on behalf of the PINNACLE consortium
Abstract:Deep learning-based medical image segmentation is increasingly used to support clinical diagnosis and develop new treatment strategies. However, model performance remains limited by the scarcity of high-quality annotated data and insufficient generalization across imaging protocols. This limitation is particularly evident in MRI and CT, where models are typically trained on a single acquisition sequence and exhibit reduced robustness when applied to unseen sequences or contrasts. Although data augmentation is widely used to improve general robustness on medical images, its impact on cross-modality generalization has not been quantitatively explored. In this work, we study a targeted set of data augmentation techniques designed to improve cross-modality transfer. We train three spine segmentation models, each on a single-modality/sequence dataset, and evaluate them across seven out-of-distribution datasets (spanning CT and MRI), reflecting a realistic single-sequence training and multi-sequence/contrast/modality deployment scenario. Our results demonstrate substantial performance gains on unseen domains (average Dice gain of 155 %) while preserving in-domain accuracy (average Dice decrease of 0.008 %), including effective transfer between CT and MRI. To mitigate the computational cost typically associated with strong data augmentation, we implement GPU-optimized augmentations that maintain, and even improve, training efficiency by approximately 10 %. We release our approach as an open-source toolbox, enabling seamless integration into commonly used frameworks such as nnUNet and MONAI. These augmentations significantly enhance robustness to heterogeneous clinical imaging scenarios without compromising training speed.
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:Training vision-language models (VLMs) for medical report generation is often hindered by the scarcity of high-quality annotated data. This work evaluates the use of a weighted loss function to improve data efficiency. Compared to standard cross-entropy loss, which treats all token prediction errors equally, the reweighted loss shifts the focus to semantically salient tokens with outsized clinical importance. In experiments on ophthalmological report generation, we show that this simple method improves efficiency across multiple data scales, achieving similar report quality with up to ten times less training data.
Abstract:We measure how much one extra recurrence is worth to a looped (depth-recurrent) language model, in equivalent unique parameters. From an iso-depth sweep of 116 pretraining runs across recurrence counts $r \in \{1, 2, 4, 8\}$ spanning ${\sim}50\times$ in training compute, we fit a joint scaling law $L = E + A\,(N_\text{once} + r^{\varphi} N_\text{rec})^{-α} + B\,D^{-β}$ and recover a new recurrence-equivalence exponent $\varphi = 0.46$ at $R^2 = 0.997$. Intuitively, $\varphi$ tells us whether looping a block $r$ times is equivalent in validation loss to $r$ unique blocks of a non-looped model (full equivalence, $\varphi{=}1$) or to a single block run repeatedly with no capacity gain ($\varphi{=}0$). Our $\varphi = 0.46$ sits in between, so each additional recurrence predictably increases validation loss at matched training compute. For example, at $r{=}4$ a 410M looped model performs on par with a 580M non-looped model, but pays the training cost of a 1B non-looped one. On a five-axis downstream evaluation, the gap persists on parametric-knowledge tasks and closes on simple open-book tasks, while reasoning tasks are not resolvable at our compute budgets. For any looped LM, our $\varphi$ converts the design choice of $r$ into a predictable validation-loss cost, and future training recipes and architectures can be compared by how much they raise $\varphi$ above $0.46$.
Abstract:Tool-augmented large language model (LLM) agents can orchestrate specialist classifiers, segmentation models, and visual question-answering modules to interpret chest X-rays. However, these agents still solve each case in isolation: they fail to accumulate experience across cases, correct recurrent reasoning mistakes, or adapt their tool-use behavior without expensive reinforcement learning. While a radiologist naturally improves with every case, current agents remain static. In this work, we propose Evo-MedAgent, a self-evolving memory module that equips a medical agent with the capacity for inter-case learning at test time. Our memory comprises three complementary stores: (1)~\emph{Retrospective Clinical Episodes} that retrieve problem-solving experiences from similar past cases, (2)~an \emph{Adaptive Procedural Heuristics} bank curating priority-tagged diagnostic rules that evolves via reflection, much like a physician refining their internal criteria, and (3)~a \emph{Tool Reliability Controller} that tracks per-tool trustworthiness. On ChestAgentBench, Evo-MedAgent raises multiple-choice question (MCQ) accuracy from 0.68 to 0.79 on GPT-5-mini, and from 0.76 to 0.87 on Gemini-3 Flash. With a strong base model, evolving memory improves performance more effectively than orchestrating external tools on qualitative diagnostic tasks. Because Evo-MedAgent requires no training, its per-case overhead is bounded by one additional retrieval pass and a single reflection call, making it deployable on top of any frozen model.
Abstract:AI-based image reconstruction models are increasingly deployed in clinical workflows to improve image quality from noisy data, such as low-dose X-rays or accelerated MRI scans. However, these models are typically evaluated using pixel-level metrics like PSNR, leaving their impact on downstream diagnostic performance and fairness unclear. We introduce a scalable evaluation framework that applies reconstruction and diagnostic AI models in tandem, which we apply to two tasks (classification, segmentation), three reconstruction approaches (U-Net, GAN, diffusion), and two data types (X-ray, MRI) to assess the potential downstream implications of reconstruction. We find that conventional reconstruction metrics poorly track task performance, where diagnostic accuracy remains largely stable even as reconstruction PSNR declines with increasing image noise. Fairness metrics exhibit greater variability, with reconstruction sometimes amplifying demographic biases, particularly regarding patient sex. However, the overall magnitude of this additional bias is modest compared to the inherent biases already present in diagnostic models. To explore potential bias mitigation, we adapt two strategies from classification literature to the reconstruction setting, but observe limited efficacy. Overall, our findings emphasize the importance of holistic performance and fairness assessments throughout the entire medical imaging workflow, especially as generative reconstruction models are increasingly deployed.
Abstract:Survival analysis is crucial for many medical applications but remains challenging for modern machine learning due to limited data, censoring, and the heterogeneity of tabular covariates. While the prior-fitted paradigm, which relies on pretraining models on large collections of synthetic datasets, has recently facilitated tabular foundation models for classification and regression, its suitability for time-to-event modeling remains unclear. We propose a flexible survival data generation framework that defines a rich survival prior with explicit control over covariates and time-event distributions. Building on this prior, we introduce Survival In-Context (SIC), a prior-fitted in-context learning model for survival analysis that is pretrained exclusively on synthetic data. SIC produces individualized survival prediction in a single forward pass, requiring no task-specific training or hyperparameter tuning. Across a broad evaluation on real-world survival datasets, SIC achieves competitive or superior performance compared to classical and deep survival models, particularly in medium-sized data regimes, highlighting the promise of prior-fitted foundation models for survival analysis. The code will be made available upon publication.
Abstract:Currently, evaluating vision-language models (VLMs) in medical imaging tasks oversimplifies clinical reality by relying on pre-selected 2D images that demand significant manual labor to curate. This setup misses the core challenge of realworld diagnostics: a true clinical agent must actively navigate full 3D volumes across multiple sequences or modalities to gather evidence and ultimately support a final decision. To address this, we propose MEDOPENCLAW, an auditable runtime designed to let VLMs operate dynamically within standard medical tools or viewers (e.g., 3D Slicer). On top of this runtime, we introduce MEDFLOWBENCH, a full-study medical imaging benchmark covering multi-sequence brain MRI and lung CT/PET. It systematically evaluates medical agentic capabilities across viewer-only, tool-use, and open-method tracks. Initial results reveal a critical insight: while state-of-the-art LLMs/VLMs (e.g., Gemini 3.1 Pro and GPT-5.4) can successfully navigate the viewer to solve basic study-level tasks, their performance paradoxically degrades when given access to professional support tools due to a lack of precise spatial grounding. By bridging the gap between static-image perception and interactive clinical workflows, MEDOPENCLAW and MEDFLOWBENCH establish a reproducible foundation for developing auditable, full-study medical imaging agents.
Abstract:Segmentation of enhancement in LGE cardiac MRI is critical for diagnosing various ischemic and non-ischemic cardiomyopathies. However, creating pixel-level annotations for these images is challenging and labor-intensive, leading to limited availability of annotated data. Generative models, particularly diffusion models, offer promise for synthetic data generation, yet many rely on large training datasets and often struggle with fine-grained conditioning control, especially for small or localized features. We introduce LGESynthNet, a latent diffusion-based framework for controllable enhancement synthesis, enabling explicit control over size, location, and transmural extent. Formulated as inpainting using a ControlNet-based architecture, the model integrates: (a) a reward model for conditioning-specific supervision, (b) a captioning module for anatomically descriptive text prompts, and (c) a biomedical text encoder. Trained on just 429 images (79 patients), it produces realistic, anatomically coherent samples. A quality control filter selects outputs with high conditioning-fidelity, which when used for training augmentation, improve downstream segmentation and detection performance, by up-to 6 and 20 points respectively.
Abstract:Cardiovascular diseases are the leading cause of death. Cardiac phenotypes (CPs), e.g., ejection fraction, are the gold standard for assessing cardiac health, but they are derived from cine cardiac magnetic resonance imaging (CMR), which is costly and requires high spatio-temporal resolution. Every magnetic resonance (MR) examination begins with rapid and coarse localizers for scan planning, which are discarded thereafter. Despite non-diagnostic image quality and lack of temporal information, localizers can provide valuable structural information rapidly. In addition to imaging, patient-level information, including demographics and lifestyle, influence the cardiac health assessment. Electrocardiograms (ECGs) are inexpensive, routinely ordered in clinical practice, and capture the temporal activity of the heart. Here, we introduce C-TRIP (Cardiac Tri-modal Representations for Imaging Phenotypes), a multi-modal framework that aligns localizer MRI, ECG signals, and tabular metadata to learn a robust latent space and predict CPs using localizer images as an opportunistic alternative to CMR. By combining these three modalities, we leverage cheap spatial and temporal information from localizers, and ECG, respectively while benefiting from patient-specific context provided by tabular data. Our pipeline consists of three stages. First, encoders are trained independently to learn uni-modal representations. The second stage fuses the pre-trained encoders to unify the latent space. The final stage uses the enriched representation space for CP prediction, with inference performed exclusively on localizer MRI. Proposed C-TRIP yields accurate functional CPs, and high correlations for structural CPs. Since localizers are inherently rapid and low-cost, our C-TRIP framework could enable better accessibility for CP estimation.