In histopathology, intelligent diagnosis of Whole Slide Images (WSIs) is essential for automating and objectifying diagnoses, reducing the workload of pathologists. However, diagnostic models often face the challenge of forgetting previously learned data during incremental training on datasets from different sources. To address this issue, we propose a new framework PaGMIL to mitigate catastrophic forgetting in breast cancer WSI classification. Our framework introduces two key components into the common MIL model architecture. First, it leverages microscopic pathological prior to select more accurate and diverse representative patches for MIL. Secondly, it trains separate classification heads for each task and uses macroscopic pathological prior knowledge, treating the thumbnail as a prompt guide (PG) to select the appropriate classification head. We evaluate the continual learning performance of PaGMIL across several public breast cancer datasets. PaGMIL achieves a better balance between the performance of the current task and the retention of previous tasks, outperforming other continual learning methods. Our code will be open-sourced upon acceptance.
Pathological diagnosis plays a critical role in clinical practice, where the whole slide images (WSIs) are widely applied. Through a two-stage paradigm, recent deep learning approaches enhance the WSI analysis with tile-level feature extracting and slide-level feature modeling. Current Transformer models achieved improvement in the efficiency and accuracy to previous multiple instance learning based approaches. However, three core limitations persist, as they do not: (1) robustly address the modeling on variable scales for different slides, (2) effectively balance model complexity and data availability, and (3) balance training efficiency and inference performance. To explicitly address them, we propose a novel model for slide modeling, PathRWKV. Via a recurrent structure, we enable the model for dynamic perceptible tiles in slide-level modeling, which novelly enables the prediction on all tiles in the inference stage. Moreover, we employ linear attention instead of conventional matrix multiplication attention to reduce model complexity and overfitting problem. Lastly, we hinge multi-task learning to enable modeling on versatile tasks simultaneously, improving training efficiency, and asynchronous structure design to draw an effective conclusion on all tiles during inference, enhancing inference performance. Experimental results suggest that PathRWKV outperforms the current state-of-the-art methods in various downstream tasks on multiple datasets. The code and datasets are publicly available.
The role of artificial intelligence (AI) in pathology has evolved from aiding diagnostics to uncovering predictive morphological patterns in whole slide images (WSIs). Recently, foundation models (FMs) leveraging self-supervised pre-training have been widely advocated as a universal solution for diverse downstream tasks. However, open questions remain about their clinical applicability and generalization advantages over end-to-end learning using task-specific (TS) models. Here, we focused on AI with clinical-grade performance for prostate cancer diagnosis and Gleason grading. We present the largest validation of AI for this task, using over 100,000 core needle biopsies from 7,342 patients across 15 sites in 11 countries. We compared two FMs with a fully end-to-end TS model in a multiple instance learning framework. Our findings challenge assumptions that FMs universally outperform TS models. While FMs demonstrated utility in data-scarce scenarios, their performance converged with - and was in some cases surpassed by - TS models when sufficient labeled training data were available. Notably, extensive task-specific training markedly reduced clinically significant misgrading, misdiagnosis of challenging morphologies, and variability across different WSI scanners. Additionally, FMs used up to 35 times more energy than the TS model, raising concerns about their sustainability. Our results underscore that while FMs offer clear advantages for rapid prototyping and research, their role as a universal solution for clinically applicable medical AI remains uncertain. For high-stakes clinical applications, rigorous validation and consideration of task-specific training remain critically important. We advocate for integrating the strengths of FMs and end-to-end learning to achieve robust and resource-efficient AI pathology solutions fit for clinical use.
Accurate tumor detection in digital pathology whole-slide images (WSIs) is crucial for cancer diagnosis and treatment planning. Multiple Instance Learning (MIL) has emerged as a widely used approach for weakly-supervised tumor detection with large-scale data without the need for manual annotations. However, traditional MIL methods often depend on classification tasks that require tumor-free cases as negative examples, which are challenging to obtain in real-world clinical workflows, especially for surgical resection specimens. We address this limitation by reformulating tumor detection as a regression task, estimating tumor percentages from WSIs, a clinically available target across multiple cancer types. In this paper, we provide an analysis of the proposed weakly-supervised regression framework by applying it to multiple organs, specimen types and clinical scenarios. We characterize the robustness of our framework to tumor percentage as a noisy regression target, and introduce a novel concept of amplification technique to improve tumor detection sensitivity when learning from small tumor regions. Finally, we provide interpretable insights into the model's predictions by analyzing visual attention and logit maps. Our code is available at https://github.com/DIAGNijmegen/tumor-percentage-mil-regression.
Marine ecosystem monitoring via Passive Acoustic Monitoring (PAM) generates vast data, but deep learning often requires precise annotations and short segments. We introduce DSMIL-LocNet, a Multiple Instance Learning framework for whale call detection and localization using only bag-level labels. Our dual-stream model processes 2-30 minute audio segments, leveraging spectral and temporal features with attention-based instance selection. Tests on Antarctic whale data show longer contexts improve classification (F1: 0.8-0.9) while medium instances ensure localization precision (0.65-0.70). This suggests MIL can enhance scalable marine monitoring. Code: https://github.com/Ragib-Amin-Nihal/DSMIL-Loc
Deploying digital pathology models across medical centers is challenging due to distribution shifts. Recent advances in domain generalization improve model transferability in terms of aggregated performance measured by the Area Under Curve (AUC). However, clinical regulations often require to control the transferability of other metrics, such as prescribed sensitivity levels. We introduce a novel approach to control the sensitivity of whole slide image (WSI) classification models, based on optimal transport and Multiple Instance Learning (MIL). Validated across multiple cohorts and tasks, our method enables robust sensitivity control with only a handful of calibration samples, providing a practical solution for reliable deployment of computational pathology systems.
While deep learning methods have shown great promise in improving the effectiveness of prostate cancer (PCa) diagnosis by detecting suspicious lesions from trans-rectal ultrasound (TRUS), they must overcome multiple simultaneous challenges. There is high heterogeneity in tissue appearance, significant class imbalance in favor of benign examples, and scarcity in the number and quality of ground truth annotations available to train models. Failure to address even a single one of these problems can result in unacceptable clinical outcomes.We propose TRUSWorthy, a carefully designed, tuned, and integrated system for reliable PCa detection. Our pipeline integrates self-supervised learning, multiple-instance learning aggregation using transformers, random-undersampled boosting and ensembling: these address label scarcity, weak labels, class imbalance, and overconfidence, respectively. We train and rigorously evaluate our method using a large, multi-center dataset of micro-ultrasound data. Our method outperforms previous state-of-the-art deep learning methods in terms of accuracy and uncertainty calibration, with AUROC and balanced accuracy scores of 79.9% and 71.5%, respectively. On the top 20% of predictions with the highest confidence, we can achieve a balanced accuracy of up to 91%. The success of TRUSWorthy demonstrates the potential of integrated deep learning solutions to meet clinical needs in a highly challenging deployment setting, and is a significant step towards creating a trustworthy system for computer-assisted PCa diagnosis.
The proliferation of misinformation, such as rumors on social media, has drawn significant attention, prompting various expressions of stance among users. Although rumor detection and stance detection are distinct tasks, they can complement each other. Rumors can be identified by cross-referencing stances in related posts, and stances are influenced by the nature of the rumor. However, existing stance detection methods often require post-level stance annotations, which are costly to obtain. We propose a novel LLM-enhanced MIL approach to jointly predict post stance and claim class labels, supervised solely by claim labels, using an undirected microblog propagation model. Our weakly supervised approach relies only on bag-level labels of claim veracity, aligning with multi-instance learning (MIL) principles. To achieve this, we transform the multi-class problem into multiple MIL-based binary classification problems. We then employ a discriminative attention layer to aggregate the outputs from these classifiers into finer-grained classes. Experiments conducted on three rumor datasets and two stance datasets demonstrate the effectiveness of our approach, highlighting strong connections between rumor veracity and expressed stances in responding posts. Our method shows promising performance in joint rumor and stance detection compared to the state-of-the-art methods.
Multiple instance learning (MIL)-based framework has become the mainstream for processing the whole slide image (WSI) with giga-pixel size and hierarchical image context in digital pathology. However, these methods heavily depend on a substantial number of bag-level labels and solely learn from the original slides, which are easily affected by variations in data distribution. Recently, vision language model (VLM)-based methods introduced the language prior by pre-training on large-scale pathological image-text pairs. However, the previous text prompt lacks the consideration of pathological prior knowledge, therefore does not substantially boost the model's performance. Moreover, the collection of such pairs and the pre-training process are very time-consuming and source-intensive.To solve the above problems, we propose a dual-scale vision-language multiple instance learning (ViLa-MIL) framework for whole slide image classification. Specifically, we propose a dual-scale visual descriptive text prompt based on the frozen large language model (LLM) to boost the performance of VLM effectively. To transfer the VLM to process WSI efficiently, for the image branch, we propose a prototype-guided patch decoder to aggregate the patch features progressively by grouping similar patches into the same prototype; for the text branch, we introduce a context-guided text decoder to enhance the text features by incorporating the multi-granular image contexts. Extensive studies on three multi-cancer and multi-center subtyping datasets demonstrate the superiority of ViLa-MIL.
Diagnosing diseases through histopathology whole slide images (WSIs) is fundamental in modern pathology but is challenged by the gigapixel scale and complexity of WSIs. Trained histopathologists overcome this challenge by navigating the WSI, looking for relevant patches, taking notes, and compiling them to produce a final holistic diagnostic. Traditional AI approaches, such as multiple instance learning and transformer-based models, fail short of such a holistic, iterative, multi-scale diagnostic procedure, limiting their adoption in the real-world. We introduce PathFinder, a multi-modal, multi-agent framework that emulates the decision-making process of expert pathologists. PathFinder integrates four AI agents, the Triage Agent, Navigation Agent, Description Agent, and Diagnosis Agent, that collaboratively navigate WSIs, gather evidence, and provide comprehensive diagnoses with natural language explanations. The Triage Agent classifies the WSI as benign or risky; if risky, the Navigation and Description Agents iteratively focus on significant regions, generating importance maps and descriptive insights of sampled patches. Finally, the Diagnosis Agent synthesizes the findings to determine the patient's diagnostic classification. Our Experiments show that PathFinder outperforms state-of-the-art methods in skin melanoma diagnosis by 8% while offering inherent explainability through natural language descriptions of diagnostically relevant patches. Qualitative analysis by pathologists shows that the Description Agent's outputs are of high quality and comparable to GPT-4o. PathFinder is also the first AI-based system to surpass the average performance of pathologists in this challenging melanoma classification task by 9%, setting a new record for efficient, accurate, and interpretable AI-assisted diagnostics in pathology. Data, code and models available at https://pathfinder-dx.github.io/
Multiple Instance Learning (MIL) for whole slide image (WSI) analysis in computational pathology often neglects instance-level learning as supervision is typically provided only at the bag level. In this work, we present LadderMIL, a framework designed to improve MIL through two perspectives: (1) employing instance-level supervision and (2) learning inter-instance contextual information at bag level. Firstly, we propose a novel Coarse-to-Fine Self-Distillation (CFSD) paradigm that probes and distils a network trained with bag-level information to adaptively obtain instance-level labels which could effectively provide the instance-level supervision for the same network in a self-improving way. Secondly, to capture inter-instance contextual information in WSI, we propose a Contextual Ecoding Generator (CEG), which encodes the contextual appearance of instances within a bag. We also theoretically and empirically prove the instance-level learnability of CFSD. Our LadderMIL is evaluated on multiple clinically relevant benchmarking tasks including breast cancer receptor status classification, multi-class subtype classification, tumour classification, and prognosis prediction. Average improvements of 8.1%, 11% and 2.4% in AUC, F1-score, and C-index, respectively, are demonstrated across the five benchmarks, compared to the best baseline.
Emotions play a crucial role in human behavior and decision-making, making emotion recognition a key area of interest in human-computer interaction (HCI). This study addresses the challenges of emotion recognition by integrating facial expression analysis with electroencephalogram (EEG) signals, introducing a novel multimodal framework-Milmer. The proposed framework employs a transformer-based fusion approach to effectively integrate visual and physiological modalities. It consists of an EEG preprocessing module, a facial feature extraction and balancing module, and a cross-modal fusion module. To enhance visual feature extraction, we fine-tune a pre-trained Swin Transformer on emotion-related datasets. Additionally, a cross-attention mechanism is introduced to balance token representation across modalities, ensuring effective feature integration. A key innovation of this work is the adoption of a multiple instance learning (MIL) approach, which extracts meaningful information from multiple facial expression images over time, capturing critical temporal dynamics often overlooked in previous studies. Extensive experiments conducted on the DEAP dataset demonstrate the superiority of the proposed framework, achieving a classification accuracy of 96.72% in the four-class emotion recognition task. Ablation studies further validate the contributions of each module, highlighting the significance of advanced feature extraction and fusion strategies in enhancing emotion recognition performance. Our code are available at https://github.com/liangyubuaa/Milmer.
Whole Slide Imaging (WSI), which involves high-resolution digital scans of pathology slides, has become the gold standard for cancer diagnosis, but its gigapixel resolution and the scarcity of annotated datasets present challenges for deep learning models. Multiple Instance Learning (MIL), a widely-used weakly supervised approach, bypasses the need for patch-level annotations. However, conventional MIL methods overlook the spatial relationships between patches, which are crucial for tasks such as cancer grading and diagnosis. To address this, graph-based approaches have gained prominence by incorporating spatial information through node connections. Despite their potential, both MIL and graph-based models are vulnerable to learning spurious associations, like color variations in WSIs, affecting their robustness. In this dissertation, we conduct an extensive comparison of multiple graph construction techniques, MIL models, graph-MIL approaches, and interventional training, introducing a new framework, Graph-based Multiple Instance Learning with Interventional Training (GMIL-IT), for WSI classification. We evaluate their impact on model generalization through domain shift analysis and demonstrate that graph-based models alone achieve the generalization initially anticipated from interventional training. Our code is available here: github.com/ritamartinspereira/GMIL-IT
Bone metastasis analysis is a significant challenge in pathology and plays a critical role in determining patient quality of life and treatment strategies. The microenvironment and specific tissue structures are essential for pathologists to predict the primary bone cancer origins and primary bone cancer subtyping. By digitizing bone tissue sections into whole slide images (WSIs) and leveraging deep learning to model slide embeddings, this analysis can be enhanced. However, tumor metastasis involves complex multivariate interactions with diverse bone tissue structures, which traditional WSI analysis methods such as multiple instance learning (MIL) fail to capture. Moreover, graph neural networks (GNNs), limited to modeling pairwise relationships, are hard to represent high-order biological associations. To address these challenges, we propose a dynamic hypergraph neural network (DyHG) that overcomes the edge construction limitations of traditional graph representations by connecting multiple nodes via hyperedges. A low-rank strategy is used to reduce the complexity of parameters in learning hypergraph structures, while a Gumbel-Softmax-based sampling strategy optimizes the patch distribution across hyperedges. An MIL aggregator is then used to derive a graph-level embedding for comprehensive WSI analysis. To evaluate the effectiveness of DyHG, we construct two large-scale datasets for primary bone cancer origins and subtyping classification based on real-world bone metastasis scenarios. Extensive experiments demonstrate that DyHG significantly outperforms state-of-the-art (SOTA) baselines, showcasing its ability to model complex biological interactions and improve the accuracy of bone metastasis analysis.
Large language models (LLMs) exhibit remarkable capabilities in visual inspection of medical time-series data, achieving proficiency comparable to human clinicians. However, their broad scope limits domain-specific precision, and proprietary weights hinder fine-tuning for specialized datasets. In contrast, small specialized models (SSMs) excel in targeted tasks but lack the contextual reasoning required for complex clinical decision-making. To address these challenges, we propose ConMIL (Conformalized Multiple Instance Learning), a decision-support SSM that integrates seamlessly with LLMs. By using Multiple Instance Learning (MIL) to identify clinically significant signal segments and conformal prediction for calibrated set-valued outputs, ConMIL enhances LLMs' interpretative capabilities for medical time-series analysis. Experimental results demonstrate that ConMIL significantly improves the performance of state-of-the-art LLMs, such as ChatGPT4.0 and Qwen2-VL-7B. Specifically, \ConMIL{}-supported Qwen2-VL-7B achieves 94.92% and 96.82% precision for confident samples in arrhythmia detection and sleep staging, compared to standalone LLM accuracy of 46.13% and 13.16%. These findings highlight the potential of ConMIL to bridge task-specific precision and broader contextual reasoning, enabling more reliable and interpretable AI-driven clinical decision support.
Computed tomography (CT) and clinical numeric data are essential modalities for cancer evaluation, but building large-scale multimodal training datasets for developing medical foundation models remains challenging due to the structural complexity of multi-slice CT data and high cost of expert annotation. In this study, we propose MEDFORM, a multimodal pre-training strategy that guides CT image representation learning using complementary information from clinical data for medical foundation model development. MEDFORM efficiently processes CT slice through multiple instance learning (MIL) and adopts a dual pre-training strategy: first pretraining the CT slice feature extractor using SimCLR-based self-supervised learning, then aligning CT and clinical modalities through cross-modal contrastive learning. Our model was pre-trained on three different cancer types: lung cancer (141,171 slices), breast cancer (8,100 slices), colorectal cancer (10,393 slices). The experimental results demonstrated that this dual pre-training strategy improves cancer classification performance and maintains robust performance in few-shot learning scenarios. Code available at https://github.com/DigitalHealthcareLab/25MultiModalFoundationModel.git
Weakly supervised object localization (WSOL) using classification models trained with only image-class labels remains an important challenge in computer vision. Given their reliance on classification objectives, traditional WSOL methods like class activation mapping focus on the most discriminative object parts, often missing the full spatial extent. In contrast, recent WSOL methods based on vision-language models like CLIP require ground truth classes or external classifiers to produce a localization map, limiting their deployment in downstream tasks. Moreover, methods like GenPromp attempt to address these issues but introduce considerable complexity due to their reliance on conditional denoising processes and intricate prompt learning. This paper introduces Text Distillation for Localization (TeD-Loc), an approach that directly distills knowledge from CLIP text embeddings into the model backbone and produces patch-level localization. Multiple instance learning of these image patches allows for accurate localization and classification using one model without requiring external classifiers. Such integration of textual and visual modalities addresses the longstanding challenge of achieving accurate localization and classification concurrently, as WSOL methods in the literature typically converge at different epochs. Extensive experiments show that leveraging text embeddings and localization cues provides a cost-effective WSOL model. TeD-Loc improves Top-1 LOC accuracy over state-of-the-art models by about 5% on both CUB and ILSVRC datasets, while significantly reducing computational complexity compared to GenPromp.
Ewing's sarcoma (ES), characterized by a high density of small round blue cells without structural organization, presents a significant health concern, particularly among adolescents aged 10 to 19. Artificial intelligence-based systems for automated analysis of histopathological images are promising to contribute to an accurate diagnosis of ES. In this context, this study explores the feature extraction ability of different pre-training strategies for distinguishing ES from other soft tissue or bone sarcomas with similar morphology in digitized tissue microarrays for the first time, as far as we know. Vision-language supervision (VLS) is compared to fully-supervised ImageNet pre-training within a multiple instance learning paradigm. Our findings indicate a substantial improvement in diagnostic accuracy with the adaption of VLS using an in-domain dataset. Notably, these models not only enhance the accuracy of predicted classes but also drastically reduce the number of trainable parameters and computational costs.
Weakly supervised violence detection refers to the technique of training models to identify violent segments in videos using only video-level labels. Among these approaches, multimodal violence detection, which integrates modalities such as audio and optical flow, holds great potential. Existing methods in this domain primarily focus on designing multimodal fusion models to address modality discrepancies. In contrast, we take a different approach; leveraging the inherent discrepancies across modalities in violence event representation to propose a novel multimodal semantic feature alignment method. This method sparsely maps the semantic features of local, transient, and less informative modalities ( such as audio and optical flow ) into the more informative RGB semantic feature space. Through an iterative process, the method identifies the suitable no-zero feature matching subspace and aligns the modality-specific event representations based on this subspace, enabling the full exploitation of information from all modalities during the subsequent modality fusion stage. Building on this, we design a new weakly supervised violence detection framework that consists of unimodal multiple-instance learning for extracting unimodal semantic features, multimodal alignment, multimodal fusion, and final detection. Experimental results on benchmark datasets demonstrate the effectiveness of our method, achieving an average precision (AP) of 86.07% on the XD-Violence dataset. Our code is available at https://github.com/xjpp2016/MAVD.
Weakly supervised segmentation has the potential to greatly reduce the annotation effort for training segmentation models for small structures such as hyper-reflective foci (HRF) in optical coherence tomography (OCT). However, most weakly supervised methods either involve a strong downsampling of input images, or only achieve localization at a coarse resolution, both of which are unsatisfactory for small structures. We propose a novel framework that increases the spatial resolution of a traditional attention-based Multiple Instance Learning (MIL) approach by using Layer-wise Relevance Propagation (LRP) to prompt the Segment Anything Model (SAM~2), and increases recall with iterative inference. Moreover, we demonstrate that replacing MIL with a Compact Convolutional Transformer (CCT), which adds a positional encoding, and permits an exchange of information between different regions of the OCT image, leads to a further and substantial increase in segmentation accuracy.