BenchX: Benchmarking AI Models for Cancer Detection and Localization with Demographic and Protocol Biases

Artificial intelligence (AI) has achieved remarkable success in medical imaging, but it is widely recognized that these models often perform inconsistently across real-world clinical settings. Such inconsistencies occur when patient demographics and imaging protocols vary, for example, in detecting small tumors, analyzing scans from different contrast phases, or evaluating patients of different ages or sexes. To quantify these inconsistencies, we develop a large-scale, open benchmark of 85,355 CT scans that systematically evaluates 12 tumor-detection AI models across tumor size, location, patient subgroup, and imaging protocol. We leverage large language models (LLMs) to extract and organize subgroup information from clinical data, which makes the analysis both scalable and reproducible. Our benchmark reveals that current state-of-the-art AI models, optimized for average accuracy, perform poorly in rare or underrepresented subgroups, such as young, female African Americans. However, collecting sufficient annotated data for these rare cases is often impractical. The benchmark provides a foundation for building more reliable and robust AI models for tumor detection and highlighting the need for rigorous, subgroup-level evaluation in medical imaging and computer vision. Datasets, code

Fast Voxelwise SNR Estimation for Iterative MRI Reconstructions

Purpose: To develop a fast, general-purpose framework for voxelwise noise characterization in linear and nonlinear iterative MRI reconstructions, recovering the image-domain noise variance from which SNR, $g$-factor, and related image-quality metrics are derived. The framework addresses both the intractability of closed-form formulas beyond Cartesian sampling and the long runtime of Pseudo Multiple Replica (PMR) methods. Methods: We propose PICO (Probing Image-space COvariance), an estimator that operates in the image domain by probing the image-domain noise covariance operator -- or, for nonlinear compressed-sensing reconstructions, the Jacobian of the converged solution -- with random probe images. Complex random-phase probes are shown theoretically and empirically to minimize estimator variance compared with Gaussian or real-valued alternatives. PICO was validated against analytical benchmarks and high-replica PMR references using retrospective Cartesian knee data ($R=2$), prospective non-Cartesian spiral brain phantom data ($R=2,3,4$), and compressed-sensing knee reconstructions ($R=2$). Results: In Cartesian experiments, PICO accurately reproduced analytical SENSE $g$-factor maps. In non-Cartesian spiral imaging ($R=2$), it achieved 1% estimation error in 64 s compared with 462 s for PMR (approximately 7.2x speedup), with the efficiency advantage persisting at higher acceleration. For nonlinear compressed sensing, the Jacobian-based estimator produced noise maps consistent with PMR while converging faster (52 s vs. 95 s; approximately 1.8x speedup). Conclusion: PICO provides a computationally efficient alternative to PMR for voxelwise noise and $g$-factor estimation across generalized iterative MRI reconstructions. By reusing existing reconstruction primitives, it enables voxelwise noise maps to be produced as a routine by-product of the reconstruction pipeline.

A Reasoning-Enabled Vision-Language Foundation Model for Chest X-ray Interpretation

Chest X-rays (CXRs) are among the most frequently performed imaging examinations worldwide, yet rising imaging volumes increase radiologist workload and the risk of diagnostic errors. Although artificial intelligence (AI) systems have shown promise for CXR interpretation, most generate only final predictions, without making explicit how visual evidence is translated into radiographic findings and diagnostic predictions. We present CheXOne, a reasoning-enabled vision-language model for CXR interpretation. CheXOne jointly generates diagnostic predictions and explicit, clinically grounded reasoning traces that connect visual evidence, radiographic findings, and these predictions. The model is trained on 14.7 million instruction and reasoning samples curated from 30 public datasets spanning 36 CXR interpretation tasks, using a two-stage framework that combines instruction tuning with reinforcement learning to improve reasoning quality. We evaluate CheXOne in zero-shot settings across visual question answering, report generation, visual grounding and reasoning assessment, covering 17 evaluation settings. CheXOne outperforms existing medical and general-domain foundation models and achieves strong performance on independent public benchmarks. A clinical reader study demonstrates that CheXOne-drafted reports are comparable to or better than resident-written reports in 55% of cases, while effectively addressing clinical indications and enhancing both report writing and CXR interpretation efficiency. Further analyses involving radiologists reveal that the generated reasoning traces show high clinical factuality and provide causal support for the final predictions, offering a plausible explanation for the performance gains. These results suggest that explicit reasoning can improve model performance, interpretability and clinical utility in AI-assisted CXR interpretation.

Clinician input steers frontier AI models toward both accurate and harmful decisions

Large language models (LLMs) are entering clinician workflows, yet evaluations rarely measure how clinician reasoning shapes model behavior during clinical interactions. We combined 61 New England Journal of Medicine Case Records with 92 real-world clinician-AI interactions to evaluate 21 reasoning LLM variants across 8 frontier models on differential diagnosis generation and next step recommendations under three conditions: reasoning alone, after expert clinician context, and after adversarial clinician context. LLM-clinician concordance increased substantially after clinician exposure, with simulations sharing >=3 differential diagnosis items rising from 65.8% to 93.5% and >=3 next step recommendations from 20.3% to 53.8%. Expert context significantly improved correct final diagnosis inclusion across all 21 models (mean +20.4 percentage points), reflecting both reasoning improvement and passive content echoing, while adversarial context caused significant diagnostic degradation in 14 models (mean -5.4 percentage points). Multi-turn disagreement probes revealed distinct model phenotypes ranging from highly conformist to dogmatic, with adversarial arguments remaining a persistent vulnerability even for otherwise resilient models. Inference-time scaling reduced harmful echoing of clinician-introduced recommendations across WHO-defined harm severity tiers (relative reductions: 62.7% mild, 57.9% moderate, 76.3% severe, 83.5% death-tier). In GPT-4o experiments, explicit clinician uncertainty signals improved diagnostic performance after adversarial context (final diagnosis inclusion 27% to 42%) and reduced alignment with incorrect arguments by 21%. These findings establish a foundation for evaluating clinician-AI collaboration, introducing interactive metrics and mitigation strategies essential for safety and robustness.

A data- and compute-efficient chest X-ray foundation model beyond aggressive scaling

Foundation models for medical imaging are typically pretrained on increasingly large datasets, following a "scale-at-all-costs" paradigm. However, this strategy faces two critical challenges: large-scale medical datasets often contain substantial redundancy and severe class imbalance that bias representation learning toward over-represented patterns, and indiscriminate training regardless of heterogeneity in data quality incurs considerable computational inefficiency. Here we demonstrate that active, principled data curation during pretraining can serve as a viable, cost-effective alternative to brute-force dataset enlargement. We introduce CheXficient, a chest X-ray (CXR) foundation model that selectively prioritizes informative training samples. CheXficient is pretrained on only 22.7% of 1,235,004 paired CXR images and reports while consuming under 27.3% of the total compute budget, yet achieving comparable or superior performance to its full-data counterpart and other large-scale pretrained models. We assess CheXficient across 20 individual benchmarks spanning 5 task types, including non-adapted off-the-shelf evaluations (zero-shot findings classification and crossmodal retrieval) and adapted downstream tasks (disease prediction, semantic segmentation, and radiology report generation). Further analyses show that CheXficient systematically prioritizes under-represented training samples, improving generalizability on long-tailed or rare conditions. Overall, our work offers practical insights into the data and computation demands for efficient pretraining and downstream adaptation of medical vision-language foundation models.

Unpaired Image-to-Image Translation via a Self-Supervised Semantic Bridge

Adversarial diffusion and diffusion-inversion methods have advanced unpaired image-to-image translation, but each faces key limitations. Adversarial approaches require target-domain adversarial loss during training, which can limit generalization to unseen data, while diffusion-inversion methods often produce low-fidelity translations due to imperfect inversion into noise-latent representations. In this work, we propose the Self-Supervised Semantic Bridge (SSB), a versatile framework that integrates external semantic priors into diffusion bridge models to enable spatially faithful translation without cross-domain supervision. Our key idea is to leverage self-supervised visual encoders to learn representations that are invariant to appearance changes but capture geometric structure, forming a shared latent space that conditions the diffusion bridges. Extensive experiments show that SSB outperforms strong prior methods for challenging medical image synthesis in both in-domain and out-of-domain settings, and extends easily to high-quality text-guided editing.

Comp2Comp: Open-Source Software with FDA-Cleared Artificial Intelligence Algorithms for Computed Tomography Image Analysis

Artificial intelligence allows automatic extraction of imaging biomarkers from already-acquired radiologic images. This paradigm of opportunistic imaging adds value to medical imaging without additional imaging costs or patient radiation exposure. However, many open-source image analysis solutions lack rigorous validation while commercial solutions lack transparency, leading to unexpected failures when deployed. Here, we report development and validation for two of the first fully open-sourced, FDA-510(k)-cleared deep learning pipelines to mitigate both challenges: Abdominal Aortic Quantification (AAQ) and Bone Mineral Density (BMD) estimation are both offered within the Comp2Comp package for opportunistic analysis of computed tomography scans. AAQ segments the abdominal aorta to assess aneurysm size; BMD segments vertebral bodies to estimate trabecular bone density and osteoporosis risk. AAQ-derived maximal aortic diameters were compared against radiologist ground-truth measurements on 258 patient scans enriched for abdominal aortic aneurysms from four external institutions. BMD binary classifications (low vs. normal bone density) were compared against concurrent DXA scan ground truths obtained on 371 patient scans from four external institutions. AAQ had an overall mean absolute error of 1.57 mm (95% CI 1.38-1.80 mm). BMD had a sensitivity of 81.0% (95% CI 74.0-86.8%) and specificity of 78.4% (95% CI 72.3-83.7%). Comp2Comp AAQ and BMD demonstrated sufficient accuracy for clinical use. Open-sourcing these algorithms improves transparency of typically opaque FDA clearance processes, allows hospitals to test the algorithms before cumbersome clinical pilots, and provides researchers with best-in-class methods.

Automated Real-time Assessment of Intracranial Hemorrhage Detection AI Using an Ensembled Monitoring Model (EMM)

Artificial intelligence (AI) tools for radiology are commonly unmonitored once deployed. The lack of real-time case-by-case assessments of AI prediction confidence requires users to independently distinguish between trustworthy and unreliable AI predictions, which increases cognitive burden, reduces productivity, and potentially leads to misdiagnoses. To address these challenges, we introduce Ensembled Monitoring Model (EMM), a framework inspired by clinical consensus practices using multiple expert reviews. Designed specifically for black-box commercial AI products, EMM operates independently without requiring access to internal AI components or intermediate outputs, while still providing robust confidence measurements. Using intracranial hemorrhage detection as our test case on a large, diverse dataset of 2919 studies, we demonstrate that EMM successfully categorizes confidence in the AI-generated prediction, suggesting different actions and helping improve the overall performance of AI tools to ultimately reduce cognitive burden. Importantly, we provide key technical considerations and best practices for successfully translating EMM into clinical settings.

Efficient Noise Calculation in Deep Learning-based MRI Reconstructions

Accelerated MRI reconstruction involves solving an ill-posed inverse problem where noise in acquired data propagates to the reconstructed images. Noise analyses are central to MRI reconstruction for providing an explicit measure of solution fidelity and for guiding the design and deployment of novel reconstruction methods. However, deep learning (DL)-based reconstruction methods have often overlooked noise propagation due to inherent analytical and computational challenges, despite its critical importance. This work proposes a theoretically grounded, memory-efficient technique to calculate voxel-wise variance for quantifying uncertainty due to acquisition noise in accelerated MRI reconstructions. Our approach approximates noise covariance using the DL network's Jacobian, which is intractable to calculate. To circumvent this, we derive an unbiased estimator for the diagonal of this covariance matrix (voxel-wise variance) and introduce a Jacobian sketching technique to efficiently implement it. We evaluate our method on knee and brain MRI datasets for both data- and physics-driven networks trained in supervised and unsupervised manners. Compared to empirical references obtained via Monte Carlo simulations, our technique achieves near-equivalent performance while reducing computational and memory demands by an order of magnitude or more. Furthermore, our method is robust across varying input noise levels, acceleration factors, and diverse undersampling schemes, highlighting its broad applicability. Our work reintroduces accurate and efficient noise analysis as a central tenet of reconstruction algorithms, holding promise to reshape how we evaluate and deploy DL-based MRI. Our code will be made publicly available upon acceptance.

Time-to-Event Pretraining for 3D Medical Imaging

With the rise of medical foundation models and the growing availability of imaging data, scalable pretraining techniques offer a promising way to identify imaging biomarkers predictive of future disease risk. While current self-supervised methods for 3D medical imaging models capture local structural features like organ morphology, they fail to link pixel biomarkers with long-term health outcomes due to a missing context problem. Current approaches lack the temporal context necessary to identify biomarkers correlated with disease progression, as they rely on supervision derived only from images and concurrent text descriptions. To address this, we introduce time-to-event pretraining, a pretraining framework for 3D medical imaging models that leverages large-scale temporal supervision from paired, longitudinal electronic health records (EHRs). Using a dataset of 18,945 CT scans (4.2 million 2D images) and time-to-event distributions across thousands of EHR-derived tasks, our method improves outcome prediction, achieving an average AUROC increase of 23.7% and a 29.4% gain in Harrell's C-index across 8 benchmark tasks. Importantly, these gains are achieved without sacrificing diagnostic classification performance. This study lays the foundation for integrating longitudinal EHR and 3D imaging data to advance clinical risk prediction.