Weakly Supervised Multi-Task Learning for Cell Detection and Segmentation

Cell detection and segmentation is fundamental for all downstream analysis of digital pathology images. However, obtaining the pixel-level ground truth for single cell segmentation is extremely labor intensive. To overcome this challenge, we developed an end-to-end deep learning algorithm to perform both single cell detection and segmentation using only point labels. This is achieved through the combination of different task orientated point label encoding methods and a multi-task scheduler for training. We apply and validate our algorithm on PMS2 stained colon rectal cancer and tonsil tissue images. Compared to the state-of-the-art, our algorithm shows significant improvement in cell detection and segmentation without increasing the annotation efforts

Domain Adaptation-based Augmentation for Weakly Supervised Nuclei Detection

The detection of nuclei is one of the most fundamental components of computational pathology. Current state-of-the-art methods are based on deep learning, with the prerequisite that extensive labeled datasets are available. The increasing number of patient cohorts to be analyzed, the diversity of tissue stains and indications, as well as the cost of dataset labeling motivates the development of novel methods to reduce labeling effort across domains. We introduce in this work a weakly supervised 'inter-domain' approach that (i) performs stain normalization and unpaired image-to-image translation to transform labeled images on a source domain to synthetic labeled images on an unlabeled target domain and (ii) uses the resulting synthetic labeled images to train a detection network on the target domain. Extensive experiments show the superiority of the proposed approach against the state-of-the-art 'intra-domain' detection based on fully-supervised learning

Scribble2Label: Scribble-Supervised Cell Segmentation via Self-Generating Pseudo-Labels with Consistency

Segmentation is a fundamental process in microscopic cell image analysis. With the advent of recent advances in deep learning, more accurate and high-throughput cell segmentation has become feasible. However, most existing deep learning-based cell segmentation algorithms require fully annotated ground-truth cell labels, which are time-consuming and labor-intensive to generate. In this paper, we introduce Scribble2Label, a novel weakly-supervised cell segmentation framework that exploits only a handful of scribble annotations without full segmentation labels. The core idea is to combine pseudo-labeling and label filtering to generate reliable labels from weak supervision. For this, we leverage the consistency of predictions by iteratively averaging the predictions to improve pseudo labels. We demonstrate the performance of Scribble2Label by comparing it to several state-of-the-art cell segmentation methods with various cell image modalities, including bright-field, fluorescence, and electron microscopy. We also show that our method performs robustly across different levels of scribble details, which confirms that only a few scribble annotations are required in real-use cases.Comment: MICCAI 2020 accepte

Weakly-Supervised Segmentation for Disease Localization in Chest X-Ray Images

Deep Convolutional Neural Networks have proven effective in solving the task of semantic segmentation. However, their efficiency heavily relies on the pixel-level annotations that are expensive to get and often require domain expertise, especially in medical imaging. Weakly supervised semantic segmentation helps to overcome these issues and also provides explainable deep learning models. In this paper, we propose a novel approach to the semantic segmentation of medical chest X-ray images with only image-level class labels as supervision. We improve the disease localization accuracy by combining three approaches as consecutive steps. First, we generate pseudo segmentation labels of abnormal regions in the training images through a supervised classification model enhanced with a regularization procedure. The obtained activation maps are then post-processed and propagated into a second classification model-Inter-pixel Relation Network, which improves the boundaries between different object classes. Finally, the resulting pseudo-labels are used to train a proposed fully supervised segmentation model. We analyze the robustness of the presented method and test its performance on two distinct datasets: PASCAL VOC 2012 and SIIM-ACR Pneumothorax. We achieve significant results in the segmentation on both datasets using only image-level annotations. We show that this approach is applicable to chest X-rays for detecting an anomalous volume of air in the pleural space between the lung and the chest wall. Our code has been made publicly available.Comment: Accepted to AIME 202

Bounding boxes for weakly supervised segmentation: Global constraints get close to full supervision

We propose a novel weakly supervised learning segmentation based on several global constraints derived from box annotations. Particularly, we leverage a classical tightness prior to a deep learning setting via imposing a set of constraints on the network outputs. Such a powerful topological prior prevents solutions from excessive shrinking by enforcing any horizontal or vertical line within the bounding box to contain, at least, one pixel of the foreground region. Furthermore, we integrate our deep tightness prior with a global background emptiness constraint, guiding training with information outside the bounding box. We demonstrate experimentally that such a global constraint is much more powerful than standard cross-entropy for the background class. Our optimization problem is challenging as it takes the form of a large set of inequality constraints on the outputs of deep networks. We solve it with sequence of unconstrained losses based on a recent powerful extension of the log-barrier method, which is well-known in the context of interior-point methods. This accommodates standard stochastic gradient descent (SGD) for training deep networks, while avoiding computationally expensive and unstable Lagrangian dual steps and projections. Extensive experiments over two different public data sets and applications (prostate and brain lesions) demonstrate that the synergy between our global tightness and emptiness priors yield very competitive performances, approaching full supervision and outperforming significantly DeepCut. Furthermore, our approach removes the need for computationally expensive proposal generation. Our code is shared anonymously.Comment: Full paper, accepted for presentation at MIDL202

ACCL: Adversarial constrained-CNN loss for weakly supervised medical image segmentation

We propose adversarial constrained-CNN loss, a new paradigm of constrained-CNN loss methods, for weakly supervised medical image segmentation. In the new paradigm, prior knowledge is encoded and depicted by reference masks, and is further employed to impose constraints on segmentation outputs through adversarial learning with reference masks. Unlike pseudo label methods for weakly supervised segmentation, such reference masks are used to train a discriminator rather than a segmentation network, and thus are not required to be paired with specific images. Our new paradigm not only greatly facilitates imposing prior knowledge on network's outputs, but also provides stronger and higher-order constraints, i.e., distribution approximation, through adversarial learning. Extensive experiments involving different medical modalities, different anatomical structures, different topologies of the object of interest, different levels of prior knowledge and weakly supervised annotations with different annotation ratios is conducted to evaluate our ACCL method. Consistently superior segmentation results over the size constrained-CNN loss method have been achieved, some of which are close to the results of full supervision, thus fully verifying the effectiveness and generalization of our method. Specifically, we report an average Dice score of 75.4% with an average annotation ratio of 0.65%, surpassing the prior art, i.e., the size constrained-CNN loss method, by a large margin of 11.4%. Our codes are made publicly available at https://github.com/PengyiZhang/ACCL

Switching Loss for Generalized Nucleus Detection in Histopathology

The accuracy of deep learning methods for two foundational tasks in medical image analysis -- detection and segmentation -- can suffer from class imbalance. We propose a `switching loss' function that adaptively shifts the emphasis between foreground and background classes. While the existing loss functions to address this problem were motivated by the classification task, the switching loss is based on Dice loss, which is better suited for segmentation and detection. Furthermore, to get the most out the training samples, we adapt the loss with each mini-batch, unlike previous proposals that adapt once for the entire training set. A nucleus detector trained using the proposed loss function on a source dataset outperformed those trained using cross-entropy, Dice, or focal losses. Remarkably, without retraining on target datasets, our pre-trained nucleus detector also outperformed existing nucleus detectors that were trained on at least some of the images from the target datasets. To establish a broad utility of the proposed loss, we also confirmed that it led to more accurate ventricle segmentation in MRI as compared to the other loss functions. Our GPU-enabled pre-trained nucleus detection software is also ready to process whole slide images right out-of-the-box and is usably fast

NuClick: A Deep Learning Framework for Interactive Segmentation of Microscopy Images

Object segmentation is an important step in the workflow of computational pathology. Deep learning based models generally require large amount of labeled data for precise and reliable prediction. However, collecting labeled data is expensive because it often requires expert knowledge, particularly in medical imaging domain where labels are the result of a time-consuming analysis made by one or more human experts. As nuclei, cells and glands are fundamental objects for downstream analysis in computational pathology/cytology, in this paper we propose a simple CNN-based approach to speed up collecting annotations for these objects which requires minimum interaction from the annotator. We show that for nuclei and cells in histology and cytology images, one click inside each object is enough for NuClick to yield a precise annotation. For multicellular structures such as glands, we propose a novel approach to provide the NuClick with a squiggle as a guiding signal, enabling it to segment the glandular boundaries. These supervisory signals are fed to the network as auxiliary inputs along with RGB channels. With detailed experiments, we show that NuClick is adaptable to the object scale, robust against variations in the user input, adaptable to new domains, and delivers reliable annotations. An instance segmentation model trained on masks generated by NuClick achieved the first rank in LYON19 challenge. As exemplar outputs of our framework, we are releasing two datasets: 1) a dataset of lymphocyte annotations within IHC images, and 2) a dataset of segmented WBCs in blood smear images

Weakly Supervised Deep Nuclei Segmentation Using Partial Points Annotation in Histopathology Images

Nuclei segmentation is a fundamental task in histopathology image analysis. Typically, such segmentation tasks require significant effort to manually generate accurate pixel-wise annotations for fully supervised training. To alleviate such tedious and manual effort, in this paper we propose a novel weakly supervised segmentation framework based on partial points annotation, i.e., only a small portion of nuclei locations in each image are labeled. The framework consists of two learning stages. In the first stage, we design a semi-supervised strategy to learn a detection model from partially labeled nuclei locations. Specifically, an extended Gaussian mask is designed to train an initial model with partially labeled data. Then, selftraining with background propagation is proposed to make use of the unlabeled regions to boost nuclei detection and suppress false positives. In the second stage, a segmentation model is trained from the detected nuclei locations in a weakly-supervised fashion. Two types of coarse labels with complementary information are derived from the detected points and are then utilized to train a deep neural network. The fully-connected conditional random field loss is utilized in training to further refine the model without introducing extra computational complexity during inference. The proposed method is extensively evaluated on two nuclei segmentation datasets. The experimental results demonstrate that our method can achieve competitive performance compared to the fully supervised counterpart and the state-of-the-art methods while requiring significantly less annotation effort.Comment: 12 page

Semantic annotation for computational pathology: Multidisciplinary experience and best practice recommendations

Recent advances in whole slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence (AI) based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilize information embedded in pathology WSIs beyond what we obtain through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms which are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project