A Perspective for Adapting Generalist AI to Specialized Medical AI Applications and Their Challenges

The integration of Large Language Models (LLMs) into medical applications has sparked widespread interest across the healthcare industry, from drug discovery and development to clinical decision support, assisting telemedicine, medical devices, and healthcare insurance applications. This perspective paper aims to discuss the inner workings of building LLM-powered medical AI applications and introduces a comprehensive framework for their development. We review existing literature and outline the unique challenges of applying LLMs in specialized medical contexts. Additionally, we introduce a three-step framework to organize medical LLM research activities: 1) Modeling: breaking down complex medical workflows into manageable steps for developing medical-specific models; 2) Optimization: optimizing the model performance with crafted prompts and integrating external knowledge and tools, and 3) System engineering: decomposing complex tasks into subtasks and leveraging human expertise for building medical AI applications. Furthermore, we offer a detailed use case playbook that describes various LLM-powered medical AI applications, such as optimizing clinical trial design, enhancing clinical decision support, and advancing medical imaging analysis. Finally, we discuss various challenges and considerations for building medical AI applications with LLMs, such as handling hallucination issues, data ownership and compliance, privacy, intellectual property considerations, compute cost, sustainability issues, and responsible AI requirements.

MedImageInsight: An Open-Source Embedding Model for General Domain Medical Imaging

In this work, we present MedImageInsight, an open-source medical imaging embedding model. MedImageInsight is trained on medical images with associated text and labels across a diverse collection of domains, including X-Ray, CT, MRI, dermoscopy, OCT, fundus photography, ultrasound, histopathology, and mammography. Rigorous evaluations demonstrate MedImageInsight's ability to achieve state-of-the-art (SOTA) or human expert level performance across classification, image-image search, and fine-tuning tasks. Specifically, on public datasets, MedImageInsight achieves SOTA in CT 3D medical image retrieval, as well as SOTA in disease classification and search for chest X-ray, dermatology, and OCT imaging. Furthermore, MedImageInsight achieves human expert performance in bone age estimation (on both public and partner data), as well as AUC above 0.9 in most other domains. When paired with a text decoder, MedImageInsight achieves near SOTA level single image report findings generation with less than 10\% the parameters of other models. Compared to fine-tuning GPT-4o with only MIMIC-CXR data for the same task, MedImageInsight outperforms in clinical metrics, but underperforms on lexical metrics where GPT-4o sets a new SOTA. Importantly for regulatory purposes, MedImageInsight can generate ROC curves, adjust sensitivity and specificity based on clinical need, and provide evidence-based decision support through image-image search (which can also enable retrieval augmented generation). In an independent clinical evaluation of image-image search in chest X-ray, MedImageInsight outperformed every other publicly available foundation model evaluated by large margins (over 6 points AUC), and significantly outperformed other models in terms of AI fairness (across age and gender). We hope releasing MedImageInsight will help enhance collective progress in medical imaging AI research and development.

From Introspection to Best Practices: Principled Analysis of Demonstrations in Multimodal In-Context Learning

Motivated by in-context learning (ICL) capabilities of Large Language models (LLMs), multimodal LLMs with additional visual modality are also exhibited with similar ICL abilities when multiple image-text pairs are provided as demonstrations. However, relatively less work has been done to investigate the principles behind how and why multimodal ICL works. We conduct a systematic and principled evaluation of multimodal ICL for models of different scales on a broad spectrum of new yet critical tasks. Through perturbations over different modality information, we show that modalities matter differently across tasks in multimodal ICL. Considering such modality impact, we further utilize modality-driven demonstration strategies to boost ICL performance. We also identify that demonstration selection is closely related to the models' ability to capture task inductive biases from multimodal ICL. Our principled analysis provides a comprehensive way of understanding the role of demonstrations in multimodal in-context learning, and sheds light on effectively improving multimodal ICL on a wide range of tasks even if those tasks are not seen in or even contradict pretraining data.

mDPO: Conditional Preference Optimization for Multimodal Large Language Models

Direct preference optimization (DPO) has shown to be an effective method for large language model (LLM) alignment. Recent works have attempted to apply DPO to multimodal scenarios but have found it challenging to achieve consistent improvement. Through a comparative experiment, we identify the unconditional preference problem in multimodal preference optimization, where the model overlooks the image condition. To address this problem, we propose mDPO, a multimodal DPO objective that prevents the over-prioritization of language-only preferences by also optimizing image preference. Moreover, we introduce a reward anchor that forces the reward to be positive for chosen responses, thereby avoiding the decrease in their likelihood -- an intrinsic problem of relative preference optimization. Experiments on two multimodal LLMs of different sizes and three widely used benchmarks demonstrate that mDPO effectively addresses the unconditional preference problem in multimodal preference optimization and significantly improves model performance, particularly in reducing hallucination.

MuirBench: A Comprehensive Benchmark for Robust Multi-image Understanding

We introduce MuirBench, a comprehensive benchmark that focuses on robust multi-image understanding capabilities of multimodal LLMs. MuirBench consists of 12 diverse multi-image tasks (e.g., scene understanding, ordering) that involve 10 categories of multi-image relations (e.g., multiview, temporal relations). Comprising 11,264 images and 2,600 multiple-choice questions, MuirBench is created in a pairwise manner, where each standard instance is paired with an unanswerable variant that has minimal semantic differences, in order for a reliable assessment. Evaluated upon 20 recent multi-modal LLMs, our results reveal that even the best-performing models like GPT-4o and Gemini Pro find it challenging to solve MuirBench, achieving 68.0% and 49.3% in accuracy. Open-source multimodal LLMs trained on single images can hardly generalize to multi-image questions, hovering below 33.3% in accuracy. These results highlight the importance of MuirBench in encouraging the community to develop multimodal LLMs that can look beyond a single image, suggesting potential pathways for future improvements.

BiomedParse: a biomedical foundation model for image parsing of everything everywhere all at once

Biomedical image analysis is fundamental for biomedical discovery in cell biology, pathology, radiology, and many other biomedical domains. Holistic image analysis comprises interdependent subtasks such as segmentation, detection, and recognition of relevant objects. Here, we propose BiomedParse, a biomedical foundation model for imaging parsing that can jointly conduct segmentation, detection, and recognition for 82 object types across 9 imaging modalities. Through joint learning, we can improve accuracy for individual tasks and enable novel applications such as segmenting all relevant objects in an image through a text prompt, rather than requiring users to laboriously specify the bounding box for each object. We leveraged readily available natural-language labels or descriptions accompanying those datasets and use GPT-4 to harmonize the noisy, unstructured text information with established biomedical object ontologies. We created a large dataset comprising over six million triples of image, segmentation mask, and textual description. On image segmentation, we showed that BiomedParse is broadly applicable, outperforming state-of-the-art methods on 102,855 test image-mask-label triples across 9 imaging modalities (everything). On object detection, which aims to locate a specific object of interest, BiomedParse again attained state-of-the-art performance, especially on objects with irregular shapes (everywhere). On object recognition, which aims to identify all objects in a given image along with their semantic types, we showed that BiomedParse can simultaneously segment and label all biomedical objects in an image (all at once). In summary, BiomedParse is an all-in-one tool for biomedical image analysis by jointly solving segmentation, detection, and recognition for all major biomedical image modalities, paving the path for efficient and accurate image-based biomedical discovery.

Offset Unlearning for Large Language Models

Despite the strong capabilities of Large Language Models (LLMs) to acquire knowledge from their training corpora, the memorization of sensitive information in the corpora such as copyrighted, harmful, and private content has led to ethical and legal concerns. In response to these challenges, unlearning has emerged as a potential remedy for LLMs affected by problematic training data. However, previous unlearning techniques are either not applicable to black-box LLMs due to required access to model internal weights, or violate data protection principles by retaining sensitive data for inference-time correction. We propose $\delta$-unlearning, an offset unlearning framework for black-box LLMs. Instead of tuning the black-box LLM itself, $\delta$-unlearning learns the logit offset needed for unlearning by contrasting the logits from a pair of smaller models. Experiments demonstrate that $\delta$-unlearning can effectively unlearn target data while maintaining similar or even stronger performance on general out-of-forget-scope tasks. $\delta$-unlearning also effectively incorporates different unlearning algorithms, making our approach a versatile solution to adapting various existing unlearning algorithms to black-box LLMs.

Training Small Multimodal Models to Bridge Biomedical Competency Gap: A Case Study in Radiology Imaging

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such large models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world applications. Frontier models such as GPT-4V still have major competency gaps in multimodal capabilities for biomedical applications. Moreover, pragmatic issues such as access, cost, latency, and compliance make it hard for clinicians to use privately-hosted state-of-the-art large models directly on private patient data. In this paper, we explore training open-source small multimodal models (SMMs) to bridge biomedical competency gaps for unmet clinical needs. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space. We conduct a comprehensive study of this approach on radiology imaging. For training, we assemble a large dataset with over 1 million image-text pairs. For evaluation, we propose a clinically driven novel approach using GPT-4 and demonstrate its parity with expert evaluation. We also study grounding qualitatively using attention. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LLaVA-Rad (7B) model attains state-of-the-art results on radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). LLaVA-Rad is fast and can be run on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

Attribute Structuring Improves LLM-Based Evaluation of Clinical Text Summaries

Summarizing clinical text is crucial in health decision-support and clinical research. Large language models (LLMs) have shown the potential to generate accurate clinical text summaries, but still struggle with issues regarding grounding and evaluation, especially in safety-critical domains such as health. Holistically evaluating text summaries is challenging because they may contain unsubstantiated information. Here, we explore a general mitigation framework using Attribute Structuring (AS), which structures the summary evaluation process. It decomposes the evaluation process into a grounded procedure that uses an LLM for relatively simple structuring and scoring tasks, rather than the full task of holistic summary evaluation. Experiments show that AS consistently improves the correspondence between human annotations and automated metrics in clinical text summarization. Additionally, AS yields interpretations in the form of a short text span corresponding to each output, which enables efficient human auditing, paving the way towards trustworthy evaluation of clinical information in resource-constrained scenarios. We release our code, prompts, and an open-source benchmark at https://github.com/microsoft/attribute-structuring.

T-Rex: Text-assisted Retrosynthesis Prediction

As a fundamental task in computational chemistry, retrosynthesis prediction aims to identify a set of reactants to synthesize a target molecule. Existing template-free approaches only consider the graph structures of the target molecule, which often cannot generalize well to rare reaction types and large molecules. Here, we propose T-Rex, a text-assisted retrosynthesis prediction approach that exploits pre-trained text language models, such as ChatGPT, to assist the generation of reactants. T-Rex first exploits ChatGPT to generate a description for the target molecule and rank candidate reaction centers based both the description and the molecular graph. It then re-ranks these candidates by querying the descriptions for each reactants and examines which group of reactants can best synthesize the target molecule. We observed that T-Rex substantially outperformed graph-based state-of-the-art approaches on two datasets, indicating the effectiveness of considering text information. We further found that T-Rex outperformed the variant that only use ChatGPT-based description without the re-ranking step, demonstrate how our framework outperformed a straightforward integration of ChatGPT and graph information. Collectively, we show that text generated by pre-trained language models can substantially improve retrosynthesis prediction, opening up new avenues for exploiting ChatGPT to advance computational chemistry. And the codes can be found at https://github.com/lauyikfung/T-Rex.