RareAgents: Autonomous Multi-disciplinary Team for Rare Disease Diagnosis and Treatment

Rare diseases, despite their low individual incidence, collectively impact around 300 million people worldwide due to the huge number of diseases. The complexity of symptoms and the shortage of specialized doctors with relevant experience make diagnosing and treating rare diseases more challenging than common diseases. Recently, agents powered by large language models (LLMs) have demonstrated notable improvements across various domains. In the medical field, some agent methods have outperformed direct prompts in question-answering tasks from medical exams. However, current agent frameworks lack adaptation for real-world clinical scenarios, especially those involving the intricate demands of rare diseases. To address these challenges, we present RareAgents, the first multi-disciplinary team of LLM-based agents tailored to the complex clinical context of rare diseases. RareAgents integrates advanced planning capabilities, memory mechanisms, and medical tools utilization, leveraging Llama-3.1-8B/70B as the base model. Experimental results show that RareAgents surpasses state-of-the-art domain-specific models, GPT-4o, and existing agent frameworks in both differential diagnosis and medication recommendation for rare diseases. Furthermore, we contribute a novel dataset, MIMIC-IV-Ext-Rare, derived from MIMIC-IV, to support further advancements in this field.

VividMed: Vision Language Model with Versatile Visual Grounding for Medicine

Recent advancements in Vision Language Models (VLMs) have demonstrated remarkable promise in generating visually grounded responses. However, their application in the medical domain is hindered by unique challenges. For instance, most VLMs rely on a single method of visual grounding, whereas complex medical tasks demand more versatile approaches. Additionally, while most VLMs process only 2D images, a large portion of medical images are 3D. The lack of medical data further compounds these obstacles. To address these challenges, we present VividMed, a vision language model with versatile visual grounding for medicine. Our model supports generating both semantic segmentation masks and instance-level bounding boxes, and accommodates various imaging modalities, including both 2D and 3D data. We design a three-stage training procedure and an automatic data synthesis pipeline based on open datasets and models. Besides visual grounding tasks, VividMed also excels in other common downstream tasks, including Visual Question Answering (VQA) and report generation. Ablation studies empirically show that the integration of visual grounding ability leads to improved performance on these tasks. Our code is publicly available at https://github.com/function2-llx/MMMM.

RareBench: Can LLMs Serve as Rare Diseases Specialists?

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

Pre-trained Universal Medical Image Transformer

Self-supervised learning has emerged as a viable method to leverage the abundance of unlabeled medical imaging data, addressing the challenge of labeled data scarcity in medical image analysis. In particular, masked image modeling (MIM) with visual token reconstruction has shown promising results in the general computer vision (CV) domain and serves as a candidate for medical image analysis. However, the presence of heterogeneous 2D and 3D medical images often limits the volume and diversity of training data that can be effectively used for a single model structure. In this work, we propose a spatially adaptive convolution (SAC) module, which adaptively adjusts convolution parameters based on the voxel spacing of the input images. Employing this SAC module, we build a universal visual tokenizer and a universal Vision Transformer (ViT) capable of effectively processing a wide range of medical images with various imaging modalities and spatial properties. Moreover, in order to enhance the robustness of the visual tokenizer's reconstruction objective for MIM, we suggest to generalize the discrete token output of the visual tokenizer to a probabilistic soft token. We show that the generalized soft token representation can be effectively integrated with the prior distribution regularization through a constructive interpretation. As a result, we pre-train a universal visual tokenizer followed by a universal ViT via visual token reconstruction on 55 public medical image datasets, comprising over 9 million 2D slices (including over 48,000 3D images). This represents the largest, most comprehensive, and diverse dataset for pre-training 3D medical image models to our knowledge. Experimental results on downstream medical image classification and segmentation tasks demonstrate the superior performance of our model and improved label efficiency.