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Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's $κ$ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

High-fidelity registration of histopathological whole slide images (WSIs), such as hematoxylin & eosin (H&E) and immunohistochemistry (IHC), is vital for integrated molecular analysis but challenging to evaluate without ground-truth (GT) annotations. Existing WSI-level assessments -- using annotated landmarks or intensity-based similarity metrics -- are often time-consuming, unreliable, and computationally intensive, limiting large-scale applicability. This study proposes a fast, unsupervised framework that jointly employs down-sampled tissue masks- and deformations-based metrics for registration quality assessment (RQA) of registered H&E and IHC WSI pairs. The masks-based metrics measure global structural correspondence, while the deformations-based metrics evaluate local smoothness, continuity, and transformation realism. Validation across multiple IHC markers and multi-expert assessments demonstrate a strong correlation between automated metrics and human evaluations. In the absence of GT, this framework offers reliable, real-time RQA with high fidelity and minimal computational resources, making it suitable for large-scale quality control in digital pathology.

Automated radiology report drafting (ARRD) using vision-language models (VLMs) has advanced rapidly, yet most systems lack explicit uncertainty estimates, limiting trust and safe clinical deployment. We propose CONRep, a model-agnostic framework that integrates conformal prediction (CP) to provide statistically grounded uncertainty quantification for VLM-generated radiology reports. CONRep operates at both the label level, by calibrating binary predictions for predefined findings, and the sentence level, by assessing uncertainty in free-text impressions via image-text semantic alignment. We evaluate CONRep using both generative and contrastive VLMs on public chest X-ray datasets. Across both settings, outputs classified as high confidence consistently show significantly higher agreement with radiologist annotations and ground-truth impressions than low-confidence outputs. By enabling calibrated confidence stratification without modifying underlying models, CONRep improves the transparency, reliability, and clinical usability of automated radiology reporting systems.

Quantitative imaging methods, such as magnetic resonance fingerprinting (MRF), aim to extract interpretable pathology biomarkers by estimating biophysical tissue parameters from signal evolutions. However, the pattern-matching algorithms or neural networks used in such inverse problems often lack principled uncertainty quantification, which limits the trustworthiness and transparency, required for clinical acceptance. Here, we describe a physics-structured variational autoencoder (PS-VAE) designed for rapid extraction of voxelwise multi-parameter posterior distributions. Our approach integrates a differentiable spin physics simulator with self-supervised learning, and provides a full covariance that captures the inter-parameter correlations of the latent biophysical space. The method was validated in a multi-proton pool chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) molecular MRF study, across in-vitro phantoms, tumor-bearing mice, healthy human volunteers, and a subject with glioblastoma. The resulting multi-parametric posteriors are in good agreement with those calculated using a brute-force Bayesian analysis, while providing an orders-of-magnitude acceleration in whole brain quantification. In addition, we demonstrate how monitoring the multi-parameter posterior dynamics across progressively acquired signals provides practical insights for protocol optimization and may facilitate real-time adaptive acquisition.

Artificial intelligence (AI) has shown promise in detecting and characterizing musculoskeletal diseases from radiographs. However, most existing models remain task-specific, annotation-dependent, and limited in generalizability across diseases and anatomical regions. Although a generalizable foundation model trained on large-scale musculoskeletal radiographs is clinically needed, publicly available datasets remain limited in size and lack sufficient diversity to enable training across a wide range of musculoskeletal conditions and anatomical sites. Here, we present SKELEX, a large-scale foundation model for musculoskeletal radiographs, trained using self-supervised learning on 1.2 million diverse, condition-rich images. The model was evaluated on 12 downstream diagnostic tasks and generally outperformed baselines in fracture detection, osteoarthritis grading, and bone tumor classification. Furthermore, SKELEX demonstrated zero-shot abnormality localization, producing error maps that identified pathologic regions without task-specific training. Building on this capability, we developed an interpretable, region-guided model for predicting bone tumors, which maintained robust performance on independent external datasets and was deployed as a publicly accessible web application. Overall, SKELEX provides a scalable, label-efficient, and generalizable AI framework for musculoskeletal imaging, establishing a foundation for both clinical translation and data-efficient research in musculoskeletal radiology.

Temporal comparison of chest X-rays is fundamental to clinical radiology, enabling detection of disease progression, treatment response, and new findings. While vision-language models have advanced single-image report generation and visual grounding, no existing method combines these capabilities for temporal change detection. We introduce Temporal Radiology with Anatomical Change Explanation (TRACE), the first model that jointly performs temporal comparison, change classification, and spatial localization. Given a prior and current chest X-ray, TRACE generates natural language descriptions of interval changes (worsened, improved, stable) while grounding each finding with bounding box coordinates. TRACE demonstrates effective spatial localization with over 90% grounding accuracy, establishing a foundation for this challenging new task. Our ablation study uncovers an emergent capability: change detection arises only when temporal comparison and spatial grounding are jointly learned, as neither alone enables meaningful change detection. This finding suggests that grounding provides a spatial attention mechanism essential for temporal reasoning.

Deep learning based auto segmentation is increasingly used in radiotherapy, but conventional models often produce anatomically implausible false positives, or hallucinations, in slices lacking target structures. We propose a gated multi-head Transformer architecture based on Swin U-Net, augmented with inter-slice context integration and a parallel detection head, which jointly performs slice-level structure detection via a multi-layer perceptron and pixel-level segmentation through a context-enhanced stream. Detection outputs gate the segmentation predictions to suppress false positives in anatomically invalid slices, and training uses slice-wise Tversky loss to address class imbalance. Experiments on the Prostate-Anatomical-Edge-Cases dataset from The Cancer Imaging Archive demonstrate that the gated model substantially outperforms a non-gated segmentation-only baseline, achieving a mean Dice loss of $0.013 \pm 0.036$ versus $0.732 \pm 0.314$, with detection probabilities strongly correlated with anatomical presence, effectively eliminating spurious segmentations. In contrast, the non-gated model exhibited higher variability and persistent false positives across all slices. These results indicate that detection-based gating enhances robustness and anatomical plausibility in automated segmentation applications, reducing hallucinated predictions without compromising segmentation quality in valid slices, and offers a promising approach for improving the reliability of clinical radiotherapy auto-contouring workflows.

High-resolution spatial transcriptomics platforms, such as Xenium, generate single-cell images that capture both molecular and spatial context, but their extremely high dimensionality poses major challenges for representation learning and clustering. In this study, we analyze data from the Xenium platform, which captures high-resolution images of tumor microarray (TMA) tissues and converts them into cell-by-gene matrices suitable for computational analysis. We benchmark and extend nonnegative matrix factorization (NMF) for spatial transcriptomics by introducing two spatially regularized variants. First, we propose Spatial NMF (SNMF), a lightweight baseline that enforces local spatial smoothness by diffusing each cell's NMF factor vector over its spatial neighborhood. Second, we introduce Hybrid Spatial NMF (hSNMF), which performs spatially regularized NMF followed by Leiden clustering on a hybrid adjacency that integrates spatial proximity (via a contact-radius graph) and transcriptomic similarity through a tunable mixing parameter alpha. Evaluated on a cholangiocarcinoma dataset, SNMF and hSNMF achieve markedly improved spatial compactness (CHAOS < 0.004, Moran's I > 0.96), greater cluster separability (Silhouette > 0.12, DBI < 1.8), and higher biological coherence (CMC and enrichment) compared to other spatial baselines. Availability and implementation: https://github.com/ishtyaqmahmud/hSNMF

Accurate histopathologic interpretation is key for clinical decision-making; however, current deep learning models for digital pathology are often overconfident and poorly calibrated in out-of-distribution (OOD) settings, which limit trust and clinical adoption. Safety-critical medical imaging workflows benefit from intrinsic uncertainty-aware properties that can accurately reject OOD input. We implement the Spectral-normalized Neural Gaussian Process (SNGP), a set of lightweight modifications that apply spectral normalization and replace the final dense layer with a Gaussian process layer to improve single-model uncertainty estimation and OOD detection. We evaluate SNGP vs. deterministic and MonteCarlo dropout on six datasets across three biomedical classification tasks: white blood cells, amyloid plaques, and colorectal histopathology. SNGP has comparable in-distribution performance while significantly improving uncertainty estimation and OOD detection. Thus, SNGP or related models offer a useful framework for uncertainty-aware classification in digital pathology, supporting safe deployment and building trust with pathologists.

Drug-induced toxicity remains a leading cause of failure in preclinical development and early clinical trials. Detecting adverse effects at an early stage is critical to reduce attrition and accelerate the development of safe medicines. Histopathological evaluation remains the gold standard for toxicity assessment, but it relies heavily on expert pathologists, creating a bottleneck for large-scale screening. To address this challenge, we introduce an AI-based anomaly detection framework for histopathological whole-slide images (WSIs) in rodent livers from toxicology studies. The system identifies healthy tissue and known pathologies (anomalies) for which training data is available. In addition, it can detect rare pathologies without training data as out-of-distribution (OOD) findings. We generate a novel dataset of pixelwise annotations of healthy tissue and known pathologies and use this data to fine-tune a pre-trained Vision Transformer (DINOv2) via Low-Rank Adaptation (LoRA) in order to do tissue segmentation. Finally, we extract features for OOD detection using the Mahalanobis distance. To better account for class-dependent variability in histological data, we propose the use of class-specific thresholds. We optimize the thresholds using the mean of the false negative and false positive rates, resulting in only 0.16\% of pathological tissue classified as healthy and 0.35\% of healthy tissue classified as pathological. Applied to mouse liver WSIs with known toxicological findings, the framework accurately detects anomalies, including rare OOD morphologies. This work demonstrates the potential of AI-driven histopathology to support preclinical workflows, reduce late-stage failures, and improve efficiency in drug development.