ADR: Attention Diversification Regularization for Mitigating Overfitting in Multiple Instance Learning based Whole Slide Image Classification

Multiple Instance Learning (MIL) has demonstrated effectiveness in analyzing whole slide images (WSIs), yet it often encounters overfitting challenges in real-world applications. This paper reveals the correlation between MIL's performance and the entropy of attention values. Based on this observation, we propose Attention Diversity Regularization (ADR), a simple but effective technique aimed at promoting high entropy in attention values. Specifically, ADR introduces a negative Shannon entropy loss for attention values into the regular MIL framework. Compared to existing methods aimed at alleviating overfitting, which often necessitate additional modules or processing steps, our ADR approach requires no such extras, demonstrating simplicity and efficiency. We evaluate our ADR on three WSI classification tasks. ADR achieves superior performance over the state-of-the-art on most of them. We also show that ADR can enhance heatmaps, aligning them better with pathologists' diagnostic criteria. The source code is available at \url{https://github.com/dazhangyu123/ADR}.

LLMEmbed: Rethinking Lightweight LLM's Genuine Function in Text Classification

With the booming of Large Language Models (LLMs), prompt-learning has become a promising method mainly researched in various research areas. Recently, many attempts based on prompt-learning have been made to improve the performance of text classification. However, most of these methods are based on heuristic Chain-of-Thought (CoT), and tend to be more complex but less efficient. In this paper, we rethink the LLM-based text classification methodology, propose a simple and effective transfer learning strategy, namely LLMEmbed, to address this classical but challenging task. To illustrate, we first study how to properly extract and fuse the text embeddings via various lightweight LLMs at different network depths to improve their robustness and discrimination, then adapt such embeddings to train the classifier. We perform extensive experiments on publicly available datasets, and the results show that LLMEmbed achieves strong performance while enjoys low training overhead using lightweight LLM backbones compared to recent methods based on larger LLMs, i.e. GPT-3, and sophisticated prompt-based strategies. Our LLMEmbed achieves adequate accuracy on publicly available benchmarks without any fine-tuning while merely use 4% model parameters, 1.8% electricity consumption and 1.5% runtime compared to its counterparts. Code is available at: https://github.com/ChunLiu-cs/LLMEmbed-ACL2024.

Advancing Multimodal Medical Capabilities of Gemini

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

Achieving Near-Optimal Regret for Bandit Algorithms with Uniform Last-Iterate Guarantee

Existing performance measures for bandit algorithms such as regret, PAC bounds, or uniform-PAC (Dann et al., 2017), typically evaluate the cumulative performance, while allowing the play of an arbitrarily bad arm at any finite time t. Such a behavior can be highly detrimental in high-stakes applications. This paper introduces a stronger performance measure, the uniform last-iterate (ULI) guarantee, capturing both cumulative and instantaneous performance of bandit algorithms. Specifically, ULI characterizes the instantaneous performance since it ensures that the per-round regret of the played arm is bounded by a function, monotonically decreasing w.r.t. (large) round t, preventing revisits to bad arms when sufficient samples are available. We demonstrate that a near-optimal ULI guarantee directly implies near-optimal cumulative performance across aforementioned performance measures. To examine the achievability of ULI in the finite arm setting, we first provide two positive results that some elimination-based algorithms and high-probability adversarial algorithms with stronger analysis or additional designs, can attain near-optimal ULI guarantees. Then, we also provide a negative result, indicating that optimistic algorithms cannot achieve a near-optimal ULI guarantee. Finally, we propose an efficient algorithm for linear bandits with infinitely many arms, which achieves the ULI guarantee, given access to an optimization oracle.

PathMMU: A Massive Multimodal Expert-Level Benchmark for Understanding and Reasoning in Pathology

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for LMMs. It comprises 33,573 multimodal multi-choice questions and 21,599 images from various sources, and an explanation for the correct answer accompanies each question. The construction of PathMMU capitalizes on the robust capabilities of GPT-4V, utilizing approximately 30,000 gathered image-caption pairs to generate Q\&As. Significantly, to maximize PathMMU's authority, we invite six pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and three closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 51.7\% zero-shot performance, significantly lower than the 71.4\% demonstrated by human pathologists. After fine-tuning, even open-sourced LMMs can surpass GPT-4V with a performance of over 60\%, but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LLMs for pathology.

Benchmarking PathCLIP for Pathology Image Analysis

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pretraining (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, PathCLIP is specifically designed for pathology image analysis, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of Osteosarcoma and WSSS4LUAD. In our experiments, we introduce seven corruption types including brightness, contrast, Gaussian blur, resolution, saturation, hue, and markup at four severity levels. Through experiments, we find that PathCLIP is relatively robustness to image corruptions and surpasses OpenAI-CLIP and PLIP in zero-shot classification. Among the seven corruptions, blur and resolution can cause server performance degradation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-image retrieval, revealing that PathCLIP performs less effectively than PLIP on Osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it. We hope this study provides a qualitative impression of PathCLIP and helps understand its differences from other CLIP models.

Multi-modal Learning with Missing Modality in Predicting Axillary Lymph Node Metastasis

Multi-modal Learning has attracted widespread attention in medical image analysis. Using multi-modal data, whole slide images (WSIs) and clinical information, can improve the performance of deep learning models in the diagnosis of axillary lymph node metastasis. However, clinical information is not easy to collect in clinical practice due to privacy concerns, limited resources, lack of interoperability, etc. Although patient selection can ensure the training set to have multi-modal data for model development, missing modality of clinical information can appear during test. This normally leads to performance degradation, which limits the use of multi-modal models in the clinic. To alleviate this problem, we propose a bidirectional distillation framework consisting of a multi-modal branch and a single-modal branch. The single-modal branch acquires the complete multi-modal knowledge from the multi-modal branch, while the multi-modal learns the robust features of WSI from the single-modal. We conduct experiments on a public dataset of Lymph Node Metastasis in Early Breast Cancer to validate the method. Our approach not only achieves state-of-the-art performance with an AUC of 0.861 on the test set without missing data, but also yields an AUC of 0.842 when the rate of missing modality is 80\%. This shows the effectiveness of the approach in dealing with multi-modal data and missing modality. Such a model has the potential to improve treatment decision-making for early breast cancer patients who have axillary lymph node metastatic status.

Unleashing the Power of Prompt-driven Nucleus Instance Segmentation

Nuclear instance segmentation in histology images is crucial for a broad spectrum of clinical applications. Current prevailing nuclear instance segmentation algorithms rely on regression of nuclei contours, distance maps, watershed markers or a proxy nuclear representation of star-convex polygons. Consequently, these methods necessitate sophisticated post-processing operations to distinguish nuclei instances, which are commonly acknowledged to be error-prone and parameter-sensitive. Recently, the segment anything model (SAM) has earned attracted huge attention within the domain of medical image segmentation due to its impressive generalization ability and promptable property. Nevertheless, its potential on nuclear instance segmentation remains largely underexplored. In this paper, we present a novel prompt-driven framework that consists of a point prompter and a SAM for automatic nuclei instance segmentation. Specifically, the prompter learns to generate a unique point prompt for each nucleus while the SAM is fine tuned to output the corresponding mask of the cued nucleus. Furthermore, we propose to add adjacent nuclei as negative prompts to promote the model's ability to recognize overlapping nuclei. Without bells and whistles, our proposed method sets a new state-of-the-art performance on three challenging benchmarks. Our code is available at \textcolor{magenta}{\url{https://github.com/windygoo/PromptNucSeg}} .

MI-Gen: Multiple Instance Generation of Pathology Reports for Gigapixel Whole-Slide Images

Whole slide images are the foundation of digital pathology for the diagnosis and treatment of carcinomas. Writing pathology reports is laborious and error-prone for inexperienced pathologists. To reduce the workload and improve clinical automation, we investigate how to generate pathology reports given whole slide images. On the data end, we curated the largest WSI-text dataset (TCGA-PathoText). In specific, we collected nearly 10000 high-quality WSI-text pairs for visual-language models by recognizing and cleaning pathology reports which narrate diagnostic slides in TCGA. On the model end, we propose the multiple instance generative model (MI-Gen) which can produce pathology reports for gigapixel WSIs. We benchmark our model on the largest subset of TCGA-PathoText. Experimental results show our model can generate pathology reports which contain multiple clinical clues. Furthermore, WSI-text prediction can be seen as an approach of visual-language pre-training, which enables our model to be transferred to downstream diagnostic tasks like carcinoma grading and phenotyping. We observe that simple semantic extraction from the pathology reports can achieve the best performance (0.838 of F1 score) on BRCA subtyping without adding extra parameters or tricky fine-tuning. Our collected dataset and related code will all be publicly available.

Long-MIL: Scaling Long Contextual Multiple Instance Learning for Histopathology Whole Slide Image Analysis

Histopathology image analysis is the golden standard of clinical diagnosis for Cancers. In doctors daily routine and computer-aided diagnosis, the Whole Slide Image (WSI) of histopathology tissue is used for analysis. Because of the extremely large scale of resolution, previous methods generally divide the WSI into a large number of patches, then aggregate all patches within a WSI by Multi-Instance Learning (MIL) to make the slide-level prediction when developing computer-aided diagnosis tools. However, most previous WSI-MIL models using global-attention without pairwise interaction and any positional information, or self-attention with absolute position embedding can not well handle shape varying large WSIs, e.g. testing WSIs after model deployment may be larger than training WSIs, since the model development set is always limited due to the difficulty of histopathology WSIs collection. To deal with the problem, in this paper, we propose to amend position embedding for shape varying long-contextual WSI by introducing Linear Bias into Attention, and adapt it from 1-d long sequence into 2-d long-contextual WSI which helps model extrapolate position embedding to unseen or under-fitted positions. We further utilize Flash-Attention module to tackle the computational complexity of Transformer, which also keep full self-attention performance compared to previous attention approximation work. Our method, Long-contextual MIL (Long-MIL) are evaluated on extensive experiments including 4 dataset including WSI classification and survival prediction tasks to validate the superiority on shape varying WSIs. The source code will be open-accessed soon.