Whole Slide Image (WSI) analysis is a powerful method to facilitate the diagnosis of cancer in tissue samples. Automating this diagnosis poses various issues, most notably caused by the immense image resolution and limited annotations. WSIs commonly exhibit resolutions of 100Kx100K pixels. Annotating cancerous areas in WSIs on the pixel level is prohibitively labor-intensive and requires a high level of expert knowledge. Multiple instance learning (MIL) alleviates the need for expensive pixel-level annotations. In MIL, learning is performed on slide-level labels, in which a pathologist provides information about whether a slide includes cancerous tissue. Here, we propose Self-ViT-MIL, a novel approach for classifying and localizing cancerous areas based on slide-level annotations, eliminating the need for pixel-wise annotated training data. Self-ViT- MIL is pre-trained in a self-supervised setting to learn rich feature representation without relying on any labels. The recent Vision Transformer (ViT) architecture builds the feature extractor of Self-ViT-MIL. For localizing cancerous regions, a MIL aggregator with global attention is utilized. To the best of our knowledge, Self-ViT- MIL is the first approach to introduce self-supervised ViTs in MIL-based WSI analysis tasks. We showcase the effectiveness of our approach on the common Camelyon16 dataset. Self-ViT-MIL surpasses existing state-of-the-art MIL-based approaches in terms of accuracy and area under the curve (AUC).
Current weakly supervised video anomaly detection algorithms mostly use multiple instance learning (MIL) or their varieties. Almost all recent approaches focus on how to select the correct snippets for training to improve the performance. They overlook or do not realize the power of video classification in boosting the performance of anomaly detection. In this paper, we study explicitly the power of video classification supervision using a BERT or LSTM. With this BERT or LSTM, CNN features of all snippets of a video can be aggregated into a single feature which can be used for video classification. This simple yet powerful video classification supervision, combined into the MIL framework, brings extraordinary performance improvement on all three major video anomaly detection datasets. Particularly it improves the mean average precision (mAP) on the XD-Violence from SOTA 78.84\% to new 82.10\%. The source code is available at https://github.com/wjtan99/BERT_Anomaly_Video_Classification.
Lesion appearance is a crucial clue for medical providers to distinguish referable diabetic retinopathy (rDR) from non-referable DR. Most existing large-scale DR datasets contain only image-level labels rather than pixel-based annotations. This motivates us to develop algorithms to classify rDR and segment lesions via image-level labels. This paper leverages self-supervised equivariant learning and attention-based multi-instance learning (MIL) to tackle this problem. MIL is an effective strategy to differentiate positive and negative instances, helping us discard background regions (negative instances) while localizing lesion regions (positive ones). However, MIL only provides coarse lesion localization and cannot distinguish lesions located across adjacent patches. Conversely, a self-supervised equivariant attention mechanism (SEAM) generates a segmentation-level class activation map (CAM) that can guide patch extraction of lesions more accurately. Our work aims at integrating both methods to improve rDR classification accuracy. We conduct extensive validation experiments on the Eyepacs dataset, achieving an area under the receiver operating characteristic curve (AU ROC) of 0.958, outperforming current state-of-the-art algorithms.
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.
Detecting anomalies over real-world datasets remains a challenging task. Data annotation is an intensive human labor problem, particularly in sequential datasets, where the start and end time of anomalies are not known. As a result, data collected from sequential real-world processes can be largely unlabeled or contain inaccurate labels. These characteristics challenge the application of anomaly detection techniques based on supervised learning. In contrast, Multiple Instance Learning (MIL) has been shown effective on problems with incomplete knowledge of labels in the training dataset, mainly due to the notion of bags. While largely under-leveraged for anomaly detection, MIL provides an appealing formulation for anomaly detection over real-world datasets, and it is the primary contribution of this paper. In this paper, we propose an MIL-based formulation and various algorithmic instantiations of this framework based on different design decisions for key components of the framework. We evaluate the resulting algorithms over four datasets that capture different physical processes along different modalities. The experimental evaluation draws out several observations. The MIL-based formulation performs no worse than single instance learning on easy to moderate datasets and outperforms single-instance learning on more challenging datasets. Altogether, the results show that the framework generalizes well over diverse datasets resulting from different real-world application domains.
We propose a lightweight and accurate method for detecting anomalies in videos. Existing methods used multiple-instance learning (MIL) to determine the normal/abnormal status of each segment of the video. Recent successful researches argue that it is important to learn the temporal relationships among segments to achieve high accuracy, instead of focusing on only a single segment. Therefore we analyzed the existing methods that have been successful in recent years, and found that while it is indeed important to learn all segments together, the temporal orders among them are irrelevant to achieving high accuracy. Based on this finding, we do not use the MIL framework, but instead propose a lightweight model with a self-attention mechanism to automatically extract features that are important for determining normal/abnormal from all input segments. As a result, our neural network model has 1.3\% of the number of parameters of the existing method. We evaluated the frame-level detection accuracy of our method on three benchmark datasets (UCF-Crime, ShanghaiTech, and XD-Violence) and demonstrate that our method can achieve the comparable or better accuracy than state-of-the-art methods.
Histology images with multi-gigapixel of resolution yield rich information for cancer diagnosis and prognosis. Most of the time, only slide-level label is available because pixel-wise annotation is labour intensive task. In this paper, we propose a deep learning pipeline for classification in histology images. Using multiple instance learning, we attempt to predict the latent membrane protein 1 (LMP1) status of nasopharyngeal carcinoma (NPC) based on haematoxylin and eosin-stain (H&E) histology images. We utilised attention mechanism with residual connection for our aggregation layers. In our 3-fold cross-validation experiment, we achieved average accuracy, AUC and F1-score 0.936, 0.995 and 0.862, respectively. This method also allows us to examine the model interpretability by visualising attention scores. To the best of our knowledge, this is the first attempt to predict LMP1 status on NPC using deep learning.
Current methods for text-to-video retrieval (T2VR) are trained and tested on video-captioning oriented datasets such as MSVD, MSR-VTT and VATEX. A key property of these datasets is that videos are assumed to be temporally pre-trimmed with short duration, whilst the provided captions well describe the gist of the video content. Consequently, for a given paired video and caption, the video is supposed to be fully relevant to the caption. In reality, however, as queries are not known a priori, pre-trimmed video clips may not contain sufficient content to fully meet the query. This suggests a gap between the literature and the real world. To fill the gap, we propose in this paper a novel T2VR subtask termed Partially Relevant Video Retrieval (PRVR). An untrimmed video is considered to be partially relevant w.r.t. a given textual query if it contains a moment relevant to the query. PRVR aims to retrieve such partially relevant videos from a large collection of untrimmed videos. PRVR differs from single video moment retrieval and video corpus moment retrieval, as the latter two are to retrieve moments rather than untrimmed videos. We formulate PRVR as a multiple instance learning (MIL) problem, where a video is simultaneously viewed as a bag of video clips and a bag of video frames. Clips and frames represent video content at different time scales. We propose a Multi-Scale Similarity Learning (MS-SL) network that jointly learns clip-scale and frame-scale similarities for PRVR. Extensive experiments on three datasets (TVR, ActivityNet Captions, and Charades-STA) demonstrate the viability of the proposed method. We also show that our method can be used for improving video corpus moment retrieval.
Open Set Video Anomaly Detection (OpenVAD) aims to identify abnormal events from video data where both known anomalies and novel ones exist in testing. Unsupervised models learned solely from normal videos are applicable to any testing anomalies but suffer from a high false positive rate. In contrast, weakly supervised methods are effective in detecting known anomalies but could fail in an open world. We develop a novel weakly supervised method for the OpenVAD problem by integrating evidential deep learning (EDL) and normalizing flows (NFs) into a multiple instance learning (MIL) framework. Specifically, we propose to use graph neural networks and triplet loss to learn discriminative features for training the EDL classifier, where the EDL is capable of identifying the unknown anomalies by quantifying the uncertainty. Moreover, we develop an uncertainty-aware selection strategy to obtain clean anomaly instances and a NFs module to generate the pseudo anomalies. Our method is superior to existing approaches by inheriting the advantages of both the unsupervised NFs and the weakly-supervised MIL framework. Experimental results on multiple real-world video datasets show the effectiveness of our method.
For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.
The presented first-of-its-kind study effectively identifies and visualizes the second-by-second pattern differences in the physiological arousal of preschool-age children who do stutter (CWS) and who do not stutter (CWNS) while speaking perceptually fluently in two challenging conditions i.e speaking in stressful situations and narration. The first condition may affect children's speech due to high arousal; the latter introduces linguistic, cognitive, and communicative demands on speakers. We collected physiological parameters data from 70 children in the two target conditions. First, we adopt a novel modality-wise multiple-instance-learning (MI-MIL) approach to classify CWS vs. CWNS in different conditions effectively. The evaluation of this classifier addresses four critical research questions that align with state-of-the-art speech science studies' interests. Later, we leverage SHAP classifier interpretations to visualize the salient, fine-grain, and temporal physiological parameters unique to CWS at the population/group-level and personalized-level. While group-level identification of distinct patterns would enhance our understanding of stuttering etiology and development, the personalized-level identification would enable remote, continuous, and real-time assessment of stuttering children's physiological arousal, which may lead to personalized, just-in-time interventions, resulting in an improvement in speech fluency. The presented MI-MIL approach is novel, generalizable to different domains, and real-time executable. Finally, comprehensive evaluations are done on multiple datasets, presented framework, and several baselines that identified notable insights on CWSs' physiological arousal during speech production.
Video anomaly detection is recently formulated as a multiple instance learning task under weak supervision, in which each video is treated as a bag of snippets to be determined whether contains anomalies. Previous efforts mainly focus on the discrimination of the snippet itself without modeling the temporal dynamics, which refers to the variation of adjacent snippets. Therefore, we propose a Discriminative Dynamics Learning (DDL) method with two objective functions, i.e., dynamics ranking loss and dynamics alignment loss. The former aims to enlarge the score dynamics gap between positive and negative bags while the latter performs temporal alignment of the feature dynamics and score dynamics within the bag. Moreover, a Locality-aware Attention Network (LA-Net) is constructed to capture global correlations and re-calibrate the location preference across snippets, followed by a multilayer perceptron with causal convolution to obtain anomaly scores. Experimental results show that our method achieves significant improvements on two challenging benchmarks, i.e., UCF-Crime and XD-Violence.
Early detection of cancers has been much explored due to its paramount importance in biomedical fields. Among different types of data used to answer this biological question, studies based on T cell receptors (TCRs) are under recent spotlight due to the growing appreciation of the roles of the host immunity system in tumor biology. However, the one-to-many correspondence between a patient and multiple TCR sequences hinders researchers from simply adopting classical statistical/machine learning methods. There were recent attempts to model this type of data in the context of multiple instance learning (MIL). Despite the novel application of MIL to cancer detection using TCR sequences and the demonstrated adequate performance in several tumor types, there is still room for improvement, especially for certain cancer types. Furthermore, explainable neural network models are not fully investigated for this application. In this article, we propose multiple instance neural networks based on sparse attention (MINN-SA) to enhance the performance in cancer detection and explainability. The sparse attention structure drops out uninformative instances in each bag, achieving both interpretability and better predictive performance in combination with the skip connection. Our experiments show that MINN-SA yields the highest area under the ROC curve (AUC) scores on average measured across 10 different types of cancers, compared to existing MIL approaches. Moreover, we observe from the estimated attentions that MINN-SA can identify the TCRs that are specific for tumor antigens in the same T cell repertoire.
Multiple instance learning (MIL) is a powerful approach to classify whole slide images (WSIs) for diagnostic pathology. A fundamental challenge of MIL on WSI classification is to discover the \textit{critical instances} that trigger the bag label. However, previous methods are primarily designed under the independent and identical distribution hypothesis (\textit{i.i.d}), ignoring either the correlations between instances or heterogeneity of tumours. In this paper, we propose a novel multiplex-detection-based multiple instance learning (MDMIL) to tackle the issues above. Specifically, MDMIL is constructed by the internal query generation module (IQGM) and the multiplex detection module (MDM) and assisted by the memory-based contrastive loss during training. Firstly, IQGM gives the probability of instances and generates the internal query (IQ) for the subsequent MDM by aggregating highly reliable features after the distribution analysis. Secondly, the multiplex-detection cross-attention (MDCA) and multi-head self-attention (MHSA) in MDM cooperate to generate the final representations for the WSI. In this process, the IQ and trainable variational query (VQ) successfully build up the connections between instances and significantly improve the model's robustness toward heterogeneous tumours. At last, to further enforce constraints in the feature space and stabilize the training process, we adopt a memory-based contrastive loss, which is practicable for WSI classification even with a single sample as input in each iteration. We conduct experiments on three computational pathology datasets, e.g., CAMELYON16, TCGA-NSCLC, and TCGA-RCC datasets. The superior accuracy and AUC demonstrate the superiority of our proposed MDMIL over other state-of-the-art methods.
Isoforms are mRNAs produced from the same gene site in the phenomenon called Alternative Splicing. Studies have shown that more than 95% of human multi-exon genes have undergone alternative splicing. Although there are few changes in mRNA sequence, They may have a systematic effect on cell function and regulation. It is widely reported that isoforms of a gene have distinct or even contrasting functions. Most studies have shown that alternative splicing plays a significant role in human health and disease. Despite the wide range of gene function studies, there is little information about isoforms' functionalities. Recently, some computational methods based on Multiple Instance Learning have been proposed to predict isoform function using gene function and gene expression profile. However, their performance is not desirable due to the lack of labeled training data. In addition, probabilistic models such as Conditional Random Field (CRF) have been used to model the relation between isoforms. This project uses all the data and valuable information such as isoform sequences, expression profiles, and gene ontology graphs and proposes a comprehensive model based on Deep Neural Networks. The UniProt Gene Ontology (GO) database is used as a standard reference for gene functions. The NCBI RefSeq database is used for extracting gene and isoform sequences, and the NCBI SRA database is used for expression profile data. Metrics such as Receiver Operating Characteristic Area Under the Curve (ROC AUC) and Precision-Recall Under the Curve (PR AUC) are used to measure the prediction accuracy.
Learning from raw data input, thus limiting the need for feature engineering, is a component of many successful applications of machine learning methods in various domains. While many problems naturally translate into a vector representation directly usable in standard classifiers, a number of data sources have the natural form of structured data interchange formats (e.g., security logs in JSON/XML format). Existing methods, such as in Hierarchical Multiple Instance Learning (HMIL), allow learning from such data in their raw form. However, the explanation of the classifiers trained on raw structured data remains largely unexplored. By treating these models as sub-set selections problems, we demonstrate how interpretable explanations, with favourable properties, can be generated using computationally efficient algorithms. We compare to an explanation technique adopted from graph neural networks showing an order of magnitude speed-up and higher-quality explanations.
The debate around the interpretability of attention mechanisms is centered on whether attention scores can be used as a proxy for the relative amounts of signal carried by sub-components of data. We propose to study the interpretability of attention in the context of set machine learning, where each data point is composed of an unordered collection of instances with a global label. For classical multiple-instance-learning problems and simple extensions, there is a well-defined "importance" ground truth that can be leveraged to cast interpretation as a binary classification problem, which we can quantitatively evaluate. By building synthetic datasets over several data modalities, we perform a systematic assessment of attention-based interpretations. We find that attention distributions are indeed often reflective of the relative importance of individual instances, but that silent failures happen where a model will have high classification performance but attention patterns that do not align with expectations. Based on these observations, we propose to use ensembling to minimize the risk of misleading attention-based explanations.
How to aggregate information from multiple instances is a key question multiple instance learning. Prior neural models implement different variants of the well-known encoder-decoder strategy according to which all input features are encoded a single, high-dimensional embedding which is then decoded to generate an output. In this work, inspired by Choquet capacities, we propose Capacity networks. Unlike encoder-decoders, Capacity networks generate multiple interpretable intermediate results which can be aggregated in a semantically meaningful space to obtain the final output. Our experiments show that implementing this simple inductive bias leads to improvements over different encoder-decoder architectures in a wide range of experiments. Moreover, the interpretable intermediate results make Capacity networks interpretable by design, which allows a semantically meaningful inspection, evaluation, and regularization of the network internals.
Learning accurate object detectors often requires large-scale training data with precise object bounding boxes. However, labeling such data is expensive and time-consuming. As the crowd-sourcing labeling process and the ambiguities of the objects may raise noisy bounding box annotations, the object detectors will suffer from the degenerated training data. In this work, we aim to address the challenge of learning robust object detectors with inaccurate bounding boxes. Inspired by the fact that localization precision suffers significantly from inaccurate bounding boxes while classification accuracy is less affected, we propose leveraging classification as a guidance signal for refining localization results. Specifically, by treating an object as a bag of instances, we introduce an Object-Aware Multiple Instance Learning approach (OA-MIL), featured with object-aware instance selection and object-aware instance extension. The former aims to select accurate instances for training, instead of directly using inaccurate box annotations. The latter focuses on generating high-quality instances for selection. Extensive experiments on synthetic noisy datasets (i.e., noisy PASCAL VOC and MS-COCO) and a real noisy wheat head dataset demonstrate the effectiveness of our OA-MIL. Code is available at https://github.com/cxliu0/OA-MIL.
Histopathology whole slide images (WSIs) play a very important role in clinical studies and serve as the gold standard for many cancer diagnoses. However, generating automatic tools for processing WSIs is challenging due to their enormous sizes. Currently, to deal with this issue, conventional methods rely on a multiple instance learning (MIL) strategy to process a WSI at patch level. Although effective, such methods are computationally expensive, because tiling a WSI into patches takes time and does not explore the spatial relations between these tiles. To tackle these limitations, we propose a locally supervised learning framework which processes the entire slide by exploring the entire local and global information that it contains. This framework divides a pre-trained network into several modules and optimizes each module locally using an auxiliary model. We also introduce a random feature reconstruction unit (RFR) to preserve distinguishing features during training and improve the performance of our method by 1% to 3%. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and LKS, highlight the superiority of our method on different classification tasks. Our method outperforms the state-of-the-art MIL methods by 2% to 5% in accuracy, while being 7 to 10 times faster. Additionally, when dividing it into eight modules, our method requires as little as 20% of the total gpu memory required by end-to-end training. Our code is available at https://github.com/cvlab-stonybrook/local_learning_wsi.