Cell instance segmentation in cytology images has significant importance for biology analysis and cancer screening, while remains challenging due to 1) the extensive overlapping translucent cell clusters that cause the ambiguous boundaries, and 2) the confusion of mimics and debris as nuclei. In this work, we proposed a De-overlapping Network (DoNet) in a decompose-and-recombined strategy. A Dual-path Region Segmentation Module (DRM) explicitly decomposes the cell clusters into intersection and complement regions, followed by a Semantic Consistency-guided Recombination Module (CRM) for integration. To further introduce the containment relationship of the nucleus in the cytoplasm, we design a Mask-guided Region Proposal Strategy (MRP) that integrates the cell attention maps for inner-cell instance prediction. We validate the proposed approach on ISBI2014 and CPS datasets. Experiments show that our proposed DoNet significantly outperforms other state-of-the-art (SOTA) cell instance segmentation methods. The code is available at https://github.com/DeepDoNet/DoNet.
Computational cytology is a critical, rapid-developing, yet challenging topic in the field of medical image computing which analyzes the digitized cytology image by computer-aided technologies for cancer screening. Recently, an increasing number of deep learning (DL) algorithms have made significant progress in medical image analysis, leading to the boosting publications of cytological studies. To investigate the advanced methods and comprehensive applications, we survey more than 120 publications of DL-based cytology image analysis in this article. We first introduce various deep learning methods, including fully supervised, weakly supervised, unsupervised, and transfer learning. Then, we systematically summarize the public datasets, evaluation metrics, versatile cytology image analysis applications including classification, detection, segmentation, and other related tasks. Finally, we discuss current challenges and potential research directions of computational cytology.
Deep learning has demonstrated radiograph screening performances that are comparable or superior to radiologists. However, recent studies show that deep models for thoracic disease classification usually show degraded performance when applied to external data. Such phenomena can be categorized into shortcut learning, where the deep models learn unintended decision rules that can fit the identically distributed training and test set but fail to generalize to other distributions. A natural way to alleviate this defect is explicitly indicating the lesions and focusing the model on learning the intended features. In this paper, we conduct extensive retrospective experiments to compare a popular thoracic disease classification model, CheXNet, and a thoracic lesion detection model, CheXDet. We first showed that the two models achieved similar image-level classification performance on the internal test set with no significant differences under many scenarios. Meanwhile, we found incorporating external training data even led to performance degradation for CheXNet. Then, we compared the models' internal performance on the lesion localization task and showed that CheXDet achieved significantly better performance than CheXNet even when given 80% less training data. By further visualizing the models' decision-making regions, we revealed that CheXNet learned patterns other than the target lesions, demonstrating its shortcut learning defect. Moreover, CheXDet achieved significantly better external performance than CheXNet on both the image-level classification task and the lesion localization task. Our findings suggest improving annotation granularity for training deep learning systems as a promising way to elevate future deep learning-based diagnosis systems for clinical usage.
Chest X-ray (CXR) is the most typical medical image worldwide to examine various thoracic diseases. Automatically localizing lesions from CXR is a promising way to alleviate radiologists' daily reading burden. However, CXR datasets often have numerous image-level annotations and scarce lesion-level annotations, and more often, without annotations. Thus far, unifying different supervision granularities to develop thoracic disease detection algorithms has not been comprehensively addressed. In this paper, we present OXnet, the first deep omni-supervised thoracic disease detection network to our best knowledge that uses as much available supervision as possible for CXR diagnosis. Besides fully supervised learning, to enable learning from weakly-annotated data, we guide the information from a global classification branch to the lesion localization branch by a dual attention alignment module. To further enhance global information learning, we impose intra-class compactness and inter-class separability with a global prototype alignment module. For unsupervised data learning, we extend the focal loss to be its soft form to distill knowledge from a teacher model. Extensive experiments show the proposed OXnet outperforms competitive methods with significant margins. Further, we investigate omni-supervision under various annotation granularities and corroborate OXnet is a promising choice to mitigate the plight of annotation shortage for medical image diagnosis.
Deep learning methods show promising results for overlapping cervical cell instance segmentation. However, in order to train a model with good generalization ability, voluminous pixel-level annotations are demanded which is quite expensive and time-consuming for acquisition. In this paper, we propose to leverage both labeled and unlabeled data for instance segmentation with improved accuracy by knowledge distillation. We propose a novel Mask-guided Mean Teacher framework with Perturbation-sensitive Sample Mining (MMT-PSM), which consists of a teacher and a student network during training. Two networks are encouraged to be consistent both in feature and semantic level under small perturbations. The teacher's self-ensemble predictions from $K$-time augmented samples are used to construct the reliable pseudo-labels for optimizing the student. We design a novel strategy to estimate the sensitivity to perturbations for each proposal and select informative samples from massive cases to facilitate fast and effective semantic distillation. In addition, to eliminate the unavoidable noise from the background region, we propose to use the predicted segmentation mask as guidance to enforce the feature distillation in the foreground region. Experiments show that the proposed method improves the performance significantly compared with the supervised method learned from labeled data only, and outperforms state-of-the-art semi-supervised methods.
Colorectal cancer (CRC) grading is typically carried out by assessing the degree of gland formation within histology images. To do this, it is important to consider the overall tissue micro-environment by assessing the cell-level information along with the morphology of the gland. However, current automated methods for CRC grading typically utilise small image patches and therefore fail to incorporate the entire tissue micro-architecture for grading purposes. To overcome the challenges of CRC grading, we present a novel cell-graph convolutional neural network (CGC-Net) that converts each large histology image into a graph, where each node is represented by a nucleus within the original image and cellular interactions are denoted as edges between these nodes according to node similarity. The CGC-Net utilises nuclear appearance features in addition to the spatial location of nodes to further boost the performance of the algorithm. To enable nodes to fuse multi-scale information, we introduce Adaptive GraphSage, which is a graph convolution technique that combines multi-level features in a data-driven way. Furthermore, to deal with redundancy in the graph, we propose a sampling technique that removes nodes in areas of dense nuclear activity. We show that modeling the image as a graph enables us to effectively consider a much larger image (around 16$\times$ larger) than traditional patch-based approaches and model the complex structure of the tissue micro-environment. We construct cell graphs with an average of over 3,000 nodes on a large CRC histology image dataset and report state-of-the-art results as compared to recent patch-based as well as contextual patch-based techniques, demonstrating the effectiveness of our method.
Cell instance segmentation in Pap smear image remains challenging due to the wide existence of occlusion among translucent cytoplasm in cell clumps. Conventional methods heavily rely on accurate nuclei detection results and are easily disturbed by miscellaneous objects. In this paper, we propose a novel Instance Relation Network (IRNet) for robust overlapping cell segmentation by exploring instance relation interaction. Specifically, we propose the Instance Relation Module to construct the cell association matrix for transferring information among individual cell-instance features. With the collaboration of different instances, the augmented features gain benefits from contextual information and improve semantic consistency. Meanwhile, we proposed a sparsity constrained Duplicate Removal Module to eliminate the misalignment between classification and localization accuracy for candidates selection. The largest cervical Pap smear (CPS) dataset with more than 8000 cell annotations in Pap smear image was constructed for comprehensive evaluation. Our method outperforms other methods by a large margin, demonstrating the effectiveness of exploring instance relation.
Accurate segmenting nuclei instances is a crucial step in computer-aided image analysis to extract rich features for cellular estimation and following diagnosis as well as treatment. While it still remains challenging because the wide existence of nuclei clusters, along with the large morphological variances among different organs make nuclei instance segmentation susceptible to over-/under-segmentation. Additionally, the inevitably subjective annotating and mislabeling prevent the network learning from reliable samples and eventually reduce the generalization capability for robustly segmenting unseen organ nuclei. To address these issues, we propose a novel deep neural network, namely Contour-aware Informative Aggregation Network (CIA-Net) with multi-level information aggregation module between two task-specific decoders. Rather than independent decoders, it leverages the merit of spatial and texture dependencies between nuclei and contour by bi-directionally aggregating task-specific features. Furthermore, we proposed a novel smooth truncated loss that modulates losses to reduce the perturbation from outliers. Consequently, the network can focus on learning from reliable and informative samples, which inherently improves the generalization capability. Experiments on the 2018 MICCAI challenge of Multi-Organ-Nuclei-Segmentation validated the effectiveness of our proposed method, surpassing all the other 35 competitive teams by a significant margin.
Cell nuclei detection and fine-grained classification have been fundamental yet challenging problems in histopathology image analysis. Due to the nuclei tiny size, significant inter-/intra-class variances, as well as the inferior image quality, previous automated methods would easily suffer from limited accuracy and robustness. In the meanwhile, existing approaches usually deal with these two tasks independently, which would neglect the close relatedness of them. In this paper, we present a novel method of sibling fully convolutional network with prior objectness interaction (called SFCN-OPI) to tackle the two tasks simultaneously and interactively using a unified end-to-end framework. Specifically, the sibling FCN branches share features in earlier layers while holding respective higher layers for specific tasks. More importantly, the detection branch outputs the objectness prior which dynamically interacts with the fine-grained classification sibling branch during the training and testing processes. With this mechanism, the fine-grained classification successfully focuses on regions with high confidence of nuclei existence and outputs the conditional probability, which in turn benefits the detection through back propagation. Extensive experiments on colon cancer histology images have validated the effectiveness of our proposed SFCN-OPI and our method has outperformed the state-of-the-art methods by a large margin.