches, their effectiveness on medical tasks is limited due to the significant domain shift between natural and medical images. To bridge this gap, we introduce LVM-Med, the first family of deep networks trained on large-scale medical datasets. We have collected approximately 1.3 million medical images from 55 publicly available datasets, covering a large number of organs and modalities such as CT, MRI, X-ray, and Ultrasound. We benchmark several state-of-the-art self-supervised algorithms on this dataset and propose a novel self-supervised contrastive learning algorithm using a graph-matching formulation. The proposed approach makes three contributions: (i) it integrates prior pair-wise image similarity metrics based on local and global information; (ii) it captures the structural constraints of feature embeddings through a loss function constructed through a combinatorial graph-matching objective, and (iii) it can be trained efficiently end-to-end using modern gradient-estimation techniques for black-box solvers. We thoroughly evaluate the proposed LVM-Med on 15 downstream medical tasks ranging from segmentation and classification to object detection, and both for the in and out-of-distribution settings. LVM-Med empirically outperforms a number of state-of-the-art supervised, self-supervised, and foundation models. For challenging tasks such as Brain Tumor Classification or Diabetic Retinopathy Grading, LVM-Med improves previous vision-language models trained on 1 billion masks by 6-7% while using only a ResNet-50.

Federated Learning (FL) could solve the challenges of training AI models on large datasets for medical imaging due to data privacy and ownership concerns by allowing collaborative training without the need for sharing raw data. This Special Issue on Federated Learning for Medical Imaging features papers covering FL-related topics and discussing their implications for healthcare and medical imaging. The included articles focus on a broad range of federated scenarios and applications, such as semi-supervised and self-supervised learning, histopathology, image reconstruction, graph neural networks, privacy preservation, active learning, data auditing, multi-task learning, personalization, and swarm learning. The importance of training unbiased, privacy-preserving, and generalizable AI models that have the potential to be translated into clinical practice increases the need for collaborative training techniques such as FL. The articles included in this Special Issue have moved the needle markedly forward in this regard.

Chemical staining of the blood smears is one of the crucial components of blood analysis. It is an expensive, lengthy and sensitive process, often prone to produce slight variations in colour and seen structures due to a lack of unified protocols across laboratories. Even though the current developments in deep generative modeling offer an opportunity to replace the chemical process with a digital one, there are specific safety-ensuring requirements due to the severe consequences of mistakes in a medical setting. Therefore digital staining system would profit from an additional confidence estimation quantifying the quality of the digitally stained white blood cell. To this aim, during the staining generation, we disentangle the latent space of the Generative Adversarial Network, obtaining separate representation s of the white blood cell and the staining. We estimate the generated image's confidence of white blood cell structure and staining quality by corrupting these representations with noise and quantifying the information retained between multiple outputs. We show that confidence estimated in this way correlates with image quality measured in terms of LPIPS values calculated for the generated and ground truth stained images. We validate our method by performing digital staining of images captured with a Differential Inference Contrast microscope on a dataset composed of white blood cells of 24 patients. The high absolute value of the correlation between our confidence score and LPIPS demonstrates the effectiveness of our method, opening the possibility of predicting the quality of generated output and ensuring trustworthiness in medical safety-critical setup.

Federated Learning (FL) is a novel approach enabling several clients holding sensitive data to collaboratively train machine learning models, without centralizing data. The cross-silo FL setting corresponds to the case of few ($2$--$50$) reliable clients, each holding medium to large datasets, and is typically found in applications such as healthcare, finance, or industry. While previous works have proposed representative datasets for cross-device FL, few realistic healthcare cross-silo FL datasets exist, thereby slowing algorithmic research in this critical application. In this work, we propose a novel cross-silo dataset suite focused on healthcare, FLamby (Federated Learning AMple Benchmark of Your cross-silo strategies), to bridge the gap between theory and practice of cross-silo FL.FLamby encompasses 7 healthcare datasets with natural splits, covering multiple tasks, modalities, and data volumes, each accompanied with baseline training code. As an illustration, we additionally benchmark standard FL algorithms on all datasets.Our flexible and modular suite allows researchers to easily download datasets, reproduce results and re-use the different components for their research. FLamby is available at~\url{www.github.com/owkin/flamby}.

Abstract Medical image segmentation is one of the major challenges addressed by machine learning methods. However, these methods profoundly depend on a large amount of annotated data, which is expensive and time‐consuming. Semi‐supervised learning (SSL) approaches this by leveraging an abundant amount of unlabeled data. Recently, MixUp regularizer has been introduced to SSL methods by augmenting the model with new data points through linear interpolation at the input space. While this provides the model with new data, it is limited and may lead to inconsistent soft labels. It is argued that the linear interpolation at different representations provides the network with novel training signals and overcomes the inconsistency of the soft labels. This paper proposes ROAM as an SSL method that explores the manifold and performs linear interpolation on randomly selected layers to generate virtual data that has never been seen before, which encourages the network to be less confident for interpolated points. Hence it avoids overfitting, enhances the generalization, and shows less sensitivity to the domain shift. Extensive experiments are conducted on publicl datasets on whole‐brain and lung segmentation. ROAM achieves state‐of‐the‐art results in fully supervised (89.5%) and semi‐supervised (87.0%) settings with relative improvements up to 2.40% and 16.50%, respectively.

Skin cancer is one of the most deadly cancers worldwide. Yet, it can be\nreduced by early detection. Recent deep-learning methods have shown a\ndermatologist-level performance in skin cancer classification. Yet, this\nsuccess demands a large amount of centralized data, which is oftentimes not\navailable. Federated learning has been recently introduced to train machine\nlearning models in a privacy-preserved distributed fashion demanding annotated\ndata at the clients, which is usually expensive and not available, especially\nin the medical field. To this end, we propose FedPerl, a semi-supervised\nfederated learning method that utilizes peer learning from social sciences and\nensemble averaging from committee machines to build communities and encourage\nits members to learn from each other such that they produce more accurate\npseudo labels. We also propose the peer anonymization (PA) technique as a core\ncomponent of FedPerl. PA preserves privacy and reduces the communication cost\nwhile maintaining the performance without additional complexity. We validated\nour method on 38,000 skin lesion images collected from 4 publicly available\ndatasets. FedPerl achieves superior performance over the baselines and\nstate-of-the-art SSFL by 15.8%, and 1.8% respectively. Further, FedPerl shows\nless sensitivity to noisy clients.

Stain virtualization is an application with growing interest in digital pathology allowing simulation of stained tissue images thus saving lab and tissue resources. Thanks to the success of Generative Adversarial Networks (GANs) and the progress of unsupervised learning, unsupervised style transfer GANs have been successfully used to generate realistic, clinically meaningful and interpretable images. The large size of high resolution Whole Slide Images (WSIs) presents an additional computational challenge. This makes tilewise processing necessary during training and inference of deep learning networks. Instance normalization has a substantial positive effect in style transfer GAN applications but with tilewise inference, it has the tendency to cause a tiling artifact in reconstructed WSIs. In this paper we propose a novel perceptual embedding consistency (PEC) loss forcing the network to learn color, contrast and brightness invariant features in the latent space and hence substantially reducing the aforementioned tiling artifact. Our approach results in more seamless reconstruction of the virtual WSIs. We validate our method quantitatively by comparing the virtually generated images to their corresponding consecutive real stained images. We compare our results to state-of-the-art unsupervised style transfer methods and to the measures obtained from consecutive real stained tissue slide images. We demonstrate our hypothesis about the effect of the PEC loss by comparing model robustness to color, contrast and brightness perturbations and visualizing bottleneck embeddings. We validate the robustness of the bottleneck feature maps by measuring their sensitivity to the different perturbations and using them in a tumor segmentation task. Additionally, we propose a preliminary validation of the virtual staining application by comparing interpretation of 2 pathologists on real and virtual tiles and inter-pathologist agreement.

This paper addresses digital staining and classification of the unstained white blood cell images obtained with a differential contrast microscope. We have data coming from multiple domains that are partially labeled and partially matching across the domains. Using unstained images removes time-consuming staining procedures and could facilitate and automatize comprehensive diagnostics. To this aim, we propose a method that translates unstained images to realistically looking stained images preserving the inter-cellular structures, crucial for the medical experts to perform classification. We achieve better structure preservation by adding auxiliary tasks of segmentation and direct reconstruction. Segmentation enforces that the network learns to generate correct nucleus and cytoplasm shape, while direct reconstruction enforces reliable translation between the matching images across domains. Besides, we build a robust domain agnostic latent space by injecting the target domain label directly to the generator, i.e., bypassing the encoder. It allows the encoder to extract features independently of the target domain and enables an automated domain invariant classification of the white blood cells. We validated our method on a large dataset composed of leukocytes of 24 patients, achieving state-of-the-art performance on both digital staining and classification tasks.

Deep learning techniques are recently being used in fundus image analysis and diabetic retinopathy detection. Microaneurysms are important indicators of diabetic retinopathy progression. The authors introduce a two‐stage deep learning approach for microaneurysms segmentation using multiple scales of the input with selective sampling and embedding triplet loss. The proposed approach facilitates a region proposal fully convolutional neural network trained on segmented patches and a patch‐wise refinement network for improving the results suggested by the first stage hypothesis. To enhance the discriminative power of the second stage refinement network, the authors use triplet embedding loss with a selective sampling routine that dynamically assigns sampling probabilities to the oversampled class patches. This approach introduces a relative improvement over the vanilla fully convolutional neural network on the Indian Diabetic Retinopathy Image Data set segmentation data set. The proposed segmentation is incorporated in a classification model to solve two downstream tasks for diabetic retinopathy detection and referable diabetic retinopathy detection. The classification tasks are trained on the Kaggle diabetic retinopathy challenge data set and evaluated on the Messidor data. The authors show that adding the segmentation enhances the classification performance and achieves comparable performance to the state‐of‐the‐art models.

Chest X-ray radiography is one of the earliest medical imaging technologies and remains one of the most widely-used for diagnosis, screening, and treatment follow up of diseases related to lungs and heart. The literature in this field of research reports many interesting studies dealing with the challenging tasks of bone suppression and organ segmentation but performed separately, limiting any learning that comes with the consolidation of parameters that could optimize both processes. This study, and for the first time, introduces a multitask deep learning model that generates simultaneously the bone-suppressed image and the organ-segmented image, enhancing the accuracy of tasks, minimizing the number of parameters needed by the model and optimizing the processing time, all by exploiting the interplay between the network parameters to benefit the performance of both tasks. The architectural design of this model, which relies on a conditional generative adversarial network, reveals the process on how the wellestablished pix2pix network (image-to-image network) is modified to fit the need for multitasking and extending it to the new image-to-images architecture. The developed source code of this multitask model is shared publicly on Github as the first attempt for providing the two-task pix2pix extension, a supervised/paired/aligned/registered image-to-images translation which would be useful in many multitask applications. Dilated convolutions are also used to improve the results through a more effective receptive field assessment. The comparison with state-of-the-art al-gorithms along with ablation study and a demonstration video1 are provided to evaluate the efficacy and gauge the merits of the proposed approach.

In this work, we propose a method for object recognition and pose estimation from depth images using convolutional neural networks. Previous methods addressing this problem rely on manifold learning to learn low dimensional viewpoint descriptors and employ them in a nearest neighbor search on an estimated descriptor space. In comparison we create an efficient multi-task learning framework combining manifold descriptor learning and pose regression. By combining the strengths of manifold learning using triplet loss and pose regression, we could either estimate the pose directly reducing the complexity compared to NN search, or use the learned descriptor for the NN descriptor matching. By in depth experimental evaluation of the novel loss function we observed that the view descriptors learned by the network are much more discriminative resulting in almost 30% increase regarding relative pose accuracy compared to related works. On the other hand, regarding directly regressed poses we obtained important improvement compared to simple pose regression. By leveraging the advantages of both manifold learning and regression tasks, we are able to improve the current state-of-the-art for object recognition and pose retrieval.

Precise reconstruction of 3D volumes from X-ray projections requires precisely pre-calibrated systems where accurate knowledge of the systems geometric parameters is known ahead. However, when dealing with mobile X-ray devices such calibration parameters are unknown. Joint estimation of the systems calibration parameters and 3d reconstruction is a heavily unconstrained problem, especially when the projections are arbitrary. In industrial applications, that we target here, nominal CAD models of the object to be reconstructed are usually available. We rely on this prior information and employ Deep Learning to learn the mapping between simulated X-ray projections and its pose. Moreover, we introduce the reconstruction loss in addition to the pose loss to further improve the reconstruction quality. Finally, we demonstrate the generalization capabilities of our method in case where poses can be learned on instances of the objects belonging to the same class, allowing pose estimation of unseen objects from the same category, thus eliminating the need for the actual CAD model. We performed exhaustive evaluation demonstrating the quality of our results on both synthetic and real data.

The lack of publicly available ground-truth data has been identified as the major challenge for transferring recent developments in deep learning to the biomedical imaging domain. Though crowdsourcing has enabled annotation of large scale databases for real world images, its application for biomedical purposes requires a deeper understanding and hence, more precise definition of the actual annotation task. The fact that expert tasks are being outsourced to non-expert users may lead to noisy annotations introducing disagreement between users. Despite being a valuable resource for learning annotation models from crowdsourcing, conventional machine-learning methods may have difficulties dealing with noisy annotations during training. In this manuscript, we present a new concept for learning from crowds that handle data aggregation directly as part of the learning process of the convolutional neural network (CNN) via additional crowdsourcing layer (AggNet). Besides, we present an experimental study on learning from crowds designed to answer the following questions. 1) Can deep CNN be trained with data collected from crowdsourcing? 2) How to adapt the CNN to train on multiple types of annotation datasets (ground truth and crowd-based)? 3) How does the choice of annotation and aggregation affect the accuracy? Our experimental setup involved Annot8, a self-implemented web-platform based on Crowdflower API realizing image annotation tasks for a publicly available biomedical image database. Our results give valuable insights into the functionality of deep CNN learning from crowd annotations and prove the necessity of data aggregation integration.

Staining and scanning of tissue samples for microscopic examination is fraught with undesirable color variations arising from differences in raw materials and manufacturing techniques of stain vendors, staining protocols of labs, and color responses of digital scanners. When comparing tissue samples, color normalization and stain separation of the tissue images can be helpful for both pathologists and software. Techniques that are used for natural images fail to utilize structural properties of stained tissue samples and produce undesirable color distortions. The stain concentration cannot be negative. Tissue samples are stained with only a few stains and most tissue regions are characterized by at most one effective stain. We model these physical phenomena that define the tissue structure by first decomposing images in an unsupervised manner into stain density maps that are sparse and non-negative. For a given image, we combine its stain density maps with stain color basis of a pathologist-preferred target image, thus altering only its color while preserving its structure described by the maps. Stain density correlation with ground truth and preference by pathologists were higher for images normalized using our method when compared to other alternatives. We also propose a computationally faster extension of this technique for large whole-slide images that selects an appropriate patch sample instead of using the entire image to compute the stain color basis.

Cryo-Electron Tomography is a leading imaging technique in structural biology, which is capable of acquiring two-dimensional projections of cellular structures at high resolution and close-to-native state. Due to the limited electron dose the resulting projections exhibit extremely low SNR and contrast. The 3D structure is then reconstructed and passed through a number of post-processing steps including de-noising and sub-tomogram averaging to provide a better understanding and interpretation. As CET is mainly used for imaging fine scale structures, any denoising method applied to CET images should be scale selective and in particular be able to preserve such fine scale structures. In this context, we propose a new denoising framework based on regularized graph spectral filtering with a full control of scale-space and global consistency. Using the gold-standard metrics, we show that our denoising algorithm significantly outperforms the state-of-the-art methods such as NAD, NLM and RGF in terms of noise removal and structure preservation.