Uncertainty estimation (UE), as an effective means of quantifying predictive uncertainty, is crucial for safe and reliable decision-making, especially in high-risk scenarios. Existing UE schemes usually assume that there are completely-labeled samples to support fully-supervised learning. In practice, however, many UE tasks often have no sufficiently-labeled data to use, such as the Multiple Instance Learning (MIL) with only weak instance annotations. To bridge this gap, this paper, for the first time, addresses the weakly-supervised issue of Multi-Instance UE (MIUE) and proposes a new baseline scheme, Multi-Instance Residual Evidential Learning (MIREL). Particularly, at the fine-grained instance UE with only weak supervision, we derive a multi-instance residual operator through the Fundamental Theorem of Symmetric Functions. On this operator derivation, we further propose MIREL to jointly model the high-order predictive distribution at bag and instance levels for MIUE. Extensive experiments empirically demonstrate that our MIREL not only could often make existing MIL networks perform better in MIUE, but also could surpass representative UE methods by large margins, especially in instance-level UE tasks. Our source code is available at https://github.com/liupei101/MIREL.
Deep neural networks, including transformers and convolutional neural networks, have significantly improved multivariate time series classification (MTSC). However, these methods often rely on supervised learning, which does not fully account for the sparsity and locality of patterns in time series data (e.g., diseases-related anomalous points in ECG). To address this challenge, we formally reformulate MTSC as a weakly supervised problem, introducing a novel multiple-instance learning (MIL) framework for better localization of patterns of interest and modeling time dependencies within time series. Our novel approach, TimeMIL, formulates the temporal correlation and ordering within a time-aware MIL pooling, leveraging a tokenized transformer with a specialized learnable wavelet positional token. The proposed method surpassed 26 recent state-of-the-art methods, underscoring the effectiveness of the weakly supervised TimeMIL in MTSC. The code will be available at https://github.com/xiwenc1/TimeMIL.
Early detection of cancer can help improve patient prognosis by early intervention. Head and neck cancer is diagnosed in specialist centres after a surgical biopsy, however, there is a potential for these to be missed leading to delayed diagnosis. To overcome these challenges, we present an attention based pipeline that identifies suspected lesions, segments, and classifies them as non-dysplastic, dysplastic and cancerous lesions. We propose (a) a vision transformer based Mask R-CNN network for lesion detection and segmentation of clinical images, and (b) Multiple Instance Learning (MIL) based scheme for classification. Current results show that the segmentation model produces segmentation masks and bounding boxes with up to 82% overlap accuracy score on unseen external test data and surpassing reviewed segmentation benchmarks. Next, a classification F1-score of 85% on the internal cohort test set. An app has been developed to perform lesion segmentation taken via a smart device. Future work involves employing endoscopic video data for precise early detection and prognosis.
Deep learning models have revolutionized the field of medical image analysis, due to their outstanding performances. However, they are sensitive to spurious correlations, often taking advantage of dataset bias to improve results for in-domain data, but jeopardizing their generalization capabilities. In this paper, we propose to limit the amount of information these models use to reach the final classification, by using a multiple instance learning (MIL) framework. MIL forces the model to use only a (small) subset of patches in the image, identifying discriminative regions. This mimics the clinical procedures, where medical decisions are based on localized findings. We evaluate our framework on two medical applications: skin cancer diagnosis using dermoscopy and breast cancer diagnosis using mammography. Our results show that using only a subset of the patches does not compromise diagnostic performance for in-domain data, compared to the baseline approaches. However, our approach is more robust to shifts in patient demographics, while also providing more detailed explanations about which regions contributed to the decision. Code is available at: https://github.com/diogojpa99/MedicalMultiple-Instance-Learning.
Survival prediction is a complex ordinal regression task that aims to predict the survival coefficient ranking among a cohort of patients, typically achieved by analyzing patients' whole slide images. Existing deep learning approaches mainly adopt multiple instance learning or graph neural networks under weak supervision. Most of them are unable to uncover the diverse interactions between different types of biological entities(\textit{e.g.}, cell cluster and tissue block) across multiple scales, while such interactions are crucial for patient survival prediction. In light of this, we propose a novel multi-scale heterogeneity-aware hypergraph representation framework. Specifically, our framework first constructs a multi-scale heterogeneity-aware hypergraph and assigns each node with its biological entity type. It then mines diverse interactions between nodes on the graph structure to obtain a global representation. Experimental results demonstrate that our method outperforms state-of-the-art approaches on three benchmark datasets. Code is publicly available at \href{https://github.com/Hanminghao/H2GT}{https://github.com/Hanminghao/H2GT}.
Transportation mode recognition (TMR) is a critical component of human activity recognition (HAR) that focuses on understanding and identifying how people move within transportation systems. It is commonly based on leveraging inertial, location, or both types of signals, captured by modern smartphone devices. Each type has benefits (such as increased effectiveness) and drawbacks (such as increased battery consumption) depending on the transportation mode (TM). Combining the two types is challenging as they exhibit significant differences such as very different sampling rates. This paper focuses on the TMR task and proposes an approach for combining the two types of signals in an effective and robust classifier. Our network includes two sub-networks for processing acceleration and location signals separately, using different window sizes for each signal. The two sub-networks are designed to also embed the two types of signals into the same space so that we can then apply an attention-based multiple-instance learning classifier to recognize TM. We use very low sampling rates for both signal types to reduce battery consumption. We evaluate the proposed methodology on a publicly available dataset and compare against other well known algorithms.
The interactions between tumor cells and the tumor microenvironment (TME) dictate therapeutic efficacy of radiation and many systemic therapies in breast cancer. However, to date, there is not a widely available method to reproducibly measure tumor and immune phenotypes for each patient's tumor. Given this unmet clinical need, we applied multiple instance learning (MIL) algorithms to assess activity of ten biologically relevant pathways from the hematoxylin and eosin (H&E) slide of primary breast tumors. We employed different feature extraction approaches and state-of-the-art model architectures. Using binary classification, our models attained area under the receiver operating characteristic (AUROC) scores above 0.70 for nearly all gene expression pathways and on some cases, exceeded 0.80. Attention maps suggest that our trained models recognize biologically relevant spatial patterns of cell sub-populations from H&E. These efforts represent a first step towards developing computational H&E biomarkers that reflect facets of the TME and hold promise for augmenting precision oncology.
This study introduces RT-HMD, a Hardware-based Malware Detector (HMD) for mobile devices, that refines malware representation in segmented time-series through a Multiple Instance Learning (MIL) approach. We address the mislabeling issue in real-time HMDs, where benign segments in malware time-series incorrectly inherit malware labels, leading to increased false positives. Utilizing the proposed Malicious Discriminative Score within the MIL framework, RT-HMD effectively identifies localized malware behaviors, thereby improving the predictive accuracy. Empirical analysis, using a hardware telemetry dataset collected from a mobile platform across 723 benign and 1033 malware samples, shows a 5% precision boost while maintaining recall, outperforming baselines affected by mislabeled benign segments.
Crack detection has become an indispensable, interesting yet challenging task in the computer vision community. Specially, pavement cracks have a highly complex spatial structure, a low contrasting background and a weak spatial continuity, posing a significant challenge to an effective crack detection method. In this paper, we address these problems from a view that utilizes contexts of the cracks and propose an end-to-end deep learning method to model the context information flow. To precisely localize crack from an image, it is critical to effectively extract and aggregate multi-granularity context, including the fine-grained local context around the cracks (in spatial-level) and the coarse-grained semantics (in segment-level). Concretely, in Convolutional Neural Network (CNN), low-level features extracted by the shallow layers represent the local information, while the deep layers extract the semantic features. Additionally, a second main insight in this work is that the semantic context should be an guidance to local context feature. By the above insights, the proposed method we first apply the dilated convolution as the backbone feature extractor to model local context, then we build a context guidance module to leverage semantic context to guide local feature extraction at multiple stages. To handle label alignment between stages, we apply the Multiple Instance Learning (MIL) strategy to align the high-level feature to the low-level ones in the stage-wise context flow. In addition, compared with these public crack datasets, to our best knowledge, we release the largest, most complex and most challenging Bitumen Pavement Crack (BPC) dataset. The experimental results on the three crack datasets demonstrate that the proposed method performs well and outperforms the current state-of-the-art methods.
Accurate cancer diagnosis remains a critical challenge in digital pathology, largely due to the gigapixel size and complex spatial relationships present in whole slide images. Traditional multiple instance learning (MIL) methods often struggle with these intricacies, especially in preserving the necessary context for accurate diagnosis. In response, we introduce a novel framework named Semantics-Aware Attention Guidance (SAG), which includes 1) a technique for converting diagnostically relevant entities into attention signals, and 2) a flexible attention loss that efficiently integrates various semantically significant information, such as tissue anatomy and cancerous regions. Our experiments on two distinct cancer datasets demonstrate consistent improvements in accuracy, precision, and recall with two state-of-the-art baseline models. Qualitative analysis further reveals that the incorporation of heuristic guidance enables the model to focus on regions critical for diagnosis. SAG is not only effective for the models discussed here, but its adaptability extends to any attention-based diagnostic model. This opens up exciting possibilities for further improving the accuracy and efficiency of cancer diagnostics.
Large language models (LLMs) are being increasingly tuned to power complex generation tasks such as writing, fact-seeking, querying and reasoning. Traditionally, human or model feedback for evaluating and further tuning LLM performance has been provided at the response level, enabling faster and more cost-effective assessments. However, recent works (Amplayo et al. [2022], Wu et al. [2023]) indicate that sentence-level labels may provide more accurate and interpretable feedback for LLM optimization. In this work, we introduce methods to disaggregate response-level labels into sentence-level (pseudo-)labels. Our approach leverages multiple instance learning (MIL) and learning from label proportions (LLP) techniques in conjunction with prior information (e.g., document-sentence cosine similarity) to train a specialized model for sentence-level scoring. We also employ techniques which use model predictions to pseudo-label the train-set at the sentence-level for model training to further improve performance. We conduct extensive evaluations of our methods across six datasets and four tasks: retrieval, question answering, summarization, and math reasoning. Our results demonstrate improved performance compared to multiple baselines across most of these tasks. Our work is the first to develop response-level feedback to sentence-level scoring techniques, leveraging sentence-level prior information, along with comprehensive evaluations on multiple tasks as well as end-to-end finetuning evaluation showing performance comparable to a model trained on fine-grained human annotated labels.
In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.
This paper introduces MAD-MIL, a Multi-head Attention-based Deep Multiple Instance Learning model, designed for weakly supervised Whole Slide Images (WSIs) classification in digital pathology. Inspired by the multi-head attention mechanism of the Transformer, MAD-MIL simplifies model complexity while achieving competitive results against advanced models like CLAM and DS-MIL. Evaluated on the MNIST-BAGS and public datasets, including TUPAC16, TCGA BRCA, TCGA LUNG, and TCGA KIDNEY, MAD-MIL consistently outperforms ABMIL. This demonstrates enhanced information diversity, interpretability, and efficiency in slide representation. The model's effectiveness, coupled with fewer trainable parameters and lower computational complexity makes it a promising solution for automated pathology workflows. Our code is available at https://github.com/tueimage/MAD-MIL.
We propose MonoBox, an innovative box-supervised segmentation method constrained by monotonicity to liberate its training from the user-unfriendly box-tightness assumption. In contrast to conventional box-supervised segmentation, where the box edges must precisely touch the target boundaries, MonoBox leverages imprecisely-annotated boxes to achieve robust pixel-wise segmentation. The 'linchpin' is that, within the noisy zones around box edges, MonoBox discards the traditional misguiding multiple-instance learning loss, and instead optimizes a carefully-designed objective, termed monotonicity constraint. Along directions transitioning from the foreground to background, this new constraint steers responses to adhere to a trend of monotonically decreasing values. Consequently, the originally unreliable learning within the noisy zones is transformed into a correct and effective monotonicity optimization. Moreover, an adaptive label correction is introduced, enabling MonoBox to enhance the tightness of box annotations using predicted masks from the previous epoch and dynamically shrink the noisy zones as training progresses. We verify MonoBox in the box-supervised segmentation task of polyps, where satisfying box-tightness is challenging due to the vague boundaries between the polyp and normal tissues. Experiments on both public synthetic and in-house real noisy datasets demonstrate that MonoBox exceeds other anti-noise state-of-the-arts by improving Dice by at least 5.5% and 3.3%, respectively. Codes are at https://github.com/Huster-Hq/MonoBox.
Whole Slide Images (WSI), obtained by high-resolution digital scanning of microscope slides at multiple scales, are the cornerstone of modern Digital Pathology. However, they represent a particular challenge to AI-based/AI-mediated analysis because pathology labeling is typically done at slide-level, instead of tile-level. It is not just that medical diagnostics is recorded at the specimen level, the detection of oncogene mutation is also experimentally obtained, and recorded by initiatives like The Cancer Genome Atlas (TCGA), at the slide level. This configures a dual challenge: a) accurately predicting the overall cancer phenotype and b) finding out what cellular morphologies are associated with it at the tile level. To address these challenges, a weakly supervised Multiple Instance Learning (MIL) approach was explored for two prevalent cancer types, Invasive Breast Carcinoma (TCGA-BRCA) and Lung Squamous Cell Carcinoma (TCGA-LUSC). This approach was explored for tumor detection at low magnification levels and TP53 mutations at various levels. Our results show that a novel additive implementation of MIL matched the performance of reference implementation (AUC 0.96), and was only slightly outperformed by Attention MIL (AUC 0.97). More interestingly from the perspective of the molecular pathologist, these different AI architectures identify distinct sensitivities to morphological features (through the detection of Regions of Interest, RoI) at different amplification levels. Tellingly, TP53 mutation was most sensitive to features at the higher applications where cellular morphology is resolved.
In digital pathology, the multiple instance learning (MIL) strategy is widely used in the weakly supervised histopathology whole slide image (WSI) classification task where giga-pixel WSIs are only labeled at the slide level. However, existing attention-based MIL approaches often overlook contextual information and intrinsic spatial relationships between neighboring tissue tiles, while graph-based MIL frameworks have limited power to recognize the long-range dependencies. In this paper, we introduce the integrative graph-transformer framework that simultaneously captures the context-aware relational features and global WSI representations through a novel Graph Transformer Integration (GTI) block. Specifically, each GTI block consists of a Graph Convolutional Network (GCN) layer modeling neighboring relations at the local instance level and an efficient global attention model capturing comprehensive global information from extensive feature embeddings. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and BRIGHT, demonstrate the superiority of our approach over current state-of-the-art MIL methods, achieving an improvement of 1.0% to 2.6% in accuracy and 0.7%-1.6% in AUROC.
PURPOSE: Deep learning methods for classifying prostate cancer (PCa) in ultrasound images typically employ convolutional networks (CNNs) to detect cancer in small regions of interest (ROI) along a needle trace region. However, this approach suffers from weak labelling, since the ground-truth histopathology labels do not describe the properties of individual ROIs. Recently, multi-scale approaches have sought to mitigate this issue by combining the context awareness of transformers with a CNN feature extractor to detect cancer from multiple ROIs using multiple-instance learning (MIL). In this work, we present a detailed study of several image transformer architectures for both ROI-scale and multi-scale classification, and a comparison of the performance of CNNs and transformers for ultrasound-based prostate cancer classification. We also design a novel multi-objective learning strategy that combines both ROI and core predictions to further mitigate label noise. METHODS: We evaluate 3 image transformers on ROI-scale cancer classification, then use the strongest model to tune a multi-scale classifier with MIL. We train our MIL models using our novel multi-objective learning strategy and compare our results to existing baselines. RESULTS: We find that for both ROI-scale and multi-scale PCa detection, image transformer backbones lag behind their CNN counterparts. This deficit in performance is even more noticeable for larger models. When using multi-objective learning, we can improve performance of MIL, with a 77.9% AUROC, a sensitivity of 75.9%, and a specificity of 66.3%. CONCLUSION: Convolutional networks are better suited for modelling sparse datasets of prostate ultrasounds, producing more robust features than transformers in PCa detection. Multi-scale methods remain the best architecture for this task, with multi-objective learning presenting an effective way to improve performance.
Graph convolutional networks (GCNs) have emerged as a powerful alternative to multiple instance learning with convolutional neural networks in digital pathology, offering superior handling of structural information across various spatial ranges - a crucial aspect of learning from gigapixel H&E-stained whole slide images (WSI). However, graph message-passing algorithms often suffer from oversmoothing when aggregating a large neighborhood. Hence, effective modeling of multi-range interactions relies on the careful construction of the graph. Our proposed multi-scale GCN (MS-GCN) tackles this issue by leveraging information across multiple magnification levels in WSIs. MS-GCN enables the simultaneous modeling of long-range structural dependencies at lower magnifications and high-resolution cellular details at higher magnifications, akin to analysis pipelines usually conducted by pathologists. The architecture's unique configuration allows for the concurrent modeling of structural patterns at lower magnifications and detailed cellular features at higher ones, while also quantifying the contribution of each magnification level to the prediction. Through testing on different datasets, MS-GCN demonstrates superior performance over existing single-magnification GCN methods. The enhancement in performance and interpretability afforded by our method holds promise for advancing computational pathology models, especially in tasks requiring extensive spatial context.
Multiple Instance Learning (MIL) is a weakly supervised paradigm that has been successfully applied to many different scientific areas and is particularly well suited to medical imaging. Probabilistic MIL methods, and more specifically Gaussian Processes (GPs), have achieved excellent results due to their high expressiveness and uncertainty quantification capabilities. One of the most successful GP-based MIL methods, VGPMIL, resorts to a variational bound to handle the intractability of the logistic function. Here, we formulate VGPMIL using P\'olya-Gamma random variables. This approach yields the same variational posterior approximations as the original VGPMIL, which is a consequence of the two representations that the Hyperbolic Secant distribution admits. This leads us to propose a general GP-based MIL method that takes different forms by simply leveraging distributions other than the Hyperbolic Secant one. Using the Gamma distribution we arrive at a new approach that obtains competitive or superior predictive performance and efficiency. This is validated in a comprehensive experimental study including one synthetic MIL dataset, two well-known MIL benchmarks, and a real-world medical problem. We expect that this work provides useful ideas beyond MIL that can foster further research in the field.
In the realm of digital pathology, multi-magnification Multiple Instance Learning (multi-mag MIL) has proven effective in leveraging the hierarchical structure of Whole Slide Images (WSIs) to reduce information loss and redundant data. However, current methods fall short in bridging the domain gap between pretrained models and medical imaging, and often fail to account for spatial relationships across different magnifications. Addressing these challenges, we introduce the Concentric Dual Fusion Attention-MIL (CDFA-MIL) framework,which innovatively combines point-to-area feature-colum attention and point-to-point concentric-row attention using concentric patch. This approach is designed to effectively fuse correlated information, enhancing feature representation and providing stronger correlation guidance for WSI analysis. CDFA-MIL distinguishes itself by offering a robust fusion strategy that leads to superior WSI recognition. Its application has demonstrated exceptional performance, significantly surpassing existing MIL methods in accuracy and F1 scores on prominent datasets like Camelyon16 and TCGA-NSCLC. Specifically, CDFA-MIL achieved an average accuracy and F1-score of 93.7\% and 94.1\% respectively on these datasets, marking a notable advancement over traditional MIL approaches.