Kevin Brown

Zekai Chen, Devansh Agarwal, Kshitij Aggarwal et al.

Recently, masked image modeling (MIM) has gained considerable attention due to its capacity to learn from vast amounts of unlabeled data and has been demonstrated to be effective on a wide variety of vision tasks involving natural images. Meanwhile, the potential of self-supervised learning in modeling 3D medical images is anticipated to be immense due to the high quantities of unlabeled images, and the expense and difficulty of quality labels. However, MIM's applicability to medical images remains uncertain. In this paper, we demonstrate that masked image modeling approaches can also advance 3D medical images analysis in addition to natural images. We study how masked image modeling strategies leverage performance from the viewpoints of 3D medical image segmentation as a representative downstream task: i) when compared to naive contrastive learning, masked image modeling approaches accelerate the convergence of supervised training even faster (1.40$\times$) and ultimately produce a higher dice score; ii) predicting raw voxel values with a high masking ratio and a relatively smaller patch size is non-trivial self-supervised pretext-task for medical images modeling; iii) a lightweight decoder or projection head design for reconstruction is powerful for masked image modeling on 3D medical images which speeds up training and reduce cost; iv) finally, we also investigate the effectiveness of MIM methods under different practical scenarios where different image resolutions and labeled data ratios are applied.

Zekai Chen, Mariann Micsinai Balan, Kevin Brown

Clinical prediction is an essential task in the healthcare industry. However, the recent success of transformers, on which large language models are built, has not been extended to this domain. In this research, we explore the use of transformers and language models in prognostic prediction for immunotherapy using real-world patients' clinical data and molecular profiles. This paper investigates the potential of transformers to improve clinical prediction compared to conventional machine learning approaches and addresses the challenge of few-shot learning in predicting rare disease areas. The study benchmarks the efficacy of baselines and language models on prognostic prediction across multiple cancer types and investigates the impact of different pretrained language models under few-shot regimes. The results demonstrate significant improvements in accuracy and highlight the potential of NLP in clinical research to improve early detection and intervention for different diseases.

Irsyad Adam, Zekai Chen, David Laprade et al.

Large language models (LLMs) trained with next-word-prediction have achieved success as clinical foundation models. Representations from these language backbones yield strong linear probe performance across biomedical tasks, suggesting that patient semantics emerge from next-token prediction at scale. However, this paradigm treats patients as a document to be summarized rather than a dynamical system to be simulated; a patient's trajectory emerges from their state evolving under interventions and time, requiring models that simulate dynamics rather than predict tokens. To address this, we introduce SMB-Structure, a world model for structured EHR that grounds a joint-embedding prediction architecture (JEPA) with next-token prediction (SFT). SFT grounds our model to reconstruct future patient states in token space, while JEPA predicts those futures in latent space from the initial patient representation alone, forcing trajectory dynamics to be encoded before the next state is observed. We validate across two large-scale cohorts: Memorial Sloan Kettering (23,319 oncology patients; 323,000+ patient-years) and INSPECT (19,402 pulmonary embolism patients). Using a linear probe evaluated at multiple points along the disease trajectory, we demonstrate that our training paradigm learns embeddings that capture disease dynamics not recoverable by autoregressive baselines, enabling SMB-Structure to achieve competitive performance on complex tasks characterized by high patient heterogeneity. Model weights are available at https://huggingface.co/standardmodelbio/SMB-v1-1.7B-Structure.

Zekai Chen, Arda Pekis, Kevin Brown

Multi-modal learning has significantly advanced generative AI, especially in vision-language modeling. Innovations like GPT-4V and open-source projects such as LLaVA have enabled robust conversational agents capable of zero-shot task completions. However, applying these technologies in the biomedical field presents unique challenges. Recent initiatives like LLaVA-Med have started to adapt instruction-tuning for biomedical contexts using large datasets such as PMC-15M. Our research offers three key contributions: (i) we present a new instruct dataset enriched with medical image-text pairs from Claude3-Opus and LLaMA3 70B, (ii) we propose a novel image encoding strategy using hierarchical representations to improve fine-grained biomedical visual comprehension, and (iii) we develop the Llama3-Med model, which achieves state-of-the-art zero-shot performance on biomedical visual question answering benchmarks, with an average performance improvement of over 10% compared to previous methods. These advancements provide more accurate and reliable tools for medical professionals, bridging gaps in current multi-modal conversational assistants and promoting further innovations in medical AI.

Anjany Sekuboyina, Malek E. Husseini, Amirhossein Bayat et al.

Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision-support systems for diagnosis, surgery planning, and population-based analysis on spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms towards labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel-level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the the results of this evaluation and further investigate the performance-variation at vertebra-level, scan-level, and at different fields-of-view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The content and code concerning VerSe can be accessed at: https://github.com/anjany/verse.

Zekai Chen, Arda Pekis, Kevin Brown

Electronic Health Records (EHRs) contain rich temporal dynamics that conventional encoding approaches fail to adequately capture. While Large Language Models (LLMs) show promise for EHR modeling, they struggle to reason about sequential clinical events and temporal dependencies. We propose Next Event Prediction (NEP), a framework that enhances LLMs' temporal reasoning through autoregressive fine-tuning on clinical event sequences. By reformulating EHRs as timestamped event chains and predicting future medical events, NEP explicitly models disease progression patterns and causal relationships. Extensive evaluations across oncology survival prediction and clinical diagnosis tasks demonstrate NEP's superiority, outperforming specialized EHR models by 4.6% AUROC and general-purpose LLMs by 7.2% C-index in temporal reasoning tasks. Our analyses reveal dual benefits: state-of-the-art prediction accuracy combined with clinically interpretable attention patterns that align with known disease pathways.

Irsyad Adam, Zekai Chen, David Laub et al.

Proteomics data is essential to pathogenic understanding of a disease phenotype. In cancer, analysis of molecular signatures enables precision medicine through the identification of biological processes that drive individualized tumor progression, therapeutic resistance, and clinical heterogeneity. Recent advances in multimodal large language models (LLMs) have shown remarkable capacity to integrate and reason across heterogeneous data modalities. However, performing multi-modal language modeling for molecular understanding of patient-specific proteomics remains a significant challenge due to two barriers: (1) the lack of instruction-tuning datasets that enable clinical interpretation from proteomics data, and (2) the absence of language modeling architectures designed to capture the rich heterogeneity of molecular data. In this work, we introduce CPTAC-PROTSTRUCT, the first instruction tuning dataset for molecular understanding of oncology, comprising over 400k open-ended examples derived from individualized proteomic profiles curated from the largest national proteomics cancer study (CPTAC). Additionally, we propose KRONOS (Knowledge Representation of patient Omics Networks in Oncology via Structured tuning), a novel graph-LLM framework that leverages molecular interaction topology with proteomics to learn patient-specific graph representations for enhanced clinical reasoning. We show that KRONOS achieves competitive performance across benchmark clinical tasks, including molecular classification, temporal trajectory modeling, and tumor stage prediction from proteomics data. Ultimately, this approach empowers LLMs to understand patient-level pathogenesis, advancing precision medicine through more accurate diagnosis, prognosis, and treatment stratification.