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Clinical decision-making is one of the most impactful parts of a physician’s responsibilities and stands to benefit greatly from artificial intelligence solutions and large language models (LLMs) in particular. However, while LLMs have achieved excellent performance on medical licensing exams, these tests fail to assess many skills necessary for deployment in a realistic clinical decision-making environment, including gathering information, adhering to guidelines, and integrating into clinical workflows. Here we have created a curated dataset based on the Medical Information Mart for Intensive Care database spanning 2,400 real patient cases and four common abdominal pathologies as well as a framework to simulate a realistic clinical setting. We show that current state-of-the-art LLMs do not accurately diagnose patients across all pathologies (performing significantly worse than physicians), follow neither diagnostic nor treatment guidelines, and cannot interpret laboratory results, thus posing a serious risk to the health of patients. Furthermore, we move beyond diagnostic accuracy and demonstrate that they cannot be easily integrated into existing workflows because they often fail to follow instructions and are sensitive to both the quantity and order of information. Overall, our analysis reveals that LLMs are currently not ready for autonomous clinical decision-making while providing a dataset and framework to guide future studies. Using a curated dataset of 2,400 cases and a framework to simulate a realistic clinical setting, current large language models are shown to incur substantial pitfalls when used for autonomous clinical decision-making.

Clinicians spend significant time reviewing medical images and transcribing findings. By integrating visual and textual data, foundation models have the potential to reduce workloads and boost efficiency, yet their practical clinical value remains uncertain. In this study, we find that OpenAI’s ChatGPT-4o and two medical vision-language models (VLMs) significantly underperform ophthalmologists in key tasks for age-related macular degeneration (AMD). To address this, we developed a dedicated training curriculum, designed by domain specialists, to optimize VLMs for tasks related to clinical decision making. The resulting model, RetinaVLM-Specialist, significantly outperforms foundation medical VLMs and ChatGPT-4o in AMD disease staging (F1: 0.63 vs. 0.33) and referral (0.67 vs. 0.50), achieving performance comparable to junior ophthalmologists. In a reader study, two senior ophthalmologists confirmed that RetinaVLM’s reports were substantially more accurate than those written by ChatGPT-4o (64.3% vs. 14.3%). Overall, our curriculum-based approach offers a blueprint for adapting foundation models to real-world medical applications.

Vision foundation models (FMs) achieve state-of-the-art performance in medical imaging. However, they encode information in abstract latent representations that clinicians cannot interrogate or verify. The goal of this study is to investigate Sparse Autoencoders (SAEs) for replacing opaque FM image representations with human-interpretable, sparse features. We train SAEs on embeddings from BiomedParse (biomedical) and DINOv3 (general-purpose) using 909,873 CT and MRI 2D image slices from the TotalSegmentator dataset. We find that learned sparse features: (a) reconstruct original embeddings with high fidelity (R2 up to 0.941) and recover up to 87.8% of downstream performance using only 10 features (99.4% dimensionality reduction), (b) preserve semantic fidelity in image retrieval tasks, (c) correspond to specific concepts that can be expressed in language using large language model (LLM)-based auto-interpretation. (d) bridge clinical language and abstract latent representations in zero-shot language-driven image retrieval. Our work indicates SAEs are a promising pathway towards interpretable, concept-driven medical vision systems. Code repository: https://github.com/pwesp/sail.

Reusing the early layers of cohort-trained INRs as initialization for new signals has been shown to accelerate and improve signal fitting, yet it remains unclear which layers of the shared encoder learn transferable representations and what those representations encode. We address both questions for two standard backbones, SIREN and Fourier-feature MLPs (FFMLP). First, sweeping the freeze depth across the shared encoder at test time, we find that the optimum coincides with the layer of highest weight stable rank. Moreover, freezing at this depth matches or improves on the standard fine-tuning recipe across all our experiments. Second, identifying which layer transfers does not characterize what that layer encodes. To address this we adopt sparse autoencoders (SAEs), the dominant tool in mechanistic interpretability, and present the first SAE decomposition of INR activations into sparse dictionary atoms. Interestingly, SIREN and FFMLP achieve comparable cohort-fitting quality, but learn qualitatively different dictionaries. Cohort SIREN's atoms are localized, tiling the coordinate plane such that each atom fires in a confined region independent of cohort content. Cohort FFMLP's atoms are image-spanning, tracing the contours of memorized cohort signals. Single-atom ablations confirm causal use of these dictionaries: a single FFMLP atom out of 4096 can drop PSNR by up to 10.6 dB across the image, while SIREN ablations remain confined to where the atom fires. Together, these results give the first mechanistic account of what transfers in cohort-trained INRs and turn their activations into inspectable dictionary atoms. These tools open a path towards characterizing what INRs encode and towards architectures designed for generalization rather than memorization.

Magnetic resonance imaging (MRI) is an invaluable tool for clinical and research applications. Yet, variations in scanners and acquisition parameters cause inconsistencies in image contrast, hindering data comparability and reproducibility across datasets and clinical studies. Existing scanner harmonization methods, designed to address this challenge, face limitations, such as requiring traveling subjects or struggling to generalize to unseen domains. We propose a novel approach using a conditioned diffusion autoencoder with a contrastive loss and domain-agnostic contrast augmentation to harmonize MR images across scanners while preserving subject-specific anatomy. Our method enables brain MRI synthesis from a single reference image. It outperforms baseline techniques, achieving a +7% PSNR improvement on a traveling subjects dataset and +18% improvement on age regression in unseen. Our model provides robust, effective harmonization of brain MRIs to target scanners without requiring fine-tuning. This advancement promises to enhance comparability, reproducibility, and generalizability in multi-site and longitudinal clinical studies, ultimately contributing to improved healthcare outcomes.

Recent medical multimodal foundation models are built as multimodal LLMs (MLLMs) by connecting a CLIP-pretrained vision encoder to an LLM using LLaVA-style finetuning. This two-stage, decoupled approach introduces a projection layer that can distort visual features. This is especially concerning in medical imaging where subtle cues are essential for accurate diagnoses. In contrast, early-fusion generative approaches such as Chameleon eliminate the projection bottleneck by processing image and text tokens within a single unified sequence, enabling joint representation learning that leverages the inductive priors of language models. We present CheXmix, a unified early-fusion generative model trained on a large corpus of chest X-rays paired with radiology reports. We expand on Chameleon's autoregressive framework by introducing a two-stage multimodal generative pretraining strategy that combines the representational strengths of masked autoencoders with MLLMs. The resulting models are highly flexible, supporting both discriminative and generative tasks at both coarse and fine-grained scales. Our approach outperforms well-established generative models across all masking ratios by 6.0% and surpasses CheXagent by 8.6% on AUROC at high image masking ratios on the CheXpert classification task. We further inpaint images over 51.0% better than text-only generative models and outperform CheXagent by 45% on the GREEN metric for radiology report generation. These results demonstrate that CheXmix captures fine-grained information across a broad spectrum of chest X-ray tasks. Our code is at: https://github.com/StanfordMIMI/CheXmix.

Vessels are complex structures in the body that have been studied extensively in multiple representations. While voxelization is the most common of them, meshes and parametric models are critical in various applications due to their desirable properties. However, these representations are typically extracted through segmentations and used disjointly from each other. We propose a framework that joins the three representations under differentiable transformations. By leveraging differentiable voxelization, we automatically extract a parametric shape model of the vessels through shape-to-segmentation fitting, where we learn shape parameters from segmentations without the explicit need for ground-truth shape parameters. The vessel is parametrized as centerlines and radii using cubic B-splines, ensuring smoothness and continuity by construction. Meshes are differentiably extracted from the learned shape parameters, resulting in high-fidelity meshes that can be manipulated post-fit. Our method can accurately capture the geometry of complex vessels, as demonstrated by the volumetric fits in experiments on aortas, aneurysms, and brain vessels.

Analyzing temporal developments is crucial for the accurate prognosis of many medical conditions. Temporal changes that occur over short time scales are key to assessing the health of physiological functions, such as the cardiac cycle. Moreover, tracking longer term developments that occur over months or years in evolving processes, such as age-related macular degeneration (AMD), is essential for accurate prognosis. Despite the importance of both short and long term analysis to clinical decision making, they remain understudied in medical deep learning. State of the art methods for spatiotemporal representation learning, developed for short natural videos, prioritize the detection of temporal constants rather than temporal developments. Moreover, they do not account for varying time intervals between acquisitions, which are essential for contextualizing observed changes. To address these issues, we propose two approaches. First, we combine clip-level contrastive learning with a novel temporal embedding to adapt to irregular time series. Second, we propose masking and predicting latent frame representations of the temporal sequence. Our two approaches outperform all prior methods on temporally-dependent tasks including cardiac output estimation and three prognostic AMD tasks. Overall, this enables the automated analysis of temporal patterns which are typically overlooked in applications of deep learning to medicine.

Clinicians spend a significant amount of time reviewing medical images and transcribing their findings regarding patient diagnosis, referral and treatment in text form. Vision-language models (VLMs), which automatically interpret images and summarize their findings as text, have enormous potential to alleviate clinical workloads and increase patient access to high-quality medical care. While foundational models have stirred considerable interest in the medical community, it is unclear whether their general capabilities translate to real-world clinical utility. In this work, we demonstrate that OpenAI's ChatGPT-4o model, in addition to two foundation VLMs designed for medical use, markedly underperform compared to practicing ophthalmologists on specialist tasks crucial to the care of patients with age-related macular degeneration (AMD). To address this, we initially identified the essential capabilities required for image-based clinical decision-making, and then developed a curriculum to selectively train VLMs in these skills. The resulting model, RetinaVLM, can be instructed to write reports that significantly outperform those written by leading foundation medical VLMs and ChatGPT-4o in disease staging (F1 score of 0.63 vs. 0.33) and patient referral (0.67 vs. 0.50), and approaches the diagnostic performance of junior ophthalmologists (who achieve 0.77 and 0.78 on the respective tasks). Furthermore, in a single-blind reader study two senior ophthalmologists with up to 32 years of experience found RetinaVLM's reports were found to be substantially more accurate than those by ChatGPT-4o (64.3% vs. 14.3%). These results reinforce that our curriculum-based approach provides a blueprint towards specializing foundation medical VLMs for real-world clinical tasks.

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images.