A Multi-scale Linear-time Encoder for Whole-Slide Image Analysis

We introduce Multi-scale Adaptive Recurrent Biomedical Linear-time Encoder (MARBLE), the first \textit{purely Mamba-based} multi-state multiple instance learning (MIL) framework for whole-slide image (WSI) analysis. MARBLE processes multiple magnification levels in parallel and integrates coarse-to-fine reasoning within a linear-time state-space model, efficiently capturing cross-scale dependencies with minimal parameter overhead. WSI analysis remains challenging due to gigapixel resolutions and hierarchical magnifications, while existing MIL methods typically operate at a single scale and transformer-based approaches suffer from quadratic attention costs. By coupling parallel multi-scale processing with linear-time sequence modeling, MARBLE provides a scalable and modular alternative to attention-based architectures. Experiments on five public datasets show improvements of up to \textbf{6.9\%} in AUC, \textbf{20.3\%} in accuracy, and \textbf{2.3\%} in C-index, establishing MARBLE as an efficient and generalizable framework for multi-scale WSI analysis.

Weak-to-Strong Generalization Enables Fully Automated De Novo Training of Multi-head Mask-RCNN Model for Segmenting Densely Overlapping Cell Nuclei in Multiplex Whole-slice Brain Images

We present a weak to strong generalization methodology for fully automated training of a multi-head extension of the Mask-RCNN method with efficient channel attention for reliable segmentation of overlapping cell nuclei in multiplex cyclic immunofluorescent (IF) whole-slide images (WSI), and present evidence for pseudo-label correction and coverage expansion, the key phenomena underlying weak to strong generalization. This method can learn to segment de novo a new class of images from a new instrument and/or a new imaging protocol without the need for human annotations. We also present metrics for automated self-diagnosis of segmentation quality in production environments, where human visual proofreading of massive WSI images is unaffordable. Our method was benchmarked against five current widely used methods and showed a significant improvement. The code, sample WSI images, and high-resolution segmentation results are provided in open form for community adoption and adaptation.

mViSE: A Visual Search Engine for Analyzing Multiplex IHC Brain Tissue Images

Whole-slide multiplex imaging of brain tissue generates massive information-dense images that are challenging to analyze and require custom software. We present an alternative query-driven programming-free strategy using a multiplex visual search engine (mViSE) that learns the multifaceted brain tissue chemoarchitecture, cytoarchitecture, and myeloarchitecture. Our divide-and-conquer strategy organizes the data into panels of related molecular markers and uses self-supervised learning to train a multiplex encoder for each panel with explicit visual confirmation of successful learning. Multiple panels can be combined to process visual queries for retrieving similar communities of individual cells or multicellular niches using information-theoretic methods. The retrievals can be used for diverse purposes including tissue exploration, delineating brain regions and cortical cell layers, profiling and comparing brain regions without computer programming. We validated mViSE's ability to retrieve single cells, proximal cell pairs, tissue patches, delineate cortical layers, brain regions and sub-regions. mViSE is provided as an open-source QuPath plug-in.

ConStruct: Structural Distillation of Foundation Models for Prototype-Based Weakly Supervised Histopathology Segmentation

Weakly supervised semantic segmentation (WSSS) in histopathology relies heavily on classification backbones, yet these models often localize only the most discriminative regions and struggle to capture the full spatial extent of tissue structures. Vision-language models such as CONCH offer rich semantic alignment and morphology-aware representations, while modern segmentation backbones like SegFormer preserve fine-grained spatial cues. However, combining these complementary strengths remains challenging, especially under weak supervision and without dense annotations. We propose a prototype learning framework for WSSS in histopathological images that integrates morphology-aware representations from CONCH, multi-scale structural cues from SegFormer, and text-guided semantic alignment to produce prototypes that are simultaneously semantically discriminative and spatially coherent. To effectively leverage these heterogeneous sources, we introduce text-guided prototype initialization that incorporates pathology descriptions to generate more complete and semantically accurate pseudo-masks. A structural distillation mechanism transfers spatial knowledge from SegFormer to preserve fine-grained morphological patterns and local tissue boundaries during prototype learning. Our approach produces high-quality pseudo masks without pixel-level annotations, improves localization completeness, and enhances semantic consistency across tissue types. Experiments on BCSS-WSSS datasets demonstrate that our prototype learning framework outperforms existing WSSS methods while remaining computationally efficient through frozen foundation model backbones and lightweight trainable adapters.

DualProtoSeg: Simple and Efficient Design with Text- and Image-Guided Prototype Learning for Weakly Supervised Histopathology Image Segmentation

Weakly supervised semantic segmentation (WSSS) in histopathology seeks to reduce annotation cost by learning from image-level labels, yet it remains limited by inter-class homogeneity, intra-class heterogeneity, and the region-shrinkage effect of CAM-based supervision. We propose a simple and effective prototype-driven framework that leverages vision-language alignment to improve region discovery under weak supervision. Our method integrates CoOp-style learnable prompt tuning to generate text-based prototypes and combines them with learnable image prototypes, forming a dual-modal prototype bank that captures both semantic and appearance cues. To address oversmoothing in ViT representations, we incorporate a multi-scale pyramid module that enhances spatial precision and improves localization quality. Experiments on the BCSS-WSSS benchmark show that our approach surpasses existing state-of-the-art methods, and detailed analyses demonstrate the benefits of text description diversity, context length, and the complementary behavior of text and image prototypes. These results highlight the effectiveness of jointly leveraging textual semantics and visual prototype learning for WSSS in digital pathology.

Contrastive Integrated Gradients: A Feature Attribution-Based Method for Explaining Whole Slide Image Classification

Interpretability is essential in Whole Slide Image (WSI) analysis for computational pathology, where understanding model predictions helps build trust in AI-assisted diagnostics. While Integrated Gradients (IG) and related attribution methods have shown promise, applying them directly to WSIs introduces challenges due to their high-resolution nature. These methods capture model decision patterns but may overlook class-discriminative signals that are crucial for distinguishing between tumor subtypes. In this work, we introduce Contrastive Integrated Gradients (CIG), a novel attribution method that enhances interpretability by computing contrastive gradients in logit space. First, CIG highlights class-discriminative regions by comparing feature importance relative to a reference class, offering sharper differentiation between tumor and non-tumor areas. Second, CIG satisfies the axioms of integrated attribution, ensuring consistency and theoretical soundness. Third, we propose two attribution quality metrics, MIL-AIC and MIL-SIC, which measure how predictive information and model confidence evolve with access to salient regions, particularly under weak supervision. We validate CIG across three datasets spanning distinct cancer types: CAMELYON16 (breast cancer metastasis in lymph nodes), TCGA-RCC (renal cell carcinoma), and TCGA-Lung (lung cancer). Experimental results demonstrate that CIG yields more informative attributions both quantitatively, using MIL-AIC and MIL-SIC, and qualitatively, through visualizations that align closely with ground truth tumor regions, underscoring its potential for interpretable and trustworthy WSI-based diagnostics

Interpreting Radiologist's Intention from Eye Movements in Chest X-ray Diagnosis

Radiologists rely on eye movements to navigate and interpret medical images. A trained radiologist possesses knowledge about the potential diseases that may be present in the images and, when searching, follows a mental checklist to locate them using their gaze. This is a key observation, yet existing models fail to capture the underlying intent behind each fixation. In this paper, we introduce a deep learning-based approach, RadGazeIntent, designed to model this behavior: having an intention to find something and actively searching for it. Our transformer-based architecture processes both the temporal and spatial dimensions of gaze data, transforming fine-grained fixation features into coarse, meaningful representations of diagnostic intent to interpret radiologists' goals. To capture the nuances of radiologists' varied intention-driven behaviors, we process existing medical eye-tracking datasets to create three intention-labeled subsets: RadSeq (Systematic Sequential Search), RadExplore (Uncertainty-driven Exploration), and RadHybrid (Hybrid Pattern). Experimental results demonstrate RadGazeIntent's ability to predict which findings radiologists are examining at specific moments, outperforming baseline methods across all intention-labeled datasets.

Beyond the First Read: AI-Assisted Perceptual Error Detection in Chest Radiography Accounting for Interobserver Variability

Chest radiography is widely used in diagnostic imaging. However, perceptual errors -- especially overlooked but visible abnormalities -- remain common and clinically significant. Current workflows and AI systems provide limited support for detecting such errors after interpretation and often lack meaningful human--AI collaboration. We introduce RADAR (Radiologist--AI Diagnostic Assistance and Review), a post-interpretation companion system. RADAR ingests finalized radiologist annotations and CXR images, then performs regional-level analysis to detect and refer potentially missed abnormal regions. The system supports a "second-look" workflow and offers suggested regions of interest (ROIs) rather than fixed labels to accommodate inter-observer variation. We evaluated RADAR on a simulated perceptual-error dataset derived from de-identified CXR cases, using F1 score and Intersection over Union (IoU) as primary metrics. RADAR achieved a recall of 0.78, precision of 0.44, and an F1 score of 0.56 in detecting missed abnormalities in the simulated perceptual-error dataset. Although precision is moderate, this reduces over-reliance on AI by encouraging radiologist oversight in human--AI collaboration. The median IoU was 0.78, with more than 90% of referrals exceeding 0.5 IoU, indicating accurate regional localization. RADAR effectively complements radiologist judgment, providing valuable post-read support for perceptual-error detection in CXR interpretation. Its flexible ROI suggestions and non-intrusive integration position it as a promising tool in real-world radiology workflows. To facilitate reproducibility and further evaluation, we release a fully open-source web implementation alongside a simulated error dataset. All code, data, demonstration videos, and the application are publicly available at https://github.com/avutukuri01/RADAR.

Multimodal Learning and Cognitive Processes in Radiology: MedGaze for Chest X-ray Scanpath Prediction

Predicting human gaze behavior within computer vision is integral for developing interactive systems that can anticipate user attention, address fundamental questions in cognitive science, and hold implications for fields like human-computer interaction (HCI) and augmented/virtual reality (AR/VR) systems. Despite methodologies introduced for modeling human eye gaze behavior, applying these models to medical imaging for scanpath prediction remains unexplored. Our proposed system aims to predict eye gaze sequences from radiology reports and CXR images, potentially streamlining data collection and enhancing AI systems using larger datasets. However, predicting human scanpaths on medical images presents unique challenges due to the diverse nature of abnormal regions. Our model predicts fixation coordinates and durations critical for medical scanpath prediction, outperforming existing models in the computer vision community. Utilizing a two-stage training process and large publicly available datasets, our approach generates static heatmaps and eye gaze videos aligned with radiology reports, facilitating comprehensive analysis. We validate our approach by comparing its performance with state-of-the-art methods and assessing its generalizability among different radiologists, introducing novel strategies to model radiologists' search patterns during CXR image diagnosis. Based on the radiologist's evaluation, MedGaze can generate human-like gaze sequences with a high focus on relevant regions over the CXR images. It sometimes also outperforms humans in terms of redundancy and randomness in the scanpaths.

Enhancing Radiological Diagnosis: A Collaborative Approach Integrating AI and Human Expertise for Visual Miss Correction

Human-AI collaboration to identify and correct perceptual errors in chest radiographs has not been previously explored. This study aimed to develop a collaborative AI system, CoRaX, which integrates eye gaze data and radiology reports to enhance diagnostic accuracy in chest radiology by pinpointing perceptual errors and refining the decision-making process. Using public datasets REFLACX and EGD-CXR, the study retrospectively developed CoRaX, employing a large multimodal model to analyze image embeddings, eye gaze data, and radiology reports. The system's effectiveness was evaluated based on its referral-making process, the quality of referrals, and performance in collaborative diagnostic settings. CoRaX was tested on a simulated error dataset of 271 samples with 28% (93 of 332) missed abnormalities. The system corrected 21% (71 of 332) of these errors, leaving 7% (22 of 312) unresolved. The Referral-Usefulness score, indicating the accuracy of predicted regions for all true referrals, was 0.63 (95% CI 0.59, 0.68). The Total-Usefulness score, reflecting the diagnostic accuracy of CoRaX's interactions with radiologists, showed that 84% (237 of 280) of these interactions had a score above 0.40. In conclusion, CoRaX efficiently collaborates with radiologists to address perceptual errors across various abnormalities, with potential applications in the education and training of novice radiologists.