Zaiyi Liu

Yuhao Mo, Chu Han, Yu Liu et al. · pku

Ultrasonography is an important routine examination for breast cancer diagnosis, due to its non-invasive, radiation-free and low-cost properties. However, the diagnostic accuracy of breast cancer is still limited due to its inherent limitations. It would be a tremendous success if we can precisely diagnose breast cancer by breast ultrasound images (BUS). Many learning-based computer-aided diagnostic methods have been proposed to achieve breast cancer diagnosis/lesion classification. However, most of them require a pre-define ROI and then classify the lesion inside the ROI. Conventional classification backbones, such as VGG16 and ResNet50, can achieve promising classification results with no ROI requirement. But these models lack interpretability, thus restricting their use in clinical practice. In this study, we propose a novel ROI-free model for breast cancer diagnosis in ultrasound images with interpretable feature representations. We leverage the anatomical prior knowledge that malignant and benign tumors have different spatial relationships between different tissue layers, and propose a HoVer-Transformer to formulate this prior knowledge. The proposed HoVer-Trans block extracts the inter- and intra-layer spatial information horizontally and vertically. We conduct and release an open dataset GDPH&SYSUCC for breast cancer diagnosis in BUS. The proposed model is evaluated in three datasets by comparing with four CNN-based models and two vision transformer models via five-fold cross validation. It achieves state-of-the-art classification performance with the best model interpretability. In the meanwhile, our proposed model outperforms two senior sonographers on the breast cancer diagnosis when only one BUS image is given.

Heqin Zhu, Quan Quan, Qingsong Yao et al.

One-shot medical landmark detection gains much attention and achieves great success for its label-efficient training process. However, existing one-shot learning methods are highly specialized in a single domain and suffer domain preference heavily in the situation of multi-domain unlabeled data. Moreover, one-shot learning is not robust that it faces performance drop when annotating a sub-optimal image. To tackle these issues, we resort to developing a domain-adaptive one-shot landmark detection framework for handling multi-domain medical images, named Universal One-shot Detection (UOD). UOD consists of two stages and two corresponding universal models which are designed as combinations of domain-specific modules and domain-shared modules. In the first stage, a domain-adaptive convolution model is self-supervised learned to generate pseudo landmark labels. In the second stage, we design a domain-adaptive transformer to eliminate domain preference and build the global context for multi-domain data. Even though only one annotated sample from each domain is available for training, the domain-shared modules help UOD aggregate all one-shot samples to detect more robust and accurate landmarks. We investigated both qualitatively and quantitatively the proposed UOD on three widely-used public X-ray datasets in different anatomical domains (i.e., head, hand, chest) and obtained state-of-the-art performances in each domain. The code is available at https://github.com/heqin-zhu/UOD_universal_oneshot_detection.

Tianpeng Deng, Yanqi Huang, Guoqiang Han et al.

Histopathological tissue classification is a fundamental task in computational pathology. Deep learning-based models have achieved superior performance but centralized training with data centralization suffers from the privacy leakage problem. Federated learning (FL) can safeguard privacy by keeping training samples locally, but existing FL-based frameworks require a large number of well-annotated training samples and numerous rounds of communication which hinder their practicability in the real-world clinical scenario. In this paper, we propose a universal and lightweight federated learning framework, named Federated Deep-Broad Learning (FedDBL), to achieve superior classification performance with limited training samples and only one-round communication. By simply associating a pre-trained deep learning feature extractor, a fast and lightweight broad learning inference system and a classical federated aggregation approach, FedDBL can dramatically reduce data dependency and improve communication efficiency. Five-fold cross-validation demonstrates that FedDBL greatly outperforms the competitors with only one-round communication and limited training samples, while it even achieves comparable performance with the ones under multiple-round communications. Furthermore, due to the lightweight design and one-round communication, FedDBL reduces the communication burden from 4.6GB to only 276.5KB per client using the ResNet-50 backbone at 50-round training. Since no data or deep model sharing across different clients, the privacy issue is well-solved and the model security is guaranteed with no model inversion attack risk. Code is available at https://github.com/tianpeng-deng/FedDBL.

Wenao Ma, Cheng Chen, Jill Abrigo et al.

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Despite medical advances, predicting treat ment outcomes for ICH remains a challenge. This paper proposes a novel prognostic model that utilizes both imaging and tabular data to predict treatment outcome for ICH. Our model is trained on observational data collected from non-randomized controlled trials, providing reliable predictions of treatment success. Specifically, we propose to employ a variational autoencoder model to generate a low-dimensional prognostic score, which can effectively address the selection bias resulting from the non-randomized controlled trials. Importantly, we develop a variational distributions combination module that combines the information from imaging data, non-imaging clinical data, and treatment assignment to accurately generate the prognostic score. We conducted extensive experiments on a real-world clinical dataset of intracerebral hemorrhage. Our proposed method demonstrates a substantial improvement in treatment outcome prediction compared to existing state-of-the-art approaches. Code is available at https://github.com/med-air/TOP-GPM

Lingwei Meng, Di Dong, Xin Chen et al.

Objective: Radiomics, an emerging tool for medical image analysis, is potential towards precisely characterizing gastric cancer (GC). Whether using one-slice 2D annotation or whole-volume 3D annotation remains a long-time debate, especially for heterogeneous GC. We comprehensively compared 2D and 3D radiomic features' representation and discrimination capacity regarding GC, via three tasks. Methods: Four-center 539 GC patients were retrospectively enrolled and divided into the training and validation cohorts. From 2D or 3D regions of interest (ROIs) annotated by radiologists, radiomic features were extracted respectively. Feature selection and model construction procedures were customed for each combination of two modalities (2D or 3D) and three tasks. Subsequently, six machine learning models (Model_2D^LNM, Model_3D^LNM; Model_2D^LVI, Model_3D^LVI; Model_2D^pT, Model_3D^pT) were derived and evaluated to reflect modalities' performances in characterizing GC. Furthermore, we performed an auxiliary experiment to assess modalities' performances when resampling spacing is different. Results: Regarding three tasks, the yielded areas under the curve (AUCs) were: Model_2D^LNM's 0.712 (95% confidence interval, 0.613-0.811), Model_3D^LNM's 0.680 (0.584-0.775); Model_2D^LVI's 0.677 (0.595-0.761), Model_3D^LVI's 0.615 (0.528-0.703); Model_2D^pT's 0.840 (0.779-0.901), Model_3D^pT's 0.813 (0.747-0.879). Moreover, the auxiliary experiment indicated that Models_2D are statistically more advantageous than Models3D with different resampling spacings. Conclusion: Models constructed with 2D radiomic features revealed comparable performances with those constructed with 3D features in characterizing GC. Significance: Our work indicated that time-saving 2D annotation would be the better choice in GC, and provided a related reference to further radiomics-based researches.

Lei Zhou, Yuzhong Zhang, Jiadong Zhang et al.

Automated breast tumor segmentation on the basis of dynamic contrast-enhancement magnetic resonance imaging (DCE-MRI) has shown great promise in clinical practice, particularly for identifying the presence of breast disease. However, accurate segmentation of breast tumor is a challenging task, often necessitating the development of complex networks. To strike an optimal trade-off between computational costs and segmentation performance, we propose a hybrid network via the combination of convolution neural network (CNN) and transformer layers. Specifically, the hybrid network consists of a encoder-decoder architecture by stacking convolution and decovolution layers. Effective 3D transformer layers are then implemented after the encoder subnetworks, to capture global dependencies between the bottleneck features. To improve the efficiency of hybrid network, two parallel encoder subnetworks are designed for the decoder and the transformer layers, respectively. To further enhance the discriminative capability of hybrid network, a prototype learning guided prediction module is proposed, where the category-specified prototypical features are calculated through on-line clustering. All learned prototypical features are finally combined with the features from decoder for tumor mask prediction. The experimental results on private and public DCE-MRI datasets demonstrate that the proposed hybrid network achieves superior performance than the state-of-the-art (SOTA) methods, while maintaining balance between segmentation accuracy and computation cost. Moreover, we demonstrate that automatically generated tumor masks can be effectively applied to identify HER2-positive subtype from HER2-negative subtype with the similar accuracy to the analysis based on manual tumor segmentation. The source code is available at https://github.com/ZhouL-lab/PLHN.

Jianwei Lin, Jiatai Lin, Cheng Lu et al.

Brain tumor segmentation (BTS) in magnetic resonance image (MRI) is crucial for brain tumor diagnosis, cancer management and research purposes. With the great success of the ten-year BraTS challenges as well as the advances of CNN and Transformer algorithms, a lot of outstanding BTS models have been proposed to tackle the difficulties of BTS in different technical aspects. However, existing studies hardly consider how to fuse the multi-modality images in a reasonable manner. In this paper, we leverage the clinical knowledge of how radiologists diagnose brain tumors from multiple MRI modalities and propose a clinical knowledge-driven brain tumor segmentation model, called CKD-TransBTS. Instead of directly concatenating all the modalities, we re-organize the input modalities by separating them into two groups according to the imaging principle of MRI. A dual-branch hybrid encoder with the proposed modality-correlated cross-attention block (MCCA) is designed to extract the multi-modality image features. The proposed model inherits the strengths from both Transformer and CNN with the local feature representation ability for precise lesion boundaries and long-range feature extraction for 3D volumetric images. To bridge the gap between Transformer and CNN features, we propose a Trans&CNN Feature Calibration block (TCFC) in the decoder. We compare the proposed model with five CNN-based models and six transformer-based models on the BraTS 2021 challenge dataset. Extensive experiments demonstrate that the proposed model achieves state-of-the-art brain tumor segmentation performance compared with all the competitors.

Jieneng Chen, Yingda Xia, Jiawen Yao et al.

Human readers or radiologists routinely perform full-body multi-organ multi-disease detection and diagnosis in clinical practice, while most medical AI systems are built to focus on single organs with a narrow list of a few diseases. This might severely limit AI's clinical adoption. A certain number of AI models need to be assembled non-trivially to match the diagnostic process of a human reading a CT scan. In this paper, we construct a Unified Tumor Transformer (CancerUniT) model to jointly detect tumor existence & location and diagnose tumor characteristics for eight major cancers in CT scans. CancerUniT is a query-based Mask Transformer model with the output of multi-tumor prediction. We decouple the object queries into organ queries, tumor detection queries and tumor diagnosis queries, and further establish hierarchical relationships among the three groups. This clinically-inspired architecture effectively assists inter- and intra-organ representation learning of tumors and facilitates the resolution of these complex, anatomically related multi-organ cancer image reading tasks. CancerUniT is trained end-to-end using a curated large-scale CT images of 10,042 patients including eight major types of cancers and occurring non-cancer tumors (all are pathology-confirmed with 3D tumor masks annotated by radiologists). On the test set of 631 patients, CancerUniT has demonstrated strong performance under a set of clinically relevant evaluation metrics, substantially outperforming both multi-disease methods and an assembly of eight single-organ expert models in tumor detection, segmentation, and diagnosis. This moves one step closer towards a universal high performance cancer screening tool.

Hao Wang, Jiatai Lin, Danyi Li et al.

Mitosis detection is one of the fundamental tasks in computational pathology, which is extremely challenging due to the heterogeneity of mitotic cell. Most of the current studies solve the heterogeneity in the technical aspect by increasing the model complexity. However, lacking consideration of the biological knowledge and the complex model design may lead to the overfitting problem while limited the generalizability of the detection model. In this paper, we systematically study the morphological appearances in different mitotic phases as well as the ambiguous non-mitotic cells and identify that balancing the data and feature diversity can achieve better generalizability. Based on this observation, we propose a novel generalizable framework (MitDet) for mitosis detection. The data diversity is considered by the proposed diversity-guided sample balancing (DGSB). And the feature diversity is preserved by inter- and intra- class feature diversity-preserved module (InCDP). Stain enhancement (SE) module is introduced to enhance the domain-relevant diversity of both data and features simultaneously. Extensive experiments have demonstrated that our proposed model outperforms all the SOTA approaches in several popular mitosis detection datasets in both internal and external test sets using minimal annotation efforts with point annotations only. Comprehensive ablation studies have also proven the effectiveness of the rethinking of data and feature diversity balancing. By analyzing the results quantitatively and qualitatively, we believe that our proposed model not only achieves SOTA performance but also might inspire the future studies in new perspectives. Source code is at https://github.com/Onehour0108/MitDet.

Simon Graham, Quoc Dang Vu, Mostafa Jahanifar et al.

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

Chu Han, Xipeng Pan, Lixu Yan et al.

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma (LUAD) is the most common subtype. Exploiting the potential value of the histopathology images can promote precision medicine in oncology. Tissue segmentation is the basic upstream task of histopathology image analysis. Existing deep learning models have achieved superior segmentation performance but require sufficient pixel-level annotations, which is time-consuming and expensive. To enrich the label resources of LUAD and to alleviate the annotation efforts, we organize this challenge WSSS4LUAD to call for the outstanding weakly-supervised semantic segmentation (WSSS) techniques for histopathology images of LUAD. Participants have to design the algorithm to segment tumor epithelial, tumor-associated stroma and normal tissue with only patch-level labels. This challenge includes 10,091 patch-level annotations (the training set) and over 130 million labeled pixels (the validation and test sets), from 87 WSIs (67 from GDPH, 20 from TCGA). All the labels were generated by a pathologist-in-the-loop pipeline with the help of AI models and checked by the label review board. Among 532 registrations, 28 teams submitted the results in the test phase with over 1,000 submissions. Finally, the first place team achieved mIoU of 0.8413 (tumor: 0.8389, stroma: 0.7931, normal: 0.8919). According to the technical reports of the top-tier teams, CAM is still the most popular approach in WSSS. Cutmix data augmentation has been widely adopted to generate more reliable samples. With the success of this challenge, we believe that WSSS approaches with patch-level annotations can be a complement to the traditional pixel annotations while reducing the annotation efforts. The entire dataset has been released to encourage more researches on computational pathology in LUAD and more novel WSSS techniques.

Mingze Yuan, Yingda Xia, Hexin Dong et al.

Real-world medical image segmentation has tremendous long-tailed complexity of objects, among which tail conditions correlate with relatively rare diseases and are clinically significant. A trustworthy medical AI algorithm should demonstrate its effectiveness on tail conditions to avoid clinically dangerous damage in these out-of-distribution (OOD) cases. In this paper, we adopt the concept of object queries in Mask Transformers to formulate semantic segmentation as a soft cluster assignment. The queries fit the feature-level cluster centers of inliers during training. Therefore, when performing inference on a medical image in real-world scenarios, the similarity between pixels and the queries detects and localizes OOD regions. We term this OOD localization as MaxQuery. Furthermore, the foregrounds of real-world medical images, whether OOD objects or inliers, are lesions. The difference between them is less than that between the foreground and background, possibly misleading the object queries to focus redundantly on the background. Thus, we propose a query-distribution (QD) loss to enforce clear boundaries between segmentation targets and other regions at the query level, improving the inlier segmentation and OOD indication. Our proposed framework is tested on two real-world segmentation tasks, i.e., segmentation of pancreatic and liver tumors, outperforming previous state-of-the-art algorithms by an average of 7.39% on AUROC, 14.69% on AUPR, and 13.79% on FPR95 for OOD localization. On the other hand, our framework improves the performance of inlier segmentation by an average of 5.27% DSC when compared with the leading baseline nnUNet.

Fenghe Tang, Ronghao Xu, Qingsong Yao et al.

The generative self-supervised learning strategy exhibits remarkable learning representational capabilities. However, there is limited attention to end-to-end pre-training methods based on a hybrid architecture of CNN and Transformer, which can learn strong local and global representations simultaneously. To address this issue, we propose a generative pre-training strategy called Hybrid Sparse masKing (HySparK) based on masked image modeling and apply it to large-scale pre-training on medical images. First, we perform a bottom-up 3D hybrid masking strategy on the encoder to keep consistency masking. Then we utilize sparse convolution for the top CNNs and encode unmasked patches for the bottom vision Transformers. Second, we employ a simple hierarchical decoder with skip-connections to achieve dense multi-scale feature reconstruction. Third, we implement our pre-training method on a collection of multiple large-scale 3D medical imaging datasets. Extensive experiments indicate that our proposed pre-training strategy demonstrates robust transfer-ability in supervised downstream tasks and sheds light on HySparK's promising prospects. The code is available at https://github.com/FengheTan9/HySparK

Hexin Dong, Jiawen Yao, Yuxing Tang et al.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer in which the tumor-vascular involvement greatly affects the resectability and, thus, overall survival of patients. However, current prognostic prediction methods fail to explicitly and accurately investigate relationships between the tumor and nearby important vessels. This paper proposes a novel learnable neural distance that describes the precise relationship between the tumor and vessels in CT images of different patients, adopting it as a major feature for prognosis prediction. Besides, different from existing models that used CNNs or LSTMs to exploit tumor enhancement patterns on dynamic contrast-enhanced CT imaging, we improved the extraction of dynamic tumor-related texture features in multi-phase contrast-enhanced CT by fusing local and global features using CNN and transformer modules, further enhancing the features extracted across multi-phase CT images. We extensively evaluated and compared the proposed method with existing methods in the multi-center (n=4) dataset with 1,070 patients with PDAC, and statistical analysis confirmed its clinical effectiveness in the external test set consisting of three centers. The developed risk marker was the strongest predictor of overall survival among preoperative factors and it has the potential to be combined with established clinical factors to select patients at higher risk who might benefit from neoadjuvant therapy.

Jianpeng Zhang, Xianghua Ye, Jianfeng Zhang et al.

Lung cancer is a leading cause of death worldwide and early screening is critical for improving survival outcomes. In clinical practice, the contextual structure of nodules and the accumulated experience of radiologists are the two core elements related to the accuracy of identification of benign and malignant nodules. Contextual information provides comprehensive information about nodules such as location, shape, and peripheral vessels, and experienced radiologists can search for clues from previous cases as a reference to enrich the basis of decision-making. In this paper, we propose a radiologist-inspired method to simulate the diagnostic process of radiologists, which is composed of context parsing and prototype recalling modules. The context parsing module first segments the context structure of nodules and then aggregates contextual information for a more comprehensive understanding of the nodule. The prototype recalling module utilizes prototype-based learning to condense previously learned cases as prototypes for comparative analysis, which is updated online in a momentum way during training. Building on the two modules, our method leverages both the intrinsic characteristics of the nodules and the external knowledge accumulated from other nodules to achieve a sound diagnosis. To meet the needs of both low-dose and noncontrast screening, we collect a large-scale dataset of 12,852 and 4,029 nodules from low-dose and noncontrast CTs respectively, each with pathology- or follow-up-confirmed labels. Experiments on several datasets demonstrate that our method achieves advanced screening performance on both low-dose and noncontrast scenarios.

Mingze Yuan, Yingda Xia, Xin Chen et al.

Gastric cancer is the third leading cause of cancer-related mortality worldwide, but no guideline-recommended screening test exists. Existing methods can be invasive, expensive, and lack sensitivity to identify early-stage gastric cancer. In this study, we explore the feasibility of using a deep learning approach on non-contrast CT scans for gastric cancer detection. We propose a novel cluster-induced Mask Transformer that jointly segments the tumor and classifies abnormality in a multi-task manner. Our model incorporates learnable clusters that encode the texture and shape prototypes of gastric cancer, utilizing self- and cross-attention to interact with convolutional features. In our experiments, the proposed method achieves a sensitivity of 85.0% and specificity of 92.6% for detecting gastric tumors on a hold-out test set consisting of 100 patients with cancer and 148 normal. In comparison, two radiologists have an average sensitivity of 73.5% and specificity of 84.3%. We also obtain a specificity of 97.7% on an external test set with 903 normal cases. Our approach performs comparably to established state-of-the-art gastric cancer screening tools like blood testing and endoscopy, while also being more sensitive in detecting early-stage cancer. This demonstrates the potential of our approach as a novel, non-invasive, low-cost, and accurate method for opportunistic gastric cancer screening.

Jijun Cheng, Xipeng Pan, Feihu Hou et al.

Nuclear segmentation and classification is an essential step for computational pathology. TIA lab from Warwick University organized a nuclear segmentation and classification challenge (CoNIC) for H&E stained histopathology images in colorectal cancer with two highly correlated tasks, nuclei segmentation and classification task and cellular composition task. There are a few obstacles we have to address in this challenge, 1) limited training samples, 2) color variation, 3) imbalanced annotations, 4) similar morphological appearance among classes. To deal with these challenges, we proposed a standardized pipeline for nuclear segmentation and classification by integrating several pluggable components. First, we built a GAN-based model to automatically generate pseudo images for data augmentation. Then we trained a self-supervised stain normalization model to solve the color variation problem. Next we constructed a baseline model HoVer-Net with cost-sensitive loss to encourage the model pay more attention on the minority classes. According to the results of the leaderboard, our proposed pipeline achieves 0.40665 mPQ+ (Rank 49th) and 0.62199 r2 (Rank 10th) in the preliminary test phase.

Jiatai Lin, Guoqiang Han, Xuemiao Xu et al.

Class activation mapping~(CAM), a visualization technique for interpreting deep learning models, is now commonly used for weakly supervised semantic segmentation~(WSSS) and object localization~(WSOL). It is the weighted aggregation of the feature maps by activating the high class-relevance ones. Current CAM methods achieve it relying on the training outcomes, such as predicted scores~(forward information), gradients~(backward information), etc. However, when with small-scale data, unstable training may lead to less effective model outcomes and generate unreliable weights, finally resulting in incorrect activation and noisy CAM seeds. In this paper, we propose an outcome-agnostic CAM approach, called BroadCAM, for small-scale weakly supervised applications. Since broad learning system (BLS) is independent to the model learning, BroadCAM can avoid the weights being affected by the unreliable model outcomes when with small-scale data. By evaluating BroadCAM on VOC2012 (natural images) and BCSS-WSSS (medical images) for WSSS and OpenImages30k for WSOL, BroadCAM demonstrates superior performance than existing CAM methods with small-scale data (less than 5\%) in different CNN architectures. It also achieves SOTA performance with large-scale training data. Extensive qualitative comparisons are conducted to demonstrate how BroadCAM activates the high class-relevance feature maps and generates reliable CAMs when with small-scale training data.

Zheren Li, Zhiming Cui, Lichi Zhang et al.

The deep learning technique has been shown to be effectively addressed several image analysis tasks in the computer-aided diagnosis scheme for mammography. The training of an efficacious deep learning model requires large data with diverse styles and qualities. The diversity of data often comes from the use of various scanners of vendors. But, in practice, it is impractical to collect a sufficient amount of diverse data for training. To this end, a novel contrastive learning is developed to equip the deep learning models with better style generalization capability. Specifically, the multi-style and multi-view unsupervised self-learning scheme is carried out to seek robust feature embedding against style diversity as a pretrained model. Afterward, the pretrained network is further fine-tuned to the downstream tasks, e.g., mass detection, matching, BI-RADS rating, and breast density classification. The proposed method has been evaluated extensively and rigorously with mammograms from various vendor style domains and several public datasets. The experimental results suggest that the proposed domain generalization method can effectively improve performance of four mammographic image tasks on the data from both seen and unseen domains, and outperform many state-of-the-art (SOTA) generalization methods.

Xiaojing Guo, Jiatai Lin, Yumian Jia et al.

Generalist pathology foundation models (PFMs), pretrained on large-scale multi-organ datasets, have demonstrated remarkable predictive capabilities across diverse clinical applications. However, their proficiency on the full spectrum of clinically essential tasks within a specific organ system remains an open question due to the lack of large-scale validation cohorts for a single organ as well as the absence of a tailored training paradigm that can effectively translate broad histomorphological knowledge into the organ-specific expertise required for specialist-level interpretation. In this study, we propose BRIGHT, the first PFM specifically designed for breast pathology, trained on approximately 210 million histopathology tiles from over 51,000 breast whole-slide images derived from a cohort of over 40,000 patients across 19 hospitals. BRIGHT employs a collaborative generalist-specialist framework to capture both universal and organ-specific features. To comprehensively evaluate the performance of PFMs on breast oncology, we curate the largest multi-institutional cohorts to date for downstream task development and evaluation, comprising over 25,000 WSIs across 10 hospitals. The validation cohorts cover the full spectrum of breast pathology across 24 distinct clinical tasks spanning diagnosis, biomarker prediction, treatment response and survival prediction. Extensive experiments demonstrate that BRIGHT outperforms three leading generalist PFMs, achieving state-of-the-art (SOTA) performance in 21 of 24 internal validation tasks and in 5 of 10 external validation tasks with excellent heatmap interpretability. By evaluating on large-scale validation cohorts, this study not only demonstrates BRIGHT's clinical utility in breast oncology but also validates a collaborative generalist-specialist paradigm, providing a scalable template for developing PFMs on a specific organ system.

Jiahua Xu, Dawei Zhou, Lei Hu et al.

Motion artifacts present in magnetic resonance imaging (MRI) can seriously interfere with clinical diagnosis. Removing motion artifacts is a straightforward solution and has been extensively studied. However, paired data are still heavily relied on in recent works and the perturbations in k-space (frequency domain) are not well considered, which limits their applications in the clinical field. To address these issues, we propose a novel unsupervised purification method which leverages pixel-frequency information of noisy MRI images to guide a pre-trained diffusion model to recover clean MRI images. Specifically, considering that motion artifacts are mainly concentrated in high-frequency components in k-space, we utilize the low-frequency components as the guide to ensure correct tissue textures. Additionally, given that high-frequency and pixel information are helpful for recovering shape and detail textures, we design alternate complementary masks to simultaneously destroy the artifact structure and exploit useful information. Quantitative experiments are performed on datasets from different tissues and show that our method achieves superior performance on several metrics. Qualitative evaluations with radiologists also show that our method provides better clinical feedback. Our code is available at https://github.com/medcx/PFAD.

Chu Han, Jiatai Lin, Jinhai Mai et al.

Tissue-level semantic segmentation is a vital step in computational pathology. Fully-supervised models have already achieved outstanding performance with dense pixel-level annotations. However, drawing such labels on the giga-pixel whole slide images is extremely expensive and time-consuming. In this paper, we use only patch-level classification labels to achieve tissue semantic segmentation on histopathology images, finally reducing the annotation efforts. We proposed a two-step model including a classification and a segmentation phases. In the classification phase, we proposed a CAM-based model to generate pseudo masks by patch-level labels. In the segmentation phase, we achieved tissue semantic segmentation by our proposed Multi-Layer Pseudo-Supervision. Several technical novelties have been proposed to reduce the information gap between pixel-level and patch-level annotations. As a part of this paper, we introduced a new weakly-supervised semantic segmentation (WSSS) dataset for lung adenocarcinoma (LUAD-HistoSeg). We conducted several experiments to evaluate our proposed model on two datasets. Our proposed model outperforms two state-of-the-art WSSS approaches. Note that we can achieve comparable quantitative and qualitative results with the fully-supervised model, with only around a 2\% gap for MIoU and FwIoU. By comparing with manual labeling, our model can greatly save the annotation time from hours to minutes. The source code is available at: \url{https://github.com/ChuHan89/WSSS-Tissue}.

Shanshan Wang, Cheng Li, Rongpin Wang et al.

Automatic medical image segmentation plays a critical role in scientific research and medical care. Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, we introduce Annotation-effIcient Deep lEarning (AIDE), an open-source framework to handle imperfect training datasets. Methodological analyses and empirical evaluations are conducted, and we demonstrate that AIDE surpasses conventional fully-supervised models by presenting better performance on open datasets possessing scarce or noisy annotations. We further test AIDE in a real-life case study for breast tumor segmentation. Three datasets containing 11,852 breast images from three medical centers are employed, and AIDE, utilizing 10% training annotations, consistently produces segmentation maps comparable to those generated by fully-supervised counterparts or provided by independent radiologists. The 10-fold enhanced efficiency in utilizing expert labels has the potential to promote a wide range of biomedical applications.

Kehan Qi, Hao Yang, Cheng Li et al.

The morbidity of brain stroke increased rapidly in the past few years. To help specialists in lesion measurements and treatment planning, automatic segmentation methods are critically required for clinical practices. Recently, approaches based on deep learning and methods for contextual information extraction have served in many image segmentation tasks. However, their performances are limited due to the insufficient training of a large number of parameters, which sometimes fail in capturing long-range dependencies. To address these issues, we propose a depthwise separable convolution based X-Net that designs a nonlocal operation namely Feature Similarity Module (FSM) to capture long-range dependencies. The adopted depthwise convolution allows to reduce the network size, while the developed FSM provides a more effective, dense contextual information extraction and thus facilitates better segmentation. The effectiveness of X-Net was evaluated on an open dataset Anatomical Tracings of Lesions After Stroke (ATLAS) with superior performance achieved compared to other six state-of-the-art approaches. We make our code and models available at https://github.com/Andrewsher/X-Net.

Wei Fang, Yuxing Tang, Heng Guo et al.

In the realm of medical 3D data, such as CT and MRI images, prevalent anisotropic resolution is characterized by high intra-slice but diminished inter-slice resolution. The lowered resolution between adjacent slices poses challenges, hindering optimal viewing experiences and impeding the development of robust downstream analysis algorithms. Various volumetric super-resolution algorithms aim to surmount these challenges, enhancing inter-slice resolution and overall 3D medical imaging quality. However, existing approaches confront inherent challenges: 1) often tailored to specific upsampling factors, lacking flexibility for diverse clinical scenarios; 2) newly generated slices frequently suffer from over-smoothing, degrading fine details, and leading to inter-slice inconsistency. In response, this study presents CycleINR, a novel enhanced Implicit Neural Representation model for 3D medical data volumetric super-resolution. Leveraging the continuity of the learned implicit function, the CycleINR model can achieve results with arbitrary up-sampling rates, eliminating the need for separate training. Additionally, we enhance the grid sampling in CycleINR with a local attention mechanism and mitigate over-smoothing by integrating cycle-consistent loss. We introduce a new metric, Slice-wise Noise Level Inconsistency (SNLI), to quantitatively assess inter-slice noise level inconsistency. The effectiveness of our approach is demonstrated through image quality evaluations on an in-house dataset and a downstream task analysis on the Medical Segmentation Decathlon liver tumor dataset.

Quan Liu, Jiawen Yao, Lisha Yao et al.

Colorectal cancer (CRC) micro-satellite instability (MSI) prediction on histopathology images is a challenging weakly supervised learning task that involves multi-instance learning on gigapixel images. To date, radiology images have proven to have CRC MSI information and efficient patient imaging techniques. Different data modalities integration offers the opportunity to increase the accuracy and robustness of MSI prediction. Despite the progress in representation learning from the whole slide images (WSI) and exploring the potential of making use of radiology data, CRC MSI prediction remains a challenge to fuse the information from multiple data modalities (e.g., pathology WSI and radiology CT image). In this paper, we propose $M^{2}$Fusion: a Bayesian-based multimodal multi-level fusion pipeline for CRC MSI. The proposed fusion model $M^{2}$Fusion is capable of discovering more novel patterns within and across modalities that are beneficial for predicting MSI than using a single modality alone, as well as other fusion methods. The contribution of the paper is three-fold: (1) $M^{2}$Fusion is the first pipeline of multi-level fusion on pathology WSI and 3D radiology CT image for MSI prediction; (2) CT images are the first time integrated into multimodal fusion for CRC MSI prediction; (3) feature-level fusion strategy is evaluated on both Transformer-based and CNN-based method. Our approach is validated on cross-validation of 352 cases and outperforms either feature-level (0.8177 vs. 0.7908) or decision-level fusion strategy (0.8177 vs. 0.7289) on AUC score.

Jiahua Xu, Dawei Zhou, Lei Hu et al.

Multimodal medical images play a crucial role in the precise and comprehensive clinical diagnosis. Diffusion model is a powerful strategy to synthesize the required medical images. However, existing approaches still suffer from the problem of anatomical structure distortion due to the overfitting of high-frequency information and the weakening of low-frequency information. Thus, we propose a novel method based on dynamic frequency balance and knowledge guidance. Specifically, we first extract the low-frequency and high-frequency components by decomposing the critical features of the model using wavelet transform. Then, a dynamic frequency balance module is designed to adaptively adjust frequency for enhancing global low-frequency features and effective high-frequency details as well as suppressing high-frequency noise. To further overcome the challenges posed by the large differences between different medical modalities, we construct a knowledge-guided mechanism that fuses the prior clinical knowledge from a visual language model with visual features, to facilitate the generation of accurate anatomical structures. Experimental evaluations on multiple datasets show the proposed method achieves significant improvements in qualitative and quantitative assessments, verifying its effectiveness and superiority.

Chu Han, Bingchao Zhao, Jiatai Lin et al.

Despite the impressive performance across a wide range of applications, current computational pathology models face significant diagnostic efficiency challenges due to their reliance on high-magnification whole-slide image analysis. This limitation severely compromises their clinical utility, especially in time-sensitive diagnostic scenarios and situations requiring efficient data transfer. To address these issues, we present a novel computation- and communication-efficient framework called Magnification-Aligned Global-Local Transformer (MAG-GLTrans). Our approach significantly reduces computational time, file transfer requirements, and storage overhead by enabling effective analysis using low-magnification inputs rather than high-magnification ones. The key innovation lies in our proposed magnification alignment (MAG) mechanism, which employs self-supervised learning to bridge the information gap between low and high magnification levels by effectively aligning their feature representations. Through extensive evaluation across various fundamental CPath tasks, MAG-GLTrans demonstrates state-of-the-art classification performance while achieving remarkable efficiency gains: up to 10.7 times reduction in computational time and over 20 times reduction in file transfer and storage requirements. Furthermore, we highlight the versatility of our MAG framework through two significant extensions: (1) its applicability as a feature extractor to enhance the efficiency of any CPath architecture, and (2) its compatibility with existing foundation models and histopathology-specific encoders, enabling them to process low-magnification inputs with minimal information loss. These advancements position MAG-GLTrans as a particularly promising solution for time-sensitive applications, especially in the context of intraoperative frozen section diagnosis where both accuracy and efficiency are paramount.

Bingchao Zhao, Jiatai Lin, Changhong Liang et al.

Color inconsistency is an inevitable challenge in computational pathology, which generally happens because of stain intensity variations or sections scanned by different scanners. It harms the pathological image analysis methods, especially the learning-based models. A series of approaches have been proposed for stain normalization. However, most of them are lack flexibility in practice. In this paper, we formulated stain normalization as a digital re-staining process and proposed a self-supervised learning model, which is called RestainNet. Our network is regarded as a digital restainer which learns how to re-stain an unstained (grayscale) image. Two digital stains, Hematoxylin (H) and Eosin (E) were extracted from the original image by Beer-Lambert's Law. We proposed a staining loss to maintain the correctness of stain intensity during the restaining process. Thanks to the self-supervised nature, paired training samples are no longer necessary, which demonstrates great flexibility in practical usage. Our RestainNet outperforms existing approaches and achieves state-of-the-art performance with regard to color correctness and structure preservation. We further conducted experiments on the segmentation and classification tasks and the proposed RestainNet achieved outstanding performance compared with SOTA methods. The self-supervised design allows the network to learn any staining style with no extra effort.

Longfei Li, Rui Yang, Xin Chen et al.

Prostate Imaging Reporting and Data System (PI-RADS) based on multi-parametric MRI classiêes patients into 5 categories (PI-RADS 1-5) for routine clinical diagnosis guidance. However, there is no consensus on whether PI-RADS 3 patients should go through biopsies. Mining features from these hard samples (HS) is meaningful for physicians to achieve accurate diagnoses. Currently, the mining of HS biomarkers is insuìcient, and the eéectiveness and robustness of HS biomarkers for prostate cancer diagnosis have not been explored. In this study, biomarkers from diéerent data distributions are constructed. Results show that HS biomarkers can achieve better performances in diéerent data distributions.

Jiatai Lin, Guoqiang Han, Xipeng Pan et al.

Histopathological tissue classification is a fundamental task in pathomics cancer research. Precisely differentiating different tissue types is a benefit for the downstream researches, like cancer diagnosis, prognosis and etc. Existing works mostly leverage the popular classification backbones in computer vision to achieve histopathological tissue classification. In this paper, we proposed a super lightweight plug-and-play module, named Pyramidal Deep-Broad Learning (PDBL), for any well-trained classification backbone to further improve the classification performance without a re-training burden. We mimic how pathologists observe pathology slides in different magnifications and construct an image pyramid for the input image in order to obtain the pyramidal contextual information. For each level in the pyramid, we extract the multi-scale deep-broad features by our proposed Deep-Broad block (DB-block). We equipped PDBL in three popular classification backbones, ShuffLeNetV2, EfficientNetb0, and ResNet50 to evaluate the effectiveness and efficiency of our proposed module on two datasets (Kather Multiclass Dataset and the LC25000 Dataset). Experimental results demonstrate the proposed PDBL can steadily improve the tissue-level classification performance for any CNN backbones, especially for the lightweight models when given a small among of training samples (less than 10%), which greatly saves the computational time and annotation efforts.

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.

Cheng Li, Hui Sun, Zaiyi Liu et al.

Multi-modal magnetic resonance imaging (MRI) is essential in clinics for comprehensive diagnosis and surgical planning. Nevertheless, the segmentation of multi-modal MR images tends to be time-consuming and challenging. Convolutional neural network (CNN)-based multi-modal MR image analysis commonly proceeds with multiple down-sampling streams fused at one or several layers. Although inspiring performance has been achieved, the feature fusion is usually conducted through simple summation or concatenation without optimization. In this work, we propose a supervised image fusion method to selectively fuse the useful information from different modalities and suppress the respective noise signals. Specifically, an attention block is introduced as guidance for the information selection. From the different modalities, one modality that contributes most to the results is selected as the master modality, which supervises the information selection of the other assistant modalities. The effectiveness of the proposed method is confirmed through breast mass segmentation in MR images of two modalities and better segmentation results are achieved compared to the state-of-the-art methods.