Linhao Qu

Linhao Qu, Xiaoyuan Luo, Manning Wang et al.

Computer-aided pathology diagnosis based on the classification of Whole Slide Image (WSI) plays an important role in clinical practice, and it is often formulated as a weakly-supervised Multiple Instance Learning (MIL) problem. Existing methods solve this problem from either a bag classification or an instance classification perspective. In this paper, we propose an end-to-end weakly supervised knowledge distillation framework (WENO) for WSI classification, which integrates a bag classifier and an instance classifier in a knowledge distillation framework to mutually improve the performance of both classifiers. Specifically, an attention-based bag classifier is used as the teacher network, which is trained with weak bag labels, and an instance classifier is used as the student network, which is trained using the normalized attention scores obtained from the teacher network as soft pseudo labels for the instances in positive bags. An instance feature extractor is shared between the teacher and the student to further enhance the knowledge exchange between them. In addition, we propose a hard positive instance mining strategy based on the output of the student network to force the teacher network to keep mining hard positive instances. WENO is a plug-and-play framework that can be easily applied to any existing attention-based bag classification methods. Extensive experiments on five datasets demonstrate the efficiency of WENO. Code is available at https://github.com/miccaiif/WENO.

Linhao Qu, Yingfan Ma, Xiaoyuan Luo et al.

Weakly supervised whole slide image classification is usually formulated as a multiple instance learning (MIL) problem, where each slide is treated as a bag, and the patches cut out of it are treated as instances. Existing methods either train an instance classifier through pseudo-labeling or aggregate instance features into a bag feature through attention mechanisms and then train a bag classifier, where the attention scores can be used for instance-level classification. However, the pseudo instance labels constructed by the former usually contain a lot of noise, and the attention scores constructed by the latter are not accurate enough, both of which affect their performance. In this paper, we propose an instance-level MIL framework based on contrastive learning and prototype learning to effectively accomplish both instance classification and bag classification tasks. To this end, we propose an instance-level weakly supervised contrastive learning algorithm for the first time under the MIL setting to effectively learn instance feature representation. We also propose an accurate pseudo label generation method through prototype learning. We then develop a joint training strategy for weakly supervised contrastive learning, prototype learning, and instance classifier training. Extensive experiments and visualizations on four datasets demonstrate the powerful performance of our method. Codes are available at https://github.com/miccaiif/INS.

Minghao Han, Linhao Qu, Dingkang Yang et al.

Multiple instance learning (MIL) has become a standard paradigm for the weakly supervised classification of whole slide images (WSIs). However, this paradigm relies on using a large number of labeled WSIs for training. The lack of training data and the presence of rare diseases pose significant challenges for these methods. Prompt tuning combined with pre-trained Vision-Language models (VLMs) is an effective solution to the Few-shot Weakly Supervised WSI Classification (FSWC) task. Nevertheless, applying prompt tuning methods designed for natural images to WSIs presents three significant challenges: 1) These methods fail to fully leverage the prior knowledge from the VLM's text modality; 2) They overlook the essential multi-scale and contextual information in WSIs, leading to suboptimal results; and 3) They lack exploration of instance aggregation methods. To address these problems, we propose a Multi-Scale and Context-focused Prompt Tuning (MSCPT) method for FSWC task. Specifically, MSCPT employs the frozen large language model to generate pathological visual language prior knowledge at multiple scales, guiding hierarchical prompt tuning. Additionally, we design a graph prompt tuning module to learn essential contextual information within WSI, and finally, a non-parametric cross-guided instance aggregation module has been introduced to derive the WSI-level features. Extensive experiments, visualizations, and interpretability analyses were conducted on five datasets and three downstream tasks using three VLMs, demonstrating the strong performance of our MSCPT. All codes have been made publicly accessible at https://github.com/Hanminghao/MSCPT.

Linhao Qu, Yingfan Ma, Zhiwei Yang et al.

Active learning (AL) is an effective approach to select the most informative samples to label so as to reduce the annotation cost. Existing AL methods typically work under the closed-set assumption, i.e., all classes existing in the unlabeled sample pool need to be classified by the target model. However, in some practical clinical tasks, the unlabeled pool may contain not only the target classes that need to be fine-grainedly classified, but also non-target classes that are irrelevant to the clinical tasks. Existing AL methods cannot work well in this scenario because they tend to select a large number of non-target samples. In this paper, we formulate this scenario as an open-set AL problem and propose an efficient framework, OpenAL, to address the challenge of querying samples from an unlabeled pool with both target class and non-target class samples. Experiments on fine-grained classification of pathology images show that OpenAL can significantly improve the query quality of target class samples and achieve higher performance than current state-of-the-art AL methods. Code is available at https://github.com/miccaiif/OpenAL.

Kexue Fu, Xiaoyuan Luo, Linhao Qu et al.

The expensive fine-grained annotation and data scarcity have become the primary obstacles for the widespread adoption of deep learning-based Whole Slide Images (WSI) classification algorithms in clinical practice. Unlike few-shot learning methods in natural images that can leverage the labels of each image, existing few-shot WSI classification methods only utilize a small number of fine-grained labels or weakly supervised slide labels for training in order to avoid expensive fine-grained annotation. They lack sufficient mining of available WSIs, severely limiting WSI classification performance. To address the above issues, we propose a novel and efficient dual-tier few-shot learning paradigm for WSI classification, named FAST. FAST consists of a dual-level annotation strategy and a dual-branch classification framework. Firstly, to avoid expensive fine-grained annotation, we collect a very small number of WSIs at the slide level, and annotate an extremely small number of patches. Then, to fully mining the available WSIs, we use all the patches and available patch labels to build a cache branch, which utilizes the labeled patches to learn the labels of unlabeled patches and through knowledge retrieval for patch classification. In addition to the cache branch, we also construct a prior branch that includes learnable prompt vectors, using the text encoder of visual-language models for patch classification. Finally, we integrate the results from both branches to achieve WSI classification. Extensive experiments on binary and multi-class datasets demonstrate that our proposed method significantly surpasses existing few-shot classification methods and approaches the accuracy of fully supervised methods with only 0.22$\%$ annotation costs. All codes and models will be publicly available on https://github.com/fukexue/FAST.

Linhao Qu, Xiaoyuan Luo, Shaolei Liu et al.

Multiple Instance Learning (MIL) is widely used in analyzing histopathological Whole Slide Images (WSIs). However, existing MIL methods do not explicitly model the data distribution, and instead they only learn a bag-level or instance-level decision boundary discriminatively by training a classifier. In this paper, we propose DGMIL: a feature distribution guided deep MIL framework for WSI classification and positive patch localization. Instead of designing complex discriminative network architectures, we reveal that the inherent feature distribution of histopathological image data can serve as a very effective guide for instance classification. We propose a cluster-conditioned feature distribution modeling method and a pseudo label-based iterative feature space refinement strategy so that in the final feature space the positive and negative instances can be easily separated. Experiments on the CAMELYON16 dataset and the TCGA Lung Cancer dataset show that our method achieves new SOTA for both global classification and positive patch localization tasks.

Linhao Qu, Siyu Liu, Xiaoyu Liu et al.

Histopathological images contain abundant phenotypic information and pathological patterns, which are the gold standards for disease diagnosis and essential for the prediction of patient prognosis and treatment outcome. In recent years, computer-automated analysis techniques for histopathological images have been urgently required in clinical practice, and deep learning methods represented by convolutional neural networks have gradually become the mainstream in the field of digital pathology. However, obtaining large numbers of fine-grained annotated data in this field is a very expensive and difficult task, which hinders the further development of traditional supervised algorithms based on large numbers of annotated data. More recent studies have started to liberate from the traditional supervised paradigm, and the most representative ones are the studies on weakly supervised learning paradigm based on weak annotation, semi-supervised learning paradigm based on limited annotation, and self-supervised learning paradigm based on pathological image representation learning. These new methods have led a new wave of automatic pathological image diagnosis and analysis targeted at annotation efficiency. With a survey of over 130 papers, we present a comprehensive and systematic review of the latest studies on weakly supervised learning, semi-supervised learning, and self-supervised learning in the field of computational pathology from both technical and methodological perspectives. Finally, we present the key challenges and future trends for these techniques.

Shaolei Liu, Siqi Yin, Linhao Qu et al.

Unsupervised domain adaptation (UDA) aims to learn a model trained on source domain and performs well on unlabeled target domain. In medical image segmentation field, most existing UDA methods depend on adversarial learning to address the domain gap between different image modalities, which is ineffective due to its complicated training process. In this paper, we propose a simple yet effective UDA method based on frequency and spatial domain transfer uner multi-teacher distillation framework. In the frequency domain, we first introduce non-subsampled contourlet transform for identifying domain-invariant and domain-variant frequency components (DIFs and DVFs), and then keep the DIFs unchanged while replacing the DVFs of the source domain images with that of the target domain images to narrow the domain gap. In the spatial domain, we propose a batch momentum update-based histogram matching strategy to reduce the domain-variant image style bias. Experiments on two cross-modality medical image segmentation datasets (cardiac, abdominal) show that our proposed method achieves superior performance compared to state-of-the-art methods.

Linhao Qu, Dingkang Yang, Dan Huang et al.

Current multi-instance learning algorithms for pathology image analysis often require a substantial number of Whole Slide Images for effective training but exhibit suboptimal performance in scenarios with limited learning data. In clinical settings, restricted access to pathology slides is inevitable due to patient privacy concerns and the prevalence of rare or emerging diseases. The emergence of the Few-shot Weakly Supervised WSI Classification accommodates the significant challenge of the limited slide data and sparse slide-level labels for diagnosis. Prompt learning based on the pre-trained models (\eg, CLIP) appears to be a promising scheme for this setting; however, current research in this area is limited, and existing algorithms often focus solely on patch-level prompts or confine themselves to language prompts. This paper proposes a multi-instance prompt learning framework enhanced with pathology knowledge, \ie, integrating visual and textual prior knowledge into prompts at both patch and slide levels. The training process employs a combination of static and learnable prompts, effectively guiding the activation of pre-trained models and further facilitating the diagnosis of key pathology patterns. Lightweight Messenger (self-attention) and Summary (attention-pooling) layers are introduced to model relationships between patches and slides within the same patient data. Additionally, alignment-wise contrastive losses ensure the feature-level alignment between visual and textual learnable prompts for both patches and slides. Our method demonstrates superior performance in three challenging clinical tasks, significantly outperforming comparative few-shot methods.

Dingkang Yang, Mingcheng Li, Linhao Qu et al.

Understanding human intentions (e.g., emotions) from videos has received considerable attention recently. Video streams generally constitute a blend of temporal data stemming from distinct modalities, including natural language, facial expressions, and auditory clues. Despite the impressive advancements of previous works via attention-based paradigms, the inherent temporal asynchrony and modality heterogeneity challenges remain in multimodal sequence fusion, causing adverse performance bottlenecks. To tackle these issues, we propose a Multimodal fusion approach for learning modality-Exclusive and modality-Agnostic representations (MEA) to refine multimodal features and leverage the complementarity across distinct modalities. On the one hand, MEA introduces a predictive self-attention module to capture reliable context dynamics within modalities and reinforce unique features over the modality-exclusive spaces. On the other hand, a hierarchical cross-modal attention module is designed to explore valuable element correlations among modalities over the modality-agnostic space. Meanwhile, a double-discriminator strategy is presented to ensure the production of distinct representations in an adversarial manner. Eventually, we propose a decoupled graph fusion mechanism to enhance knowledge exchange across heterogeneous modalities and learn robust multimodal representations for downstream tasks. Numerous experiments are implemented on three multimodal datasets with asynchronous sequences. Systematic analyses show the necessity of our approach.

Xiaoyu Liu, Linhao Qu, Ziyue Xie et al.

Accurate segmentation of multiple organs of the head, neck, chest, and abdomen from medical images is an essential step in computer-aided diagnosis, surgical navigation, and radiation therapy. In the past few years, with a data-driven feature extraction approach and end-to-end training, automatic deep learning-based multi-organ segmentation method has far outperformed traditional methods and become a new research topic. This review systematically summarizes the latest research in this field. For the first time, from the perspective of full and imperfect annotation, we comprehensively compile 161 studies on deep learning-based multi-organ segmentation in multiple regions such as the head and neck, chest, and abdomen, containing a total of 214 related references. The method based on full annotation summarizes the existing methods from four aspects: network architecture, network dimension, network dedicated modules, and network loss function. The method based on imperfect annotation summarizes the existing methods from two aspects: weak annotation-based methods and semi annotation-based methods. We also summarize frequently used datasets for multi-organ segmentation and discuss new challenges and new research trends in this field.

Xiaoyu Liu, Linhao Qu, Ziyue Xie et al.

The task of labeling multiple organs for segmentation is a complex and time-consuming process, resulting in a scarcity of comprehensively labeled multi-organ datasets while the emergence of numerous partially labeled datasets. Current methods are inadequate in effectively utilizing the supervised information available from these datasets, thereby impeding the progress in improving the segmentation accuracy. This paper proposes a two-stage multi-organ segmentation method based on mutual learning, aiming to improve multi-organ segmentation performance by complementing information among partially labeled datasets. In the first stage, each partial-organ segmentation model utilizes the non-overlapping organ labels from different datasets and the distinct organ features extracted by different models, introducing additional mutual difference learning to generate higher quality pseudo labels for unlabeled organs. In the second stage, each full-organ segmentation model is supervised by fully labeled datasets with pseudo labels and leverages true labels from other datasets, while dynamically sharing accurate features across different models, introducing additional mutual similarity learning to enhance multi-organ segmentation performance. Extensive experiments were conducted on nine datasets that included the head and neck, chest, abdomen, and pelvis. The results indicate that our method has achieved SOTA performance in segmentation tasks that rely on partial labels, and the ablation studies have thoroughly confirmed the efficacy of the mutual learning mechanism.

Linhao Qu, Minghong Duan, Zhiwei Yang et al.

Existing super-resolution models for pathology images can only work in fixed integer magnifications and have limited performance. Though implicit neural network-based methods have shown promising results in arbitrary-scale super-resolution of natural images, it is not effective to directly apply them in pathology images, because pathology images have special fine-grained image textures different from natural images. To address this challenge, we propose a dual-branch framework with an efficient self-texture enhancement mechanism for arbitrary-scale super-resolution of pathology images. Extensive experiments on two public datasets show that our method outperforms both existing fixed-scale and arbitrary-scale algorithms. To the best of our knowledge, this is the first work to achieve arbitrary-scale super-resolution in the field of pathology images. Codes will be available.

Zhiwei Yang, Kexue Fu, Minghong Duan et al.

Weakly supervised semantic segmentation (WSSS) with image-level labels aims to achieve segmentation tasks without dense annotations. However, attributed to the frequent coupling of co-occurring objects and the limited supervision from image-level labels, the challenging co-occurrence problem is widely present and leads to false activation of objects in WSSS. In this work, we devise a 'Separate and Conquer' scheme SeCo to tackle this issue from dimensions of image space and feature space. In the image space, we propose to 'separate' the co-occurring objects with image decomposition by subdividing images into patches. Importantly, we assign each patch a category tag from Class Activation Maps (CAMs), which spatially helps remove the co-context bias and guide the subsequent representation. In the feature space, we propose to 'conquer' the false activation by enhancing semantic representation with multi-granularity knowledge contrast. To this end, a dual-teacher-single-student architecture is designed and tag-guided contrast is conducted, which guarantee the correctness of knowledge and further facilitate the discrepancy among co-contexts. We streamline the multi-staged WSSS pipeline end-to-end and tackle this issue without external supervision. Extensive experiments are conducted, validating the efficiency of our method and the superiority over previous single-staged and even multi-staged competitors on PASCAL VOC and MS COCO. Code is available at https://github.com/zwyang6/SeCo.git.

Linhao Qu, Dan Huang, Shaoting Zhang et al.

Survival analysis stands as a pivotal process in cancer treatment research, crucial for predicting patient survival rates accurately. Recent advancements in data collection techniques have paved the way for enhancing survival predictions by integrating information from multiple modalities. However, real-world scenarios often present challenges with incomplete data, particularly when dealing with censored survival labels. Prior works have addressed missing modalities but have overlooked incomplete labels, which can introduce bias and limit model efficacy. To bridge this gap, we introduce a novel framework that simultaneously handles incomplete data across modalities and censored survival labels. Our approach employs advanced foundation models to encode individual modalities and align them into a universal representation space for seamless fusion. By generating pseudo labels and incorporating uncertainty, we significantly enhance predictive accuracy. The proposed method demonstrates outstanding prediction accuracy in two survival analysis tasks on both employed datasets. This innovative approach overcomes limitations associated with disparate modalities and improves the feasibility of comprehensive survival analysis using multiple large foundation models.

Minghong Duan, Linhao Qu, Shaolei Liu et al.

Implicit neural representations have recently demonstrated promising potential in arbitrary-scale Super-Resolution (SR) of images. Most existing methods predict the pixel in the SR image based on the queried coordinate and ensemble nearby features, overlooking the importance of incorporating high-frequency prior information in images, which results in limited performance in reconstructing high-frequency texture details in images. To address this issue, we propose the Local Implicit Wavelet Transformer (LIWT) to enhance the restoration of high-frequency texture details. Specifically, we decompose the features extracted by an encoder into four sub-bands containing different frequency information using Discrete Wavelet Transform (DWT). We then introduce the Wavelet Enhanced Residual Module (WERM) to transform these four sub-bands into high-frequency priors, followed by utilizing the Wavelet Mutual Projected Fusion (WMPF) and the Wavelet-aware Implicit Attention (WIA) to fully exploit the high-frequency prior information for recovering high-frequency details in images. We conducted extensive experiments on benchmark datasets to validate the effectiveness of LIWT. Both qualitative and quantitative results demonstrate that LIWT achieves promising performance in arbitrary-scale SR tasks, outperforming other state-of-the-art methods. The code is available at https://github.com/dmhdmhdmh/LIWT.

Minghao Han, Dingkang Yang, Jiabei Cheng et al.

Recent advancements in multimodal pre-training models have significantly advanced computational pathology. However, current approaches predominantly rely on visual-language models, which may impose limitations from a molecular perspective and lead to performance bottlenecks. Here, we introduce a Unified Molecule-enhanced Pathology Image REpresentationn Learning framework (UMPIRE). UMPIRE aims to leverage complementary information from gene expression profiles to guide the multimodal pre-training, enhancing the molecular awareness of pathology image representation learning. We demonstrate that this molecular perspective provides a robust, task-agnostic training signal for learning pathology image embeddings. Due to the scarcity of paired data, approximately 4 million entries of spatial transcriptomics gene expression were collected to train the gene encoder. By leveraging powerful pre-trained encoders, UMPIRE aligns the encoders across over 697K pathology image-gene expression pairs. The performance of UMPIRE is demonstrated across various molecular-related downstream tasks, including gene expression prediction, spot classification, and mutation state prediction in whole slide images. Our findings highlight the effectiveness of multimodal data integration and open new avenues for exploring computational pathology enhanced by molecular perspectives. The code and pre-trained weights are available at https://github.com/Hanminghao/UMPIRE.

Minghao Han, Dingkang Yang, Linhao Qu et al.

Recent years have witnessed remarkable progress in multimodal learning within computational pathology. Existing models primarily rely on vision and language modalities; however, language alone lacks molecular specificity and offers limited pathological supervision, leading to representational bottlenecks. In this paper, we propose STAMP, a Spatial Transcriptomics-Augmented Multimodal Pathology representation learning framework that integrates spatially-resolved gene expression profiles to enable molecule-guided joint embedding of pathology images and transcriptomic data. Our study shows that self-supervised, gene-guided training provides a robust and task-agnostic signal for learning pathology image representations. Incorporating spatial context and multi-scale information further enhances model performance and generalizability. To support this, we constructed SpaVis-6M, the largest Visium-based spatial transcriptomics dataset to date, and trained a spatially-aware gene encoder on this resource. Leveraging hierarchical multi-scale contrastive alignment and cross-scale patch localization mechanisms, STAMP effectively aligns spatial transcriptomics with pathology images, capturing spatial structure and molecular variation. We validate STAMP across six datasets and four downstream tasks, where it consistently achieves strong performance. These results highlight the value and necessity of integrating spatially resolved molecular supervision for advancing multimodal learning in computational pathology. The code is included in the supplementary materials. The pretrained weights and SpaVis-6M are available at: https://github.com/Hanminghao/STAMP.

Xiaoyu Liu, Siwen Wei, Linhao Qu et al.

Accurate segmentation of organs at risk in the head and neck is essential for radiation therapy, yet deep learning models often fail on small, complexly shaped organs. While hybrid architectures that combine different models show promise, they typically just concatenate features without exploiting the unique strengths of each component. This results in functional overlap and limited segmentation accuracy. To address these issues, we propose a high uncertainty region-guided multi-architecture collaborative learning (HUR-MACL) model for multi-organ segmentation in the head and neck. This model adaptively identifies high uncertainty regions using a convolutional neural network, and for these regions, Vision Mamba as well as Deformable CNN are utilized to jointly improve their segmentation accuracy. Additionally, a heterogeneous feature distillation loss was proposed to promote collaborative learning between the two architectures in high uncertainty regions to further enhance performance. Our method achieves SOTA results on two public datasets and one private dataset.

Linhao Qu, Chengsheng Zhang, Guihui Li et al.

Breast cancer presents a significant healthcare challenge globally, demanding precise diagnostics and effective treatment strategies, where histopathological examination of Hematoxylin and Eosin (H&E) stained tissue sections plays a central role. Despite its importance, evaluating specific biomarkers like Human Epidermal Growth Factor Receptor 2 (HER2) for personalized treatment remains constrained by the resource-intensive nature of Immunohistochemistry (IHC). Recent strides in deep learning, particularly in image-to-image translation, offer promise in synthesizing IHC-HER2 slides from H\&E stained slides. However, existing methodologies encounter challenges, including managing multiple magnifications in pathology images and insufficient focus on crucial information during translation. To address these issues, we propose a novel model integrating attention mechanisms and multi-magnification information processing. Our model employs a multi-magnification processing strategy to extract and utilize information from various magnifications within pathology images, facilitating robust image translation. Additionally, an attention module within the generative network prioritizes critical information for image distribution translation while minimizing less pertinent details. Rigorous testing on a publicly available breast cancer dataset demonstrates superior performance compared to existing methods, establishing our model as a state-of-the-art solution in advancing pathology image translation from H&E to IHC staining.

Lubin Gan, Jing Zhang, Linhao Qu et al.

The fine-grained classification of brain tumor subtypes from histopathological whole slide images is highly challenging due to subtle morphological variations and the scarcity of annotated data. Although vision-language models have enabled promising zero-shot classification, their ability to capture fine-grained pathological features remains limited, resulting in suboptimal subtype discrimination. To address these challenges, we propose the Fine-Grained Patch Alignment Network (FG-PAN), a novel zero-shot framework tailored for digital pathology. FG-PAN consists of two key modules: (1) a local feature refinement module that enhances patch-level visual features by modeling spatial relationships among representative patches, and (2) a fine-grained text description generation module that leverages large language models to produce pathology-aware, class-specific semantic prototypes. By aligning refined visual features with LLM-generated fine-grained descriptions, FG-PAN effectively increases class separability in both visual and semantic spaces. Extensive experiments on multiple public pathology datasets, including EBRAINS and TCGA, demonstrate that FG-PAN achieves state-of-the-art performance and robust generalization in zero-shot brain tumor subtype classification.

Lubin Gan, Xiaoman Wu, Jing Zhang et al.

Multiple instance learning (MIL) has become the leading approach for extracting discriminative features from whole slide images (WSIs) in computational pathology. Attention-based MIL methods can identify key patches but tend to overlook contextual relationships. Transformer models are able to model interactions but require quadratic computational cost and are prone to overfitting. State space models (SSMs) offer linear complexity, yet shuffling patch order disrupts histological meaning and reduces interpretability. In this work, we introduce SemaMIL, which integrates Semantic Reordering (SR), an adaptive method that clusters and arranges semantically similar patches in sequence through a reversible permutation, with a Semantic-guided Retrieval State Space Module (SRSM) that chooses a representative subset of queries to adjust state space parameters for improved global modeling. Evaluation on four WSI subtype datasets shows that, compared to strong baselines, SemaMIL achieves state-of-the-art accuracy with fewer FLOPs and parameters.

Linhao Qu, Shiman Li, Xiaoyuan Luo et al.

Computer-aided Whole Slide Image (WSI) classification has the potential to enhance the accuracy and efficiency of clinical pathological diagnosis. It is commonly formulated as a Multiple Instance Learning (MIL) problem, where each WSI is treated as a bag and the small patches extracted from the WSI are considered instances within that bag. However, obtaining labels for a large number of bags is a costly and time-consuming process, particularly when utilizing existing WSIs for new classification tasks. This limitation renders most existing WSI classification methods ineffective. To address this issue, we propose a novel WSI classification problem setting, more aligned with clinical practice, termed Weakly Semi-supervised Whole slide image Classification (WSWC). In WSWC, a small number of bags are labeled, while a significant number of bags remain unlabeled. The MIL nature of the WSWC problem, coupled with the absence of patch labels, distinguishes it from typical semi-supervised image classification problems, making existing algorithms for natural images unsuitable for directly solving the WSWC problem. In this paper, we present a concise and efficient framework, named CroCo, to tackle the WSWC problem through two-level Cross Consistency supervision. CroCo comprises two heterogeneous classifier branches capable of performing both instance classification and bag classification. The fundamental idea is to establish cross-consistency supervision at both the bag-level and instance-level between the two branches during training. Extensive experiments conducted on four datasets demonstrate that CroCo achieves superior bag classification and instance classification performance compared to other comparative methods when limited WSIs with bag labels are available. To the best of our knowledge, this paper presents for the first time the WSWC problem and gives a successful resolution.

Chengsheng Zhang, Linhao Qu, Xiaoyu Liu et al.

Survival analysis using whole-slide images (WSIs) is crucial in cancer research. Despite significant successes, pathology images typically only provide slide-level labels, which hinders the learning of discriminative representations from gigapixel WSIs. With the rapid advancement of high-throughput sequencing technologies, multimodal survival analysis integrating pathology images and genomics data has emerged as a promising approach. We propose a Multi-Expert Mamba (ME-Mamba) system that captures discriminative pathological and genomic features while enabling efficient integration of both modalities. This approach achieves complementary information fusion without losing critical information from individual modalities, thereby facilitating accurate cancer survival analysis. Specifically, we first introduce a Pathology Expert and a Genomics Expert to process unimodal data separately. Both experts are designed with Mamba architectures that incorporate conventional scanning and attention-based scanning mechanisms, allowing them to extract discriminative features from long instance sequences containing substantial redundant or irrelevant information. Second, we design a Synergistic Expert responsible for modality fusion. It explicitly learns token-level local correspondences between the two modalities via Optimal Transport, and implicitly enhances distribution consistency through a global cross-modal fusion loss based on Maximum Mean Discrepancy. The fused feature representations are then passed to a mamba backbone for further integration. Through the collaboration of the Pathology Expert, Genomics Expert, and Synergistic Expert, our method achieves stable and accurate survival analysis with relatively low computational complexity. Extensive experimental results on five datasets in The Cancer Genome Atlas (TCGA) demonstrate our state-of-the-art performance.

Zijiang Liu, Xiaoyu Liu, Linhao Qu et al.

Accurate segmentation of brain metastases (BMs) in MR image is crucial for the diagnosis and follow-up of patients. Methods based on deep convolutional neural networks (CNNs) have achieved high segmentation performance. However, due to the loss of critical feature information caused by convolutional and pooling operations, CNNs still face great challenges in small BMs segmentation. Besides, BMs are irregular and easily confused with healthy tissues, which makes it difficult for the model to effectively learn tumor structure during training. To address these issues, this paper proposes a novel model called feature-guided attention network with curriculum learning (FANCL). Based on CNNs, FANCL utilizes the input image and its feature to establish the intrinsic connections between metastases of different sizes, which can effectively compensate for the loss of high-level feature from small tumors with the information of large tumors. Furthermore, FANCL applies the voxel-level curriculum learning strategy to help the model gradually learn the structure and details of BMs. And baseline models of varying depths are employed as curriculum-mining networks for organizing the curriculum progression. The evaluation results on the BraTS-METS 2023 dataset indicate that FANCL significantly improves the segmentation performance, confirming the effectiveness of our method.

Minghong Duan, Linhao Qu, Zhiwei Yang et al.

High-quality whole-slide scanning is expensive, complex, and time-consuming, thus limiting the acquisition and utilization of high-resolution histopathology images in daily clinical work. Deep learning-based single-image super-resolution (SISR) techniques provide an effective way to solve this problem. However, the existing SISR models applied in histopathology images can only work in fixed integer scaling factors, decreasing their applicability. Though methods based on implicit neural representation (INR) have shown promising results in arbitrary-scale super-resolution (SR) of natural images, applying them directly to histopathology images is inadequate because they have unique fine-grained image textures different from natural images. Thus, we propose an Implicit Self-Texture Enhancement-based dual-branch framework (ISTE) for arbitrary-scale SR of histopathology images to address this challenge. The proposed ISTE contains a feature aggregation branch and a texture learning branch. We employ the feature aggregation branch to enhance the learning of the local details for SR images while utilizing the texture learning branch to enhance the learning of high-frequency texture details. Then, we design a two-stage texture enhancement strategy to fuse the features from the two branches to obtain the SR images. Experiments on publicly available datasets, including TMA, HistoSR, and the TCGA lung cancer datasets, demonstrate that ISTE outperforms existing fixed-scale and arbitrary-scale SR algorithms across various scaling factors. Additionally, extensive experiments have shown that the histopathology images reconstructed by the proposed ISTE are applicable to downstream pathology image analysis tasks.

Linhao Qu, Xiaoyuan Luo, Kexue Fu et al.

This paper introduces the novel concept of few-shot weakly supervised learning for pathology Whole Slide Image (WSI) classification, denoted as FSWC. A solution is proposed based on prompt learning and the utilization of a large language model, GPT-4. Since a WSI is too large and needs to be divided into patches for processing, WSI classification is commonly approached as a Multiple Instance Learning (MIL) problem. In this context, each WSI is considered a bag, and the obtained patches are treated as instances. The objective of FSWC is to classify both bags and instances with only a limited number of labeled bags. Unlike conventional few-shot learning problems, FSWC poses additional challenges due to its weak bag labels within the MIL framework. Drawing inspiration from the recent achievements of vision-language models (V-L models) in downstream few-shot classification tasks, we propose a two-level prompt learning MIL framework tailored for pathology, incorporating language prior knowledge. Specifically, we leverage CLIP to extract instance features for each patch, and introduce a prompt-guided pooling strategy to aggregate these instance features into a bag feature. Subsequently, we employ a small number of labeled bags to facilitate few-shot prompt learning based on the bag features. Our approach incorporates the utilization of GPT-4 in a question-and-answer mode to obtain language prior knowledge at both the instance and bag levels, which are then integrated into the instance and bag level language prompts. Additionally, a learnable component of the language prompts is trained using the available few-shot labeled data. We conduct extensive experiments on three real WSI datasets encompassing breast cancer, lung cancer, and cervical cancer, demonstrating the notable performance of the proposed method in bag and instance classification. All codes will be available.

Linhao Qu, Shaolei Liu, Manning Wang et al.

Image fusion is a technique to integrate information from multiple source images with complementary information to improve the richness of a single image. Due to insufficient task-specific training data and corresponding ground truth, most existing end-to-end image fusion methods easily fall into overfitting or tedious parameter optimization processes. Two-stage methods avoid the need of large amount of task-specific training data by training encoder-decoder network on large natural image datasets and utilizing the extracted features for fusion, but the domain gap between natural images and different fusion tasks results in limited performance. In this study, we design a novel encoder-decoder based image fusion framework and propose a destruction-reconstruction based self-supervised training scheme to encourage the network to learn task-specific features. Specifically, we propose three destruction-reconstruction self-supervised auxiliary tasks for multi-modal image fusion, multi-exposure image fusion and multi-focus image fusion based on pixel intensity non-linear transformation, brightness transformation and noise transformation, respectively. In order to encourage different fusion tasks to promote each other and increase the generalizability of the trained network, we integrate the three self-supervised auxiliary tasks by randomly choosing one of them to destroy a natural image in model training. In addition, we design a new encoder that combines CNN and Transformer for feature extraction, so that the trained model can exploit both local and global information. Extensive experiments on multi-modal image fusion, multi-exposure image fusion and multi-focus image fusion tasks demonstrate that our proposed method achieves the state-of-the-art performance in both subjective and objective evaluations. The code will be publicly available soon.

Linhao Qu, Shaolei Liu, Manning Wang et al.

In this paper, we propose TransMEF, a transformer-based multi-exposure image fusion framework that uses self-supervised multi-task learning. The framework is based on an encoder-decoder network, which can be trained on large natural image datasets and does not require ground truth fusion images. We design three self-supervised reconstruction tasks according to the characteristics of multi-exposure images and conduct these tasks simultaneously using multi-task learning; through this process, the network can learn the characteristics of multi-exposure images and extract more generalized features. In addition, to compensate for the defect in establishing long-range dependencies in CNN-based architectures, we design an encoder that combines a CNN module with a transformer module. This combination enables the network to focus on both local and global information. We evaluated our method and compared it to 11 competitive traditional and deep learning-based methods on the latest released multi-exposure image fusion benchmark dataset, and our method achieved the best performance in both subjective and objective evaluations.