PathAlign: A vision-language model for whole slide images in histopathology

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

Can Few-shot Work in Long-Context? Recycling the Context to Generate Demonstrations

Despite recent advancements in Large Language Models (LLMs), their performance on tasks involving long contexts remains sub-optimal. In-Context Learning (ICL) with few-shot examples may be an appealing solution to enhance LLM performance in this scenario; However, naively adding ICL examples with long context introduces challenges, including substantial token overhead added for each few-shot example and context mismatch between the demonstrations and the target query. In this work, we propose to automatically generate few-shot examples for long context QA tasks by recycling contexts. Specifically, given a long input context (1-3k tokens) and a query, we generate additional query-output pairs from the given context as few-shot examples, while introducing the context only once. This ensures that the demonstrations are leveraging the same context as the target query while only adding a small number of tokens to the prompt. We further enhance each demonstration by instructing the model to explicitly identify the relevant paragraphs before the answer, which improves performance while providing fine-grained attribution to the answer source. We apply our method on multiple LLMs and obtain substantial improvements on various QA datasets with long context, especially when the answer lies within the middle of the context. Surprisingly, despite introducing only single-hop ICL examples, LLMs also successfully generalize to multi-hop long-context QA using our approach.

Towards a Personal Health Large Language Model

In health, most large language model (LLM) research has focused on clinical tasks. However, mobile and wearable devices, which are rarely integrated into such tasks, provide rich, longitudinal data for personal health monitoring. Here we present Personal Health Large Language Model (PH-LLM), fine-tuned from Gemini for understanding and reasoning over numerical time-series personal health data. We created and curated three datasets that test 1) production of personalized insights and recommendations from sleep patterns, physical activity, and physiological responses, 2) expert domain knowledge, and 3) prediction of self-reported sleep outcomes. For the first task we designed 857 case studies in collaboration with domain experts to assess real-world scenarios in sleep and fitness. Through comprehensive evaluation of domain-specific rubrics, we observed that Gemini Ultra 1.0 and PH-LLM are not statistically different from expert performance in fitness and, while experts remain superior for sleep, fine-tuning PH-LLM provided significant improvements in using relevant domain knowledge and personalizing information for sleep insights. We evaluated PH-LLM domain knowledge using multiple choice sleep medicine and fitness examinations. PH-LLM achieved 79% on sleep and 88% on fitness, exceeding average scores from a sample of human experts. Finally, we trained PH-LLM to predict self-reported sleep quality outcomes from textual and multimodal encoding representations of wearable data, and demonstrate that multimodal encoding is required to match performance of specialized discriminative models. Although further development and evaluation are necessary in the safety-critical personal health domain, these results demonstrate both the broad knowledge and capabilities of Gemini models and the benefit of contextualizing physiological data for personal health applications as done with PH-LLM.

Multi-turn Reinforcement Learning from Preference Human Feedback

Reinforcement Learning from Human Feedback (RLHF) has become the standard approach for aligning Large Language Models (LLMs) with human preferences, allowing LLMs to demonstrate remarkable abilities in various tasks. Existing methods work by emulating the preferences at the single decision (turn) level, limiting their capabilities in settings that require planning or multi-turn interactions to achieve a long-term goal. In this paper, we address this issue by developing novel methods for Reinforcement Learning (RL) from preference feedback between two full multi-turn conversations. In the tabular setting, we present a novel mirror-descent-based policy optimization algorithm for the general multi-turn preference-based RL problem, and prove its convergence to Nash equilibrium. To evaluate performance, we create a new environment, Education Dialogue, where a teacher agent guides a student in learning a random topic, and show that a deep RL variant of our algorithm outperforms RLHF baselines. Finally, we show that in an environment with explicit rewards, our algorithm recovers the same performance as a reward-based RL baseline, despite relying solely on a weaker preference signal.

Advancing Multimodal Medical Capabilities of Gemini

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

Capabilities of Gemini Models in Medicine

Excellence in a wide variety of medical applications poses considerable challenges for AI, requiring advanced reasoning, access to up-to-date medical knowledge and understanding of complex multimodal data. Gemini models, with strong general capabilities in multimodal and long-context reasoning, offer exciting possibilities in medicine. Building on these core strengths of Gemini, we introduce Med-Gemini, a family of highly capable multimodal models that are specialized in medicine with the ability to seamlessly use web search, and that can be efficiently tailored to novel modalities using custom encoders. We evaluate Med-Gemini on 14 medical benchmarks, establishing new state-of-the-art (SoTA) performance on 10 of them, and surpass the GPT-4 model family on every benchmark where a direct comparison is viable, often by a wide margin. On the popular MedQA (USMLE) benchmark, our best-performing Med-Gemini model achieves SoTA performance of 91.1% accuracy, using a novel uncertainty-guided search strategy. On 7 multimodal benchmarks including NEJM Image Challenges and MMMU (health & medicine), Med-Gemini improves over GPT-4V by an average relative margin of 44.5%. We demonstrate the effectiveness of Med-Gemini's long-context capabilities through SoTA performance on a needle-in-a-haystack retrieval task from long de-identified health records and medical video question answering, surpassing prior bespoke methods using only in-context learning. Finally, Med-Gemini's performance suggests real-world utility by surpassing human experts on tasks such as medical text summarization, alongside demonstrations of promising potential for multimodal medical dialogue, medical research and education. Taken together, our results offer compelling evidence for Med-Gemini's potential, although further rigorous evaluation will be crucial before real-world deployment in this safety-critical domain.

A Toolbox for Surfacing Health Equity Harms and Biases in Large Language Models

Large language models (LLMs) hold immense promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. In this work, we present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, surfaces biases that may be missed via narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all.

Breaking the Language Barrier: Can Direct Inference Outperform Pre-Translation in Multilingual LLM Applications?

Large language models hold significant promise in multilingual applications. However, inherent biases stemming from predominantly English-centric pre-training have led to the widespread practice of pre-translation, i.e., translating non-English inputs to English before inference, leading to complexity and information loss. This study re-evaluates the need for pre-translation in the context of PaLM2 models (Anil et al., 2023), which have been established as highly performant in multilingual tasks. We offer a comprehensive investigation across 108 languages and 6 diverse benchmarks, including open-end generative tasks, which were excluded from previous similar studies. Our findings challenge the pre-translation paradigm established in prior research, highlighting the advantages of direct inference in PaLM2. Specifically, PaLM2-L consistently outperforms pre-translation in 94 out of 108 languages. These findings pave the way for more efficient and effective multilingual applications, alleviating the limitations associated with pre-translation and unlocking linguistic authenticity.

HeAR -- Health Acoustic Representations

Health acoustic sounds such as coughs and breaths are known to contain useful health signals with significant potential for monitoring health and disease, yet are underexplored in the medical machine learning community. The existing deep learning systems for health acoustics are often narrowly trained and evaluated on a single task, which is limited by data and may hinder generalization to other tasks. To mitigate these gaps, we develop HeAR, a scalable self-supervised learning-based deep learning system using masked autoencoders trained on a large dataset of 313 million two-second long audio clips. Through linear probes, we establish HeAR as a state-of-the-art health audio embedding model on a benchmark of 33 health acoustic tasks across 6 datasets. By introducing this work, we hope to enable and accelerate further health acoustics research.

Closing the AI generalization gap by adjusting for dermatology condition distribution differences across clinical settings

Recently, there has been great progress in the ability of artificial intelligence (AI) algorithms to classify dermatological conditions from clinical photographs. However, little is known about the robustness of these algorithms in real-world settings where several factors can lead to a loss of generalizability. Understanding and overcoming these limitations will permit the development of generalizable AI that can aid in the diagnosis of skin conditions across a variety of clinical settings. In this retrospective study, we demonstrate that differences in skin condition distribution, rather than in demographics or image capture mode are the main source of errors when an AI algorithm is evaluated on data from a previously unseen source. We demonstrate a series of steps to close this generalization gap, requiring progressively more information about the new source, ranging from the condition distribution to training data enriched for data less frequently seen during training. Our results also suggest comparable performance from end-to-end fine tuning versus fine tuning solely the classification layer on top of a frozen embedding model. Our approach can inform the adaptation of AI algorithms to new settings, based on the information and resources available.