Huangjing Lin

Zhizhong Chai, Luyang Luo, Huangjing Lin et al.

Deep learning (DL)-based rib fracture detection has shown promise of playing an important role in preventing mortality and improving patient outcome. Normally, developing DL-based object detection models requires a huge amount of bounding box annotation. However, annotating medical data is time-consuming and expertise-demanding, making obtaining a large amount of fine-grained annotations extremely infeasible. This poses a pressing need {for} developing label-efficient detection models to alleviate radiologists' labeling burden. To tackle this challenge, the literature on object detection has witnessed an increase of weakly-supervised and semi-supervised approaches, yet still lacks a unified framework that leverages various forms of fully-labeled, weakly-labeled, and unlabeled data. In this paper, we present a novel omni-supervised object detection network, ORF-Netv2, to leverage as much available supervision as possible. Specifically, a multi-branch omni-supervised detection head is introduced with each branch trained with a specific type of supervision. A co-training-based dynamic label assignment strategy is then proposed to enable flexible and robust learning from the weakly-labeled and unlabeled data. Extensive evaluation was conducted for the proposed framework with three rib fracture datasets on both chest CT and X-ray. By leveraging all forms of supervision, ORF-Netv2 achieves mAPs of 34.7, 44.7, and 19.4 on the three datasets, respectively, surpassing the baseline detector which uses only box annotations by mAP gains of 3.8, 4.8, and 5.0, respectively. Furthermore, ORF-Netv2 consistently outperforms other competitive label-efficient methods over various scenarios, showing a promising framework for label-efficient fracture detection. The code is available at: https://github.com/zhizhongchai/ORF-Net.

Zhizhong Chai, Huangjing Lin, Luyang Luo et al.

Most of the existing object detection works are based on the bounding box annotation: each object has a precise annotated box. However, for rib fractures, the bounding box annotation is very labor-intensive and time-consuming because radiologists need to investigate and annotate the rib fractures on a slice-by-slice basis. Although a few studies have proposed weakly-supervised methods or semi-supervised methods, they could not handle different forms of supervision simultaneously. In this paper, we proposed a novel omni-supervised object detection network, which can exploit multiple different forms of annotated data to further improve the detection performance. Specifically, the proposed network contains an omni-supervised detection head, in which each form of annotation data corresponds to a unique classification branch. Furthermore, we proposed a dynamic label assignment strategy for different annotated forms of data to facilitate better learning for each branch. Moreover, we also design a confidence-aware classification loss to emphasize the samples with high confidence and further improve the model's performance. Extensive experiments conducted on the testing dataset show our proposed method outperforms other state-of-the-art approaches consistently, demonstrating the efficacy of deep omni-supervised learning on improving rib fracture detection performance.

Runsheng Liu, Hao Jiang, Yanning Zhou et al.

Instance segmentation plays a vital role in the morphological quantification of biomedical entities such as tissues and cells, enabling precise identification and delineation of different structures. Current methods often address the challenges of touching, overlapping or crossing instances through individual modeling, while neglecting the intrinsic interrelation between these conditions. In this work, we propose a Gradient Anomaly-aware Biomedical Instance Segmentation approach (GAInS), which leverages instance gradient information to perceive local gradient anomaly regions, thus modeling the spatial relationship between instances and refining local region segmentation. Specifically, GAInS is firstly built on a Gradient Anomaly Mapping Module (GAMM), which encodes the radial fields of instances through window sliding to obtain instance gradient anomaly maps. To efficiently refine boundaries and regions with gradient anomaly attention, we propose an Adaptive Local Refinement Module (ALRM) with a gradient anomaly-aware loss function. Extensive comparisons and ablation experiments in three biomedical scenarios demonstrate that our proposed GAInS outperforms other state-of-the-art (SOTA) instance segmentation methods. The code is available at https://github.com/DeepGAInS/GAInS.

Hao Jiang, Runsheng Liu, Yanning Zhou et al.

Cytology screening from Papanicolaou (Pap) smears is a common and effective tool for the preventive clinical management of cervical cancer, where abnormal cell detection from whole slide images serves as the foundation for reporting cervical cytology. However, cervical cell detection remains challenging due to 1) hazily-defined cell types (e.g., ASC-US) with subtle morphological discrepancies caused by the dynamic cancerization process, i.e., cell class ambiguity, and 2) imbalanced class distributions of clinical data may cause missed detection, especially for minor categories, i.e., cell class imbalance. To this end, we propose a holistic and historical instance comparison approach for cervical cell detection. Specifically, we first develop a holistic instance comparison scheme enforcing both RoI-level and class-level cell discrimination. This coarse-to-fine cell comparison encourages the model to learn foreground-distinguishable and class-wise representations. To emphatically improve the distinguishability of minor classes, we then introduce a historical instance comparison scheme with a confident sample selection-based memory bank, which involves comparing current embeddings with historical embeddings for better cell instance discrimination. Extensive experiments and analysis on two large-scale cytology datasets including 42,592 and 114,513 cervical cells demonstrate the effectiveness of our method. The code is available at https://github.com/hjiangaz/HERO.

Yingxue Xu, Yihui Wang, Fengtao Zhou et al.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Cheng Jin, Luyang Luo, Huangjing Lin et al.

Fine-grained classification of whole slide images (WSIs) is essential in precision oncology, enabling precise cancer diagnosis and personalized treatment strategies. The core of this task involves distinguishing subtle morphological variations within the same broad category of gigapixel-resolution images, which presents a significant challenge. While the multi-instance learning (MIL) paradigm alleviates the computational burden of WSIs, existing MIL methods often overlook hierarchical label correlations, treating fine-grained classification as a flat multi-class classification task. To overcome these limitations, we introduce a novel hierarchical multi-instance learning (HMIL) framework. By facilitating on the hierarchical alignment of inherent relationships between different hierarchy of labels at instance and bag level, our approach provides a more structured and informative learning process. Specifically, HMIL incorporates a class-wise attention mechanism that aligns hierarchical information at both the instance and bag levels. Furthermore, we introduce supervised contrastive learning to enhance the discriminative capability for fine-grained classification and a curriculum-based dynamic weighting module to adaptively balance the hierarchical feature during training. Extensive experiments on our large-scale cytology cervical cancer (CCC) dataset and two public histology datasets, BRACS and PANDA, demonstrate the state-of-the-art class-wise and overall performance of our HMIL framework. Our source code is available at https://github.com/ChengJin-git/HMIL.

Hao Jiang, Cheng Jin, Huangjing Lin et al.

Cervical cancer is a leading malignancy in female reproductive system. While AI-assisted cytology offers a cost-effective and non-invasive screening solution, current systems struggle with generalizability in complex clinical scenarios. To address this issue, we introduced Smart-CCS, a generalizable Cervical Cancer Screening paradigm based on pretraining and adaptation to create robust and generalizable screening systems. To develop and validate Smart-CCS, we first curated a large-scale, multi-center dataset named CCS-127K, which comprises a total of 127,471 cervical cytology whole-slide images collected from 48 medical centers. By leveraging large-scale self-supervised pretraining, our CCS models are equipped with strong generalization capability, potentially generalizing across diverse scenarios. Then, we incorporated test-time adaptation to specifically optimize the trained CCS model for complex clinical settings, which adapts and refines predictions, improving real-world applicability. We conducted large-scale system evaluation among various cohorts. In retrospective cohorts, Smart-CCS achieved an overall area under the curve (AUC) value of 0.965 and sensitivity of 0.913 for cancer screening on 11 internal test datasets. In external testing, system performance maintained high at 0.950 AUC across 6 independent test datasets. In prospective cohorts, our Smart-CCS achieved AUCs of 0.947, 0.924, and 0.986 in three prospective centers, respectively. Moreover, the system demonstrated superior sensitivity in diagnosing cervical cancer, confirming the accuracy of our cancer screening results by using histology findings for validation. Interpretability analysis with cell and slide predictions further indicated that the system's decision-making aligns with clinical practice. Smart-CCS represents a significant advancement in cancer screening across diverse clinical contexts.

Yanwen Li, Luyang Luo, Huangjing Lin et al.

Convolutional Neural Networks (CNNs) have shown remarkable progress in medical image segmentation. However, lesion segmentation remains a challenge to state-of-the-art CNN-based algorithms due to the variance in scales and shapes. On the one hand, tiny lesions are hard to be delineated precisely from the medical images which are often of low resolutions. On the other hand, segmenting large-size lesions requires large receptive fields, which exacerbates the first challenge. In this paper, we present a scale-aware super-resolution network to adaptively segment lesions of various sizes from the low-resolution medical images. Our proposed network contains dual branches to simultaneously conduct lesion mask super-resolution and lesion image super-resolution. The image super-resolution branch will provide more detailed features for the segmentation branch, i.e., the mask super-resolution branch, for fine-grained segmentation. Meanwhile, we introduce scale-aware dilated convolution blocks into the multi-task decoders to adaptively adjust the receptive fields of the convolutional kernels according to the lesion sizes. To guide the segmentation branch to learn from richer high-resolution features, we propose a feature affinity module and a scale affinity module to enhance the multi-task learning of the dual branches. On multiple challenging lesion segmentation datasets, our proposed network achieved consistent improvements compared to other state-of-the-art methods.

Luyang Luo, Hao Chen, Yongjie Xiao et al.

Two DL models were developed using radiograph-level annotations (yes or no disease) and fine-grained lesion-level annotations (lesion bounding boxes), respectively named CheXNet and CheXDet. The models' internal classification performance and lesion localization performance were compared on a testing set (n=2,922), external classification performance was compared on NIH-Google (n=4,376) and PadChest (n=24,536) datasets, and external lesion localization performance was compared on NIH-ChestX-ray14 dataset (n=880). The models were also compared to radiologists on a subset of the internal testing set (n=496). Given sufficient training data, both models performed comparably to radiologists. CheXDet achieved significant improvement for external classification, such as in classifying fracture on NIH-Google (CheXDet area under the ROC curve [AUC]: 0.67, CheXNet AUC: 0.51; p<.001) and PadChest (CheXDet AUC: 0.78, CheXNet AUC: 0.55; p<.001). CheXDet achieved higher lesion detection performance than CheXNet for most abnormalities on all datasets, such as in detecting pneumothorax on the internal set (CheXDet jacknife alternative free-response ROC-figure of merit [JAFROC-FOM]: 0.87, CheXNet JAFROC-FOM: 0.13; p<.001) and NIH-ChestX-ray14 (CheXDet JAFROC-FOM: 0.55, CheXNet JAFROC-FOM: 0.04; p<.001). To summarize, fine-grained annotations overcame shortcut learning and enabled DL models to identify correct lesion patterns, improving the models' generalizability.

Yanwen Li, Luyang Luo, Huangjing Lin et al.

The novel coronavirus disease 2019 (COVID-19) characterized by atypical pneumonia has caused millions of deaths worldwide. Automatically segmenting lesions from chest Computed Tomography (CT) is a promising way to assist doctors in COVID-19 screening, treatment planning, and follow-up monitoring. However, voxel-wise annotations are extremely expert-demanding and scarce, especially when it comes to novel diseases, while an abundance of unlabeled data could be available. To tackle the challenge of limited annotations, in this paper, we propose an uncertainty-guided dual-consistency learning network (UDC-Net) for semi-supervised COVID-19 lesion segmentation from CT images. Specifically, we present a dual-consistency learning scheme that simultaneously imposes image transformation equivalence and feature perturbation invariance to effectively harness the knowledge from unlabeled data. We then quantify the segmentation uncertainty in two forms and employ them together to guide the consistency regularization for more reliable unsupervised learning. Extensive experiments showed that our proposed UDC-Net improves the fully supervised method by 6.3% in Dice and outperforms other competitive semi-supervised approaches by significant margins, demonstrating high potential in real-world clinical practice.

Luyang Luo, Hao Chen, Yanning Zhou et al.

Chest X-ray (CXR) is the most typical diagnostic X-ray examination for screening various thoracic diseases. Automatically localizing lesions from CXR is promising for alleviating radiologists' reading burden. However, CXR datasets are often with massive 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. We first introduce supervised learning via a one-stage detection model. Then, we inject a global classification head to the detection model and propose dual attention alignment to guide the global gradient to the local detection branch, which enables learning lesion detection from image-level annotations. We also impose intra-class compactness and inter-class separability with global prototype alignment to further enhance the global information learning. Moreover, we leverage a soft focal loss to distill the soft pseudo-labels of unlabeled data generated by a teacher model. Extensive experiments on a large-scale chest X-ray dataset 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.

Shujun Wang, Yaxi Zhu, Lequan Yu et al.

The whole slide histopathology images (WSIs) play a critical role in gastric cancer diagnosis. However, due to the large scale of WSIs and various sizes of the abnormal area, how to select informative regions and analyze them are quite challenging during the automatic diagnosis process. The multi-instance learning based on the most discriminative instances can be of great benefit for whole slide gastric image diagnosis. In this paper, we design a recalibrated multi-instance deep learning method (RMDL) to address this challenging problem. We first select the discriminative instances, and then utilize these instances to diagnose diseases based on the proposed RMDL approach. The designed RMDL network is capable of capturing instance-wise dependencies and recalibrating instance features according to the importance coefficient learned from the fused features. Furthermore, we build a large whole-slide gastric histopathology image dataset with detailed pixel-level annotations. Experimental results on the constructed gastric dataset demonstrate the significant improvement on the accuracy of our proposed framework compared with other state-of-the-art multi-instance learning methods. Moreover, our method is general and can be extended to other diagnosis tasks of different cancer types based on WSIs.

Yanning Zhou, Hao Chen, Huangjing Lin et al.

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.

Zixu Zhao, Huangjing Lin, Hao Chen et al.

Automatic detection of cancer metastasis from whole slide images (WSIs) is a crucial step for following patient staging and prognosis. Recent convolutional neural network based approaches are struggling with the trade-off between accuracy and computational efficiency due to the difficulty in processing large-scale gigapixel WSIs. To meet this challenge, we propose a novel Pyramidal Feature Aggregation ScanNet (PFA-ScanNet) for robust and fast analysis of breast cancer metastasis. Our method mainly benefits from the aggregation of extracted local-to-global features with diverse receptive fields, as well as the proposed synergistic learning for training the main detector and extra decoder with semantic guidance. Furthermore, a high-efficiency inference mechanism is designed with dense pooling layers, which allows dense and fast scanning for gigapixel WSI analysis. As a result, the proposed PFA-ScanNet achieved the state-of-the-art FROC of 90.2% on the Camelyon16 dataset, as well as competitive kappa score of 0.905 on the Camelyon17 leaderboard. In addition, our method shows leading speed advantage over other methods, about 7.2 min per WSI with a single GPU, making automatic analysis of breast cancer metastasis more applicable in the clinical usage.

Qi Dou, Hao Chen, Yueming Jin et al.

In this paper, we propose a novel framework with 3D convolutional networks (ConvNets) for automated detection of pulmonary nodules from low-dose CT scans, which is a challenging yet crucial task for lung cancer early diagnosis and treatment. Different from previous standard ConvNets, we try to tackle the severe hard/easy sample imbalance problem in medical datasets and explore the benefits of localized annotations to regularize the learning, and hence boost the performance of ConvNets to achieve more accurate detections. Our proposed framework consists of two stages: 1) candidate screening, and 2) false positive reduction. In the first stage, we establish a 3D fully convolutional network, effectively trained with an online sample filtering scheme, to sensitively and rapidly screen the nodule candidates. In the second stage, we design a hybrid-loss residual network which harnesses the location and size information as important cues to guide the nodule recognition procedure. Experimental results on the public large-scale LUNA16 dataset demonstrate superior performance of our proposed method compared with state-of-the-art approaches for the pulmonary nodule detection task.

Huangjing Lin, Hao Chen, Qi Dou et al.

Lymph node metastasis is one of the most significant diagnostic indicators in breast cancer, which is traditionally observed under the microscope by pathologists. In recent years, computerized histology diagnosis has become one of the most rapidly expanding fields in medical image computing, which alleviates pathologists' workload and reduces misdiagnosis rate. However, automatic detection of lymph node metastases from whole slide images remains a challenging problem, due to the large-scale data with enormous resolutions and existence of hard mimics. In this paper, we propose a novel framework by leveraging fully convolutional networks for efficient inference to meet the speed requirement for clinical practice, while reconstructing dense predictions under different offsets for ensuring accurate detection on both micro- and macro-metastases. Incorporating with the strategies of asynchronous sample prefetching and hard negative mining, the network can be effectively trained. Extensive experiments on the benchmark dataset of 2016 Camelyon Grand Challenge corroborated the efficacy of our method. Compared with the state-of-the-art methods, our method achieved superior performance with a faster speed on the tumor localization task and surpassed human performance on the WSI classification task.