S. Sara Mahdavi

Chitwan Saharia, William Chan, Saurabh Saxena et al. · deepmind

We present Imagen, a text-to-image diffusion model with an unprecedented degree of photorealism and a deep level of language understanding. Imagen builds on the power of large transformer language models in understanding text and hinges on the strength of diffusion models in high-fidelity image generation. Our key discovery is that generic large language models (e.g. T5), pretrained on text-only corpora, are surprisingly effective at encoding text for image synthesis: increasing the size of the language model in Imagen boosts both sample fidelity and image-text alignment much more than increasing the size of the image diffusion model. Imagen achieves a new state-of-the-art FID score of 7.27 on the COCO dataset, without ever training on COCO, and human raters find Imagen samples to be on par with the COCO data itself in image-text alignment. To assess text-to-image models in greater depth, we introduce DrawBench, a comprehensive and challenging benchmark for text-to-image models. With DrawBench, we compare Imagen with recent methods including VQ-GAN+CLIP, Latent Diffusion Models, and DALL-E 2, and find that human raters prefer Imagen over other models in side-by-side comparisons, both in terms of sample quality and image-text alignment. See https://imagen.research.google/ for an overview of the results.

Karan Singhal, Shekoofeh Azizi, Tao Tu et al.

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

Tao Tu, Shekoofeh Azizi, Danny Driess et al.

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

Shekoofeh Azizi, Laura Culp, Jan Freyberg et al.

Recent progress in Medical Artificial Intelligence (AI) has delivered systems that can reach clinical expert level performance. However, such systems tend to demonstrate sub-optimal "out-of-distribution" performance when evaluated in clinical settings different from the training environment. A common mitigation strategy is to develop separate systems for each clinical setting using site-specific data [1]. However, this quickly becomes impractical as medical data is time-consuming to acquire and expensive to annotate [2]. Thus, the problem of "data-efficient generalization" presents an ongoing difficulty for Medical AI development. Although progress in representation learning shows promise, their benefits have not been rigorously studied, specifically for out-of-distribution settings. To meet these challenges, we present REMEDIS, a unified representation learning strategy to improve robustness and data-efficiency of medical imaging AI. REMEDIS uses a generic combination of large-scale supervised transfer learning with self-supervised learning and requires little task-specific customization. We study a diverse range of medical imaging tasks and simulate three realistic application scenarios using retrospective data. REMEDIS exhibits significantly improved in-distribution performance with up to 11.5% relative improvement in diagnostic accuracy over a strong supervised baseline. More importantly, our strategy leads to strong data-efficient generalization of medical imaging AI, matching strong supervised baselines using between 1% to 33% of retraining data across tasks. These results suggest that REMEDIS can significantly accelerate the life-cycle of medical imaging AI development thereby presenting an important step forward for medical imaging AI to deliver broad impact.

Daniel McDuff, Mike Schaekermann, Tao Tu et al.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Ryutaro Tanno, David G. T. Barrett, Andrew Sellergren et al.

Radiology reports are an instrumental part of modern medicine, informing key clinical decisions such as diagnosis and treatment. The worldwide shortage of radiologists, however, restricts access to expert care and imposes heavy workloads, contributing to avoidable errors and delays in report delivery. While recent progress in automated report generation with vision-language models offer clear potential in ameliorating the situation, the path to real-world adoption has been stymied by the challenge of evaluating the clinical quality of AI-generated reports. In this study, we build a state-of-the-art report generation system for chest radiographs, $\textit{Flamingo-CXR}$, by fine-tuning a well-known vision-language foundation model on radiology data. To evaluate the quality of the AI-generated reports, a group of 16 certified radiologists provide detailed evaluations of AI-generated and human written reports for chest X-rays from an intensive care setting in the United States and an inpatient setting in India. At least one radiologist (out of two per case) preferred the AI report to the ground truth report in over 60$\%$ of cases for both datasets. Amongst the subset of AI-generated reports that contain errors, the most frequently cited reasons were related to the location and finding, whereas for human written reports, most mistakes were related to severity and finding. This disparity suggested potential complementarity between our AI system and human experts, prompting us to develop an assistive scenario in which Flamingo-CXR generates a first-draft report, which is subsequently revised by a clinician. This is the first demonstration of clinician-AI collaboration for report writing, and the resultant reports are assessed to be equivalent or preferred by at least one radiologist to reports written by experts alone in 80$\%$ of in-patient cases and 60$\%$ of intensive care cases.

Khaled Saab, Tao Tu, Wei-Hung Weng et al.

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.

Tao Tu, Anil Palepu, Mike Schaekermann et al.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

Khaled Saab, Jan Freyberg, Chunjong Park et al.

Large Language Models (LLMs) have demonstrated great potential for conducting diagnostic conversations but evaluation has been largely limited to language-only interactions, deviating from the real-world requirements of remote care delivery. Instant messaging platforms permit clinicians and patients to upload and discuss multimodal medical artifacts seamlessly in medical consultation, but the ability of LLMs to reason over such data while preserving other attributes of competent diagnostic conversation remains unknown. Here we advance the conversational diagnosis and management performance of the Articulate Medical Intelligence Explorer (AMIE) through a new capability to gather and interpret multimodal data, and reason about this precisely during consultations. Leveraging Gemini 2.0 Flash, our system implements a state-aware dialogue framework, where conversation flow is dynamically controlled by intermediate model outputs reflecting patient states and evolving diagnoses. Follow-up questions are strategically directed by uncertainty in such patient states, leading to a more structured multimodal history-taking process that emulates experienced clinicians. We compared AMIE to primary care physicians (PCPs) in a randomized, blinded, OSCE-style study of chat-based consultations with patient actors. We constructed 105 evaluation scenarios using artifacts like smartphone skin photos, ECGs, and PDFs of clinical documents across diverse conditions and demographics. Our rubric assessed multimodal capabilities and other clinically meaningful axes like history-taking, diagnostic accuracy, management reasoning, communication, and empathy. Specialist evaluation showed AMIE to be superior to PCPs on 7/9 multimodal and 29/32 non-multimodal axes (including diagnostic accuracy). The results show clear progress in multimodal conversational diagnostic AI, but real-world translation needs further research.

Anil Palepu, Vikram Dhillon, Polly Niravath et al.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Elahe Vedadi, David Barrett, Natalie Harris et al.

Recent work has demonstrated the promise of conversational AI systems for diagnostic dialogue. However, real-world assurance of patient safety means that providing individual diagnoses and treatment plans is considered a regulated activity by licensed professionals. Furthermore, physicians commonly oversee other team members in such activities, including nurse practitioners (NPs) or physician assistants/associates (PAs). Inspired by this, we propose a framework for effective, asynchronous oversight of the Articulate Medical Intelligence Explorer (AMIE) AI system. We propose guardrailed-AMIE (g-AMIE), a multi-agent system that performs history taking within guardrails, abstaining from individualized medical advice. Afterwards, g-AMIE conveys assessments to an overseeing primary care physician (PCP) in a clinician cockpit interface. The PCP provides oversight and retains accountability of the clinical decision. This effectively decouples oversight from intake and can thus happen asynchronously. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) of text consultations with asynchronous oversight, we compared g-AMIE to NPs/PAs or a group of PCPs under the same guardrails. Across 60 scenarios, g-AMIE outperformed both groups in performing high-quality intake, summarizing cases, and proposing diagnoses and management plans for the overseeing PCP to review. This resulted in higher quality composite decisions. PCP oversight of g-AMIE was also more time-efficient than standalone PCP consultations in prior work. While our study does not replicate existing clinical practices and likely underestimates clinicians' capabilities, our results demonstrate the promise of asynchronous oversight as a feasible paradigm for diagnostic AI systems to operate under expert human oversight for enhancing real-world care.

Juan Manuel Zambrano Chaves, Eric Wang, Tao Tu et al.

Developing therapeutics is a lengthy and expensive process that requires the satisfaction of many different criteria, and AI models capable of expediting the process would be invaluable. However, the majority of current AI approaches address only a narrowly defined set of tasks, often circumscribed within a particular domain. To bridge this gap, we introduce Tx-LLM, a generalist large language model (LLM) fine-tuned from PaLM-2 which encodes knowledge about diverse therapeutic modalities. Tx-LLM is trained using a collection of 709 datasets that target 66 tasks spanning various stages of the drug discovery pipeline. Using a single set of weights, Tx-LLM simultaneously processes a wide variety of chemical or biological entities(small molecules, proteins, nucleic acids, cell lines, diseases) interleaved with free-text, allowing it to predict a broad range of associated properties, achieving competitive with state-of-the-art (SOTA) performance on 43 out of 66 tasks and exceeding SOTA on 22. Among these, Tx-LLM is particularly powerful and exceeds best-in-class performance on average for tasks combining molecular SMILES representations with text such as cell line names or disease names, likely due to context learned during pretraining. We observe evidence of positive transfer between tasks with diverse drug types (e.g.,tasks involving small molecules and tasks involving proteins), and we study the impact of model size, domain finetuning, and prompting strategies on performance. We believe Tx-LLM represents an important step towards LLMs encoding biochemical knowledge and could have a future role as an end-to-end tool across the drug discovery development pipeline.

Karan Singhal, Tao Tu, Juraj Gottweis et al.

Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.

Tajwar Abrar Aleef, Ingrid T. Spadinger, Michael D. Peacock et al.

Treatment planning in low-dose-rate prostate brachytherapy (LDR-PB) aims to produce arrangement of implantable radioactive seeds that deliver a minimum prescribed dose to the prostate whilst minimizing toxicity to healthy tissues. There can be multiple seed arrangements that satisfy this dosimetric criterion, not all deemed 'acceptable' for implant from a physician's perspective. This leads to plans that are subjective to the physician's/centre's preference, planning style, and expertise. We propose a method that aims to reduce this variability by training a model to learn from a large pool of successful retrospective LDR-PB data (961 patients) and create consistent plans that mimic the high-quality manual plans. Our model is based on conditional generative adversarial networks that use a novel loss function for penalizing the model on spatial constraints of the seeds. An optional optimizer based on a simulated annealing (SA) algorithm can be used to further fine-tune the plans if necessary (determined by the treating physician). Performance analysis was conducted on 150 test cases demonstrating comparable results to that of the manual prehistorical plans. On average, the clinical target volume covering 100% of the prescribed dose was 98.9% for our method compared to 99.4% for manual plans. Moreover, using our model, the planning time was significantly reduced to an average of 2.5 mins/plan with SA, and less than 3 seconds without SA. Compared to this, manual planning at our centre takes around 20 mins/plan.