Integrative Graph-Transformer Framework for Histopathology Whole Slide Image Representation and Classification

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.

Multimodal wearable EEG, EMG and accelerometry measurements improve the accuracy of tonic-clonic seizure detection in-hospital

Objective: Most current wearable tonic-clonic seizure (TCS) detection systems are based on extra-cerebral signals, such as electromyography (EMG) or accelerometry (ACC). Although many of these devices show good sensitivity in seizure detection, their false positive rates (FPR) are still relatively high. Wearable EEG may improve performance; however, studies investigating this remain scarce. This paper aims 1) to investigate the possibility of detecting TCSs with a behind-the-ear, two-channel wearable EEG, and 2) to evaluate the added value of wearable EEG to other non-EEG modalities in multimodal TCS detection. Method: We included 27 participants with a total of 44 TCSs from the European multicenter study SeizeIT2. The multimodal wearable detection system Sensor Dot (Byteflies) was used to measure two-channel, behind-the-ear EEG, EMG, electrocardiography (ECG), ACC and gyroscope (GYR). First, we evaluated automatic unimodal detection of TCSs, using performance metrics such as sensitivity, precision, FPR and F1-score. Secondly, we fused the different modalities and again assessed performance. Algorithm-labeled segments were then provided to a neurologist and a wearable data expert, who reviewed and annotated the true positive TCSs, and discarded false positives (FPs). Results: Wearable EEG outperformed the other modalities in unimodal TCS detection by achieving a sensitivity of 100.0% and a FPR of 10.3/24h (compared to 97.7% sensitivity and 30.9/24h FPR for EMG; 95.5% sensitivity and 13.9 FPR for ACC). The combination of wearable EEG and EMG achieved overall the most clinically useful performance in offline TCS detection with a sensitivity of 97.7%, a FPR of 0.4/24 h, a precision of 43.0%, and a F1-score of 59.7%. Subsequent visual review of the automated detections resulted in maximal sensitivity and zero FPs.

An Interpretable Evaluation of Entropy-based Novelty of Generative Models

The massive developments of generative model frameworks and architectures require principled methods for the evaluation of a model's novelty compared to a reference dataset or baseline generative models. While the recent literature has extensively studied the evaluation of the quality, diversity, and generalizability of generative models, the assessment of a model's novelty compared to a baseline model has not been adequately studied in the machine learning community. In this work, we focus on the novelty assessment under multi-modal generative models and attempt to answer the following question: Given the samples of a generative model $\mathcal{G}$ and a reference dataset $\mathcal{S}$, how can we discover and count the modes expressed by $\mathcal{G}$ more frequently than in $\mathcal{S}$. We introduce a spectral approach to the described task and propose the Kernel-based Entropic Novelty (KEN) score to quantify the mode-based novelty of distribution $P_\mathcal{G}$ with respect to distribution $P_\mathcal{S}$. We analytically interpret the behavior of the KEN score under mixture distributions with sub-Gaussian components. Next, we develop a method based on Cholesky decomposition to compute the KEN score from observed samples. We support the KEN-based quantification of novelty by presenting several numerical results on synthetic and real image distributions. Our numerical results indicate the success of the proposed approach in detecting the novel modes and the comparison of state-of-the-art generative models.

Genie: Generative Interactive Environments

We introduce Genie, the first generative interactive environment trained in an unsupervised manner from unlabelled Internet videos. The model can be prompted to generate an endless variety of action-controllable virtual worlds described through text, synthetic images, photographs, and even sketches. At 11B parameters, Genie can be considered a foundation world model. It is comprised of a spatiotemporal video tokenizer, an autoregressive dynamics model, and a simple and scalable latent action model. Genie enables users to act in the generated environments on a frame-by-frame basis despite training without any ground-truth action labels or other domain-specific requirements typically found in the world model literature. Further the resulting learned latent action space facilitates training agents to imitate behaviors from unseen videos, opening the path for training generalist agents of the future.

Offline Actor-Critic Reinforcement Learning Scales to Large Models

We show that offline actor-critic reinforcement learning can scale to large models - such as transformers - and follows similar scaling laws as supervised learning. We find that offline actor-critic algorithms can outperform strong, supervised, behavioral cloning baselines for multi-task training on a large dataset containing both sub-optimal and expert behavior on 132 continuous control tasks. We introduce a Perceiver-based actor-critic model and elucidate the key model features needed to make offline RL work with self- and cross-attention modules. Overall, we find that: i) simple offline actor critic algorithms are a natural choice for gradually moving away from the currently predominant paradigm of behavioral cloning, and ii) via offline RL it is possible to learn multi-task policies that master many domains simultaneously, including real robotics tasks, from sub-optimal demonstrations or self-generated data.

SI-MIL: Taming Deep MIL for Self-Interpretability in Gigapixel Histopathology

Introducing interpretability and reasoning into Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) analysis is challenging, given the complexity of gigapixel slides. Traditionally, MIL interpretability is limited to identifying salient regions deemed pertinent for downstream tasks, offering little insight to the end-user (pathologist) regarding the rationale behind these selections. To address this, we propose Self-Interpretable MIL (SI-MIL), a method intrinsically designed for interpretability from the very outset. SI-MIL employs a deep MIL framework to guide an interpretable branch grounded on handcrafted pathological features, facilitating linear predictions. Beyond identifying salient regions, SI-MIL uniquely provides feature-level interpretations rooted in pathological insights for WSIs. Notably, SI-MIL, with its linear prediction constraints, challenges the prevalent myth of an inevitable trade-off between model interpretability and performance, demonstrating competitive results compared to state-of-the-art methods on WSI-level prediction tasks across three cancer types. In addition, we thoroughly benchmark the local- and global-interpretability of SI-MIL in terms of statistical analysis, a domain expert study, and desiderata of interpretability, namely, user-friendliness and faithfulness.

Mastering Stacking of Diverse Shapes with Large-Scale Iterative Reinforcement Learning on Real Robots

Reinforcement learning solely from an agent's self-generated data is often believed to be infeasible for learning on real robots, due to the amount of data needed. However, if done right, agents learning from real data can be surprisingly efficient through re-using previously collected sub-optimal data. In this paper we demonstrate how the increased understanding of off-policy learning methods and their embedding in an iterative online/offline scheme (``collect and infer'') can drastically improve data-efficiency by using all the collected experience, which empowers learning from real robot experience only. Moreover, the resulting policy improves significantly over the state of the art on a recently proposed real robot manipulation benchmark. Our approach learns end-to-end, directly from pixels, and does not rely on additional human domain knowledge such as a simulator or demonstrations.

Equivariant Data Augmentation for Generalization in Offline Reinforcement Learning

We present a novel approach to address the challenge of generalization in offline reinforcement learning (RL), where the agent learns from a fixed dataset without any additional interaction with the environment. Specifically, we aim to improve the agent's ability to generalize to out-of-distribution goals. To achieve this, we propose to learn a dynamics model and check if it is equivariant with respect to a fixed type of transformation, namely translations in the state space. We then use an entropy regularizer to increase the equivariant set and augment the dataset with the resulting transformed samples. Finally, we learn a new policy offline based on the augmented dataset, with an off-the-shelf offline RL algorithm. Our experimental results demonstrate that our approach can greatly improve the test performance of the policy on the considered environments.

Attention De-sparsification Matters: Inducing Diversity in Digital Pathology Representation Learning

We propose DiRL, a Diversity-inducing Representation Learning technique for histopathology imaging. Self-supervised learning techniques, such as contrastive and non-contrastive approaches, have been shown to learn rich and effective representations of digitized tissue samples with limited pathologist supervision. Our analysis of vanilla SSL-pretrained models' attention distribution reveals an insightful observation: sparsity in attention, i.e, models tends to localize most of their attention to some prominent patterns in the image. Although attention sparsity can be beneficial in natural images due to these prominent patterns being the object of interest itself, this can be sub-optimal in digital pathology; this is because, unlike natural images, digital pathology scans are not object-centric, but rather a complex phenotype of various spatially intermixed biological components. Inadequate diversification of attention in these complex images could result in crucial information loss. To address this, we leverage cell segmentation to densely extract multiple histopathology-specific representations, and then propose a prior-guided dense pretext task for SSL, designed to match the multiple corresponding representations between the views. Through this, the model learns to attend to various components more closely and evenly, thus inducing adequate diversification in attention for capturing context rich representations. Through quantitative and qualitative analysis on multiple tasks across cancer types, we demonstrate the efficacy of our method and observe that the attention is more globally distributed.

SAM-Path: A Segment Anything Model for Semantic Segmentation in Digital Pathology

Semantic segmentations of pathological entities have crucial clinical value in computational pathology workflows. Foundation models, such as the Segment Anything Model (SAM), have been recently proposed for universal use in segmentation tasks. SAM shows remarkable promise in instance segmentation on natural images. However, the applicability of SAM to computational pathology tasks is limited due to the following factors: (1) lack of comprehensive pathology datasets used in SAM training and (2) the design of SAM is not inherently optimized for semantic segmentation tasks. In this work, we adapt SAM for semantic segmentation by introducing trainable class prompts, followed by further enhancements through the incorporation of a pathology encoder, specifically a pathology foundation model. Our framework, SAM-Path enhances SAM's ability to conduct semantic segmentation in digital pathology without human input prompts. Through experiments on two public pathology datasets, the BCSS and the CRAG datasets, we demonstrate that the fine-tuning with trainable class prompts outperforms vanilla SAM with manual prompts and post-processing by 27.52% in Dice score and 71.63% in IOU. On these two datasets, the proposed additional pathology foundation model further achieves a relative improvement of 5.07% to 5.12% in Dice score and 4.50% to 8.48% in IOU.