Abstract:Vision-language pretraining learns rich medical image representations from radiology reports, but previous model variants commonly operate within a single shared embedding space, so concept-level structure and interpretability must be recovered post hoc, limiting model transparency and, hence, clinical utility. We introduce RadPRISM, which makes a clinician-defined radiology schema a designated stratification axis: an on-premise large language model extracts per-concept text spans from free-text reports, and each clinical concept is aligned in its own dedicated visual subspace, turning concept stratification into direct, top-level alignment supervision. Instantiated on chest radiographs with a 19-concept schema over $203{,}602$ examinations from an internal multi-year archive, RadPRISM improved internal dataset zero-shot classification from $0.717$ (95% CI, $0.710-0.723$) to $0.868$ (95% CI, $0.863-0.872$) macro AUROC over a matched global-alignment baseline, performed on par with the purpose-built CARZero reference in external zero-shot classification while substantially outperforming it (up to 4.3-fold) in pointing-game visual grounding. In addition, a radiologist reader study demonstrated concept-stratified retrieval ability ($0.78$ macro retrieval correctness rate within rank 3), surfacing disentangled descriptive findings that report-level retrieval and fixed-label vocabularies cannot express. RadPRISM yields discriminative, spatially faithful, natively concept-stratified representations shaped by and transparently inspectable by clinicians.
Abstract:Large language models achieve high scores on medical knowledge assessments, yet clinical reasoning requires actively deciding what to investigate under uncertainty. We developed an agentic evaluation framework in hematologic oncology in which models must proactively request clinical data across three sequential rounds before committing to a diagnosis and treatment plan. Across 32 frontier models, the best achieved only 68% overall accuracy. Information utilization, the fraction of available data actually requested, was the strongest predictor of diagnostic accuracy (R = 0.69, P < 0.001), yet utilization collapsed from 57% to 26% in the final round, leaving molecular and cytogenetic data critical for treatment selection unexamined. Reasoning traces scored high on a clinical reasoning rubric (91% above threshold) but decorrelated from accuracy, revealing a gap between locally coherent rationales and globally correct conclusions. Error analysis identified search satisficing, anchoring and premature closure as the dominant failure modes, the same cognitive biases that characterize novice clinicians under dual-process models of diagnostic reasoning. These findings demonstrate that the primary limitation of current models in clinical oncology is not insufficient medical knowledge but a systematic failure of information-seeking under uncertainty.
Abstract:Question: Does atomic fact-checking, which decomposes AI treatment recommendations into individually verifiable claims linked to source guideline documents, increase clinician trust compared to traditional explainability approaches? Findings: In this randomized trial of 356 clinicians generating 7,476 trust ratings, atomic fact-checking produced a large effect on trust (Cohen's d = 0.94), increasing the proportion of clinicians expressing trust from 26.9% to 66.5%. Traditional transparency mechanisms showed a dose-response gradient of improvement over baseline (d = 0.25 to 0.50). Meaning: Decomposing AI recommendations into individually verifiable claims linked to source guidelines produces substantially higher clinician trust than traditional explainability approaches in high-stakes clinical decisions.
Abstract:Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.
Abstract:Multimodal large language models have demonstrated comparable performance to that of radiology trainees on multiple-choice board-style exams. However, to develop clinically useful multimodal LLM tools, high-quality benchmarks curated by domain experts are essential. To curate released and holdout datasets of 100 chest radiographic studies each and propose an artificial intelligence (AI)-assisted expert labeling procedure to allow radiologists to label studies more efficiently. A total of 13,735 deidentified chest radiographs and their corresponding reports from the MIDRC were used. GPT-4o extracted abnormal findings from the reports, which were then mapped to 12 benchmark labels with a locally hosted LLM (Phi-4-Reasoning). From these studies, 1,000 were sampled on the basis of the AI-suggested benchmark labels for expert review; the sampling algorithm ensured that the selected studies were clinically relevant and captured a range of difficulty levels. Seventeen chest radiologists participated, and they marked "Agree all", "Agree mostly" or "Disagree" to indicate their assessment of the correctness of the LLM suggested labels. Each chest radiograph was evaluated by three experts. Of these, at least two radiologists selected "Agree All" for 381 radiographs. From this set, 200 were selected, prioritizing those with less common or multiple finding labels, and divided into 100 released radiographs and 100 reserved as the holdout dataset. The holdout dataset is used exclusively by RSNA to independently evaluate different models. A benchmark of 200 chest radiographic studies with 12 benchmark labels was created and made publicly available https://imaging.rsna.org, with each chest radiograph verified by three radiologists. In addition, an AI-assisted labeling procedure was developed to help radiologists label at scale, minimize unnecessary omissions, and support a semicollaborative environment.




Abstract:Large language models (LLMs) exhibit extensive medical knowledge but are prone to hallucinations and inaccurate citations, which pose a challenge to their clinical adoption and regulatory compliance. Current methods, such as Retrieval Augmented Generation, partially address these issues by grounding answers in source documents, but hallucinations and low fact-level explainability persist. In this work, we introduce a novel atomic fact-checking framework designed to enhance the reliability and explainability of LLMs used in medical long-form question answering. This method decomposes LLM-generated responses into discrete, verifiable units called atomic facts, each of which is independently verified against an authoritative knowledge base of medical guidelines. This approach enables targeted correction of errors and direct tracing to source literature, thereby improving the factual accuracy and explainability of medical Q&A. Extensive evaluation using multi-reader assessments by medical experts and an automated open Q&A benchmark demonstrated significant improvements in factual accuracy and explainability. Our framework achieved up to a 40% overall answer improvement and a 50% hallucination detection rate. The ability to trace each atomic fact back to the most relevant chunks from the database provides a granular, transparent explanation of the generated responses, addressing a major gap in current medical AI applications. This work represents a crucial step towards more trustworthy and reliable clinical applications of LLMs, addressing key prerequisites for clinical application and fostering greater confidence in AI-assisted healthcare.
Abstract:Kidney abnormality segmentation has important potential to enhance the clinical workflow, especially in settings requiring quantitative assessments. Kidney volume could serve as an important biomarker for renal diseases, with changes in volume correlating directly with kidney function. Currently, clinical practice often relies on subjective visual assessment for evaluating kidney size and abnormalities, including tumors and cysts, which are typically staged based on diameter, volume, and anatomical location. To support a more objective and reproducible approach, this research aims to develop a robust, thoroughly validated kidney abnormality segmentation algorithm, made publicly available for clinical and research use. We employ publicly available training datasets and leverage the state-of-the-art medical image segmentation framework nnU-Net. Validation is conducted using both proprietary and public test datasets, with segmentation performance quantified by Dice coefficient and the 95th percentile Hausdorff distance. Furthermore, we analyze robustness across subgroups based on patient sex, age, CT contrast phases, and tumor histologic subtypes. Our findings demonstrate that our segmentation algorithm, trained exclusively on publicly available data, generalizes effectively to external test sets and outperforms existing state-of-the-art models across all tested datasets. Subgroup analyses reveal consistent high performance, indicating strong robustness and reliability. The developed algorithm and associated code are publicly accessible at https://github.com/DIAGNijmegen/oncology-kidney-abnormality-segmentation.




Abstract:Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.




Abstract:Purpose: To examine whether incorporating anatomical awareness into a deep learning model can improve generalizability and enable prediction of disease progression. Methods: This retrospective multicenter study included conventional pelvic radiographs of 4 different patient cohorts focusing on axial spondyloarthritis (axSpA) collected at university and community hospitals. The first cohort, which consisted of 1483 radiographs, was split into training (n=1261) and validation (n=222) sets. The other cohorts comprising 436, 340, and 163 patients, respectively, were used as independent test datasets. For the second cohort, follow-up data of 311 patients was used to examine progression prediction capabilities. Two neural networks were trained, one on images cropped to the bounding box of the sacroiliac joints (anatomy-aware) and the other one on full radiographs. The performance of the models was compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: On the three test datasets, the standard model achieved AUC scores of 0.853, 0.817, 0.947, with an accuracy of 0.770, 0.724, 0.850. Whereas the anatomy-aware model achieved AUC scores of 0.899, 0.846, 0.957, with an accuracy of 0.821, 0.744, 0.906, respectively. The patients who were identified as high risk by the anatomy aware model had an odds ratio of 2.16 (95% CI: 1.19, 3.86) for having progression of radiographic sacroiliitis within 2 years. Conclusion: Anatomical awareness can improve the generalizability of a deep learning model in detecting radiographic sacroiliitis. The model is published as fully open source alongside this study.




Abstract:Purpose: To introduce a deep learning model capable of multi-organ segmentation in MRI scans, offering a solution to the current limitations in MRI analysis due to challenges in resolution, standardized intensity values, and variability in sequences. Materials and Methods: he model was trained on 1,200 manually annotated MRI scans from the UK Biobank, 221 in-house MRI scans and 1228 CT scans, leveraging cross-modality transfer learning from CT segmentation models. A human-in-the-loop annotation workflow was employed to efficiently create high-quality segmentations. The model's performance was evaluated on NAKO and the AMOS22 dataset containing 600 and 60 MRI examinations. Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) was used to assess segmentation accuracy. The model will be open sourced. Results: The model showcased high accuracy in segmenting well-defined organs, achieving Dice Similarity Coefficient (DSC) scores of 0.97 for the right and left lungs, and 0.95 for the heart. It also demonstrated robustness in organs like the liver (DSC: 0.96) and kidneys (DSC: 0.95 left, 0.95 right), which present more variability. However, segmentation of smaller and complex structures such as the portal and splenic veins (DSC: 0.54) and adrenal glands (DSC: 0.65 left, 0.61 right) revealed the need for further model optimization. Conclusion: The proposed model is a robust, tool for accurate segmentation of 40 anatomical structures in MRI and CT images. By leveraging cross-modality learning and interactive annotation, the model achieves strong performance and generalizability across diverse datasets, making it a valuable resource for researchers and clinicians. It is open source and can be downloaded from https://github.com/hhaentze/MRSegmentator.