Yun Liu
Yun is a senior staff research scientist in Google Research. In this role he focuses on developing and validating machine learning for medical applications across multiple fields: pathology, ophthalmology, radiology, dermatology, and more. Yun completed his PhD at Harvard-MIT Health Sciences and Technology, where he worked on predictive risk modeling using biomedical signals, medical text, and billing codes. He has previously also worked on predictive modeling for nucleic acid sequences and protein structures. Yun completed a B.S. in Molecular and Cellular Biology and Computer Science at Johns Hopkins University.
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A Toolbox for Surfacing Health Equity Harms and Biases in Large Language Models
Heather Cole-Lewis
Nenad Tomašev
Liam McCoy
Leo Anthony Celi
Alanna Walton
Akeiylah DeWitt
Philip Mansfield
Sushant Prakash
Joelle Barral
Ivor Horn
Karan Singhal
Arxiv(2024) (to appear)
Preview abstract
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.
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Health equity assessment of machine learning performance (HEAL): a framework and dermatology AI model case study
Terry Spitz
Malcolm Chelliah
Heather Cole-Lewis
Stephanie Farquhar
Qinghan Xue
Jenna Lester
Cían Hughes
Patricia Strachan
Fraser Tan
Peggy Bui
Craig Mermel
Lily Peng
Sunny Virmani
Ivor Horn
Cameron Chen
The Lancet eClinicalMedicine(2024)
Preview abstract
Background
Artificial intelligence (AI) has repeatedly been shown to encode historical inequities in healthcare. We aimed to develop a framework to quantitatively assess the performance equity of health AI technologies and to illustrate its utility via a case study.
Methods
Here, we propose a methodology to assess whether health AI technologies prioritise performance for patient populations experiencing worse outcomes, that is complementary to existing fairness metrics. We developed the Health Equity Assessment of machine Learning performance (HEAL) framework designed to quantitatively assess the performance equity of health AI technologies via a four-step interdisciplinary process to understand and quantify domain-specific criteria, and the resulting HEAL metric. As an illustrative case study (analysis conducted between October 2022 and January 2023), we applied the HEAL framework to a dermatology AI model. A set of 5420 teledermatology cases (store-and-forward cases from patients of 20 years or older, submitted from primary care providers in the USA and skin cancer clinics in Australia), enriched for diversity in age, sex and race/ethnicity, was used to retrospectively evaluate the AI model's HEAL metric, defined as the likelihood that the AI model performs better for subpopulations with worse average health outcomes as compared to others. The likelihood that AI performance was anticorrelated to pre-existing health outcomes was estimated using bootstrap methods as the probability that the negated Spearman's rank correlation coefficient (i.e., “R”) was greater than zero. Positive values of R suggest that subpopulations with poorer health outcomes have better AI model performance. Thus, the HEAL metric, defined as p (R >0), measures how likely the AI technology is to prioritise performance for subpopulations with worse average health outcomes as compared to others (presented as a percentage below). Health outcomes were quantified as disability-adjusted life years (DALYs) when grouping by sex and age, and years of life lost (YLLs) when grouping by race/ethnicity. AI performance was measured as top-3 agreement with the reference diagnosis from a panel of 3 dermatologists per case.
Findings
Across all dermatologic conditions, the HEAL metric was 80.5% for prioritizing AI performance of racial/ethnic subpopulations based on YLLs, and 92.1% and 0.0% respectively for prioritizing AI performance of sex and age subpopulations based on DALYs. Certain dermatologic conditions were significantly associated with greater AI model performance compared to a reference category of less common conditions. For skin cancer conditions, the HEAL metric was 73.8% for prioritizing AI performance of age subpopulations based on DALYs.
Interpretation
Analysis using the proposed HEAL framework showed that the dermatology AI model prioritised performance for race/ethnicity, sex (all conditions) and age (cancer conditions) subpopulations with respect to pre-existing health disparities. More work is needed to investigate ways of promoting equitable AI performance across age for non-cancer conditions and to better understand how AI models can contribute towards improving equity in health outcomes.
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An intentional approach to managing bias in embedding models
Atilla P. Kiraly
Jungyeon Park
Rory Pilgrim
Charles Lau
Heather Cole-Lewis
Shravya Shetty
Krish Eswaran
Leo Anthony Celi
The Lancet Digital Health, 6(2024), E126-E130
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Advances in machine learning for health care have brought concerns about bias from the research community; specifically, the introduction, perpetuation, or exacerbation of care disparities. Reinforcing these concerns is the finding that medical images often reveal signals about sensitive attributes in ways that are hard to pinpoint by both algorithms and people. This finding raises a question about how to best design general purpose pretrained embeddings (GPPEs, defined as embeddings meant to support a broad array of use cases) for building downstream models that are free from particular types of bias. The downstream model should be carefully evaluated for bias, and audited and improved as appropriate. However, in our view, well intentioned attempts to prevent the upstream components—GPPEs—from learning sensitive attributes can have unintended consequences on the downstream models. Despite producing a veneer of technical neutrality, the resultant end-to-end system might still be biased or poorly performing. We present reasons, by building on previously published data, to support the reasoning that GPPEs should ideally contain as much information as the original data contain, and highlight the perils of trying to remove sensitive attributes from a GPPE. We also emphasise that downstream prediction models trained for specific tasks and settings, whether developed using GPPEs or not, should be carefully designed and evaluated to avoid bias that makes models vulnerable to issues such as distributional shift. These evaluations should be done by a diverse team, including social scientists, on a diverse cohort representing the full breadth of the patient population for which the final model is intended.
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Towards Generalist Biomedical AI
Danny Driess
Andrew Carroll
Chuck Lau
Ryutaro Tanno
Ira Ktena
Anil Palepu
Basil Mustafa
Aakanksha Chowdhery
Simon Kornblith
Philip Mansfield
Sushant Prakash
Renee Wong
Sunny Virmani
Sara Mahdavi
Bradley Green
Ewa Dominowska
Joelle Barral
Karan Singhal
Pete Florence
NEJM AI(2024)
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BACKGROUND: Medicine is inherently multimodal, requiring the simultaneous interpretation and integration of insights between many data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence systems that flexibly encode, integrate, and interpret these data might better enable impactful applications ranging from scientific discovery to care delivery.
METHODS: To catalyze development of these models, we curated 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 introduced Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. To further probe the capabilities and limitations of Med-PaLM M, we conducted a radiologist evaluation of model-generated (and human) chest x-ray reports.
RESULTS: We observed encouraging performance across model scales. Med-PaLM M reached performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. In a side-by-side ranking on 246 retrospective chest x-rays, clinicians expressed a pairwise preference for Med-PaLM Multimodal reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility.
CONCLUSIONS: Although considerable work is needed to validate these models in real-world cases and understand if cross-modality generalization is possible, our results represent a milestone toward the development of generalist biomedical artificial intelligence systems.
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Predicting Cardiovascular Disease Risk using Photoplethysmography and Deep Learning
Sebastien Baur
Christina Chen
Mariam Jabara
Babak Behsaz
Shravya Shetty
Goodarz Danaei
Diego Ardila
PLOS Glob Public Health, 4(6)(2024), e0003204
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Cardiovascular diseases (CVDs) are responsible for a large proportion of premature deaths in low- and middle-income countries. Early CVD detection and intervention is critical in these populations, yet many existing CVD risk scores require a physical examination or lab measurements, which can be challenging in such health systems due to limited accessibility. We investigated the potential to use photoplethysmography (PPG), a sensing technology available on most smartphones that can potentially enable large-scale screening at low cost, for CVD risk prediction. We developed a deep learning PPG-based CVD risk score (DLS) to predict the probability of having major adverse cardiovascular events (MACE: non-fatal myocardial infarction, stroke, and cardiovascular death) within ten years, given only age, sex, smoking status and PPG as predictors. We compare the DLS with the office-based refit-WHO score, which adopts the shared predictors from WHO and Globorisk scores (age, sex, smoking status, height, weight and systolic blood pressure) but refitted on the UK Biobank (UKB) cohort. All models were trained on a development dataset (141,509 participants) and evaluated on a geographically separate test (54,856 participants) dataset, both from UKB. DLS’s C-statistic (71.1%, 95% CI 69.9–72.4) is non-inferior to office-based refit-WHO score (70.9%, 95% CI 69.7–72.2; non-inferiority margin of 2.5%, p<0.01) in the test dataset. The calibration of the DLS is satisfactory, with a 1.8% mean absolute calibration error. Adding DLS features to the office-based score increases the C-statistic by 1.0% (95% CI 0.6–1.4). DLS predicts ten-year MACE risk comparable with the office-based refit-WHO score. Interpretability analyses suggest that the DLS-extracted features are related to PPG waveform morphology and are independent of heart rate. Our study provides a proof-of-concept and suggests the potential of a PPG-based approach strategies for community-based primary prevention in resource-limited regions.
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Conversational AI in health: Design considerations from a Wizard-of-Oz dermatology case study with users, clinicians and a medical LLM
Brenna Li
Amy Wang
Patricia Strachan
Julie Anne Seguin
Sami Lachgar
Karyn Schroeder
Renee Wong
Extended Abstracts of the 2024 CHI Conference on Human Factors in Computing Systems, Association for Computing Machinery, pp. 10
Preview abstract
Although skin concerns are common, access to specialist care is limited. Artificial intelligence (AI)-assisted tools to support medical decisions may provide patients with feedback on their concerns while also helping ensure the most urgent cases are routed to dermatologists. Although AI-based conversational agents have been explored recently, how they are perceived by patients and clinicians is not well understood. We conducted a Wizard-of-Oz study involving 18 participants with real skin concerns. Participants were randomly assigned to interact with either a clinician agent (portrayed by a dermatologist) or an LLM agent (supervised by a dermatologist) via synchronous multimodal chat. In both conditions, participants found the conversation to be helpful in understanding their medical situation and alleviate their concerns. Through qualitative coding of the conversation transcripts, we provide insight on the importance of empathy and effective information-seeking. We conclude with design considerations for future AI-based conversational agents in healthcare settings.
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Differences between Patient and Clinician Submitted Images: Implications for Virtual Care of Skin Conditions
Rajeev Rikhye
Grace Eunhae Hong
Margaret Ann Smith
Aaron Loh
Vijaytha Muralidharan
Doris Wong
Michelle Phung
Nicolas Betancourt
Bradley Fong
Rachna Sahasrabudhe
Khoban Nasim
Alec Eschholz
Kat Chou
Peggy Bui
Justin Ko
Steven Lin
Mayo Clinic Proceedings: Digital Health(2024)
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Objective: To understand and highlight the differences in clinical, demographic, and image quality characteristics between patient-taken (PAT) and clinic-taken (CLIN) photographs of skin conditions.
Patients and Methods: This retrospective study applied logistic regression to data from 2500 deidentified cases in Stanford Health Care’s eConsult system, from November 2015 to January 2021. Cases with undiagnosable or multiple conditions or cases with both patient and clinician image sources were excluded, leaving 628 PAT cases and 1719 CLIN cases. Demographic characteristic factors, such as age and sex were self-reported, whereas anatomic location, estimated skin type, clinical signs and symptoms, condition duration, and condition frequency were summarized from patient health records. Image quality variables such as blur, lighting issues and whether the image contained skin, hair, or nails were estimated through a deep learning model.
Results: Factors that were positively associated with CLIN photographs, post-2020 were as follows: age 60 years or older, darker skin types (eFST V/VI), and presence of skin growths. By contrast, factors that were positively associated with PAT photographs include conditions appearing intermittently, cases with blurry photographs, photographs with substantial nonskin (or nail/hair) regions and cases with more than 3 photographs. Within the PAT cohort, older age was associated with blurry photographs.
Conclusion: There are various demographic, clinical, and image quality characteristic differences between PAT and CLIN photographs of skin concerns. The demographic characteristic differences present important considerations for improving digital literacy or access, whereas the image quality differences point to the need for improved patient education and better image capture workflows, particularly among elderly patients.
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Assistive AI in Lung Cancer Screening: A Retrospective Multinational Study in the United States and Japan
Atilla Kiraly
Corbin Cunningham
Ryan Najafi
Jie Yang
Chuck Lau
Diego Ardila
Scott Mayer McKinney
Rory Pilgrim
Mozziyar Etemadi
Sunny Jansen
Lily Peng
Shravya Shetty
Neeral Beladia
Krish Eswaran
Radiology: Artificial Intelligence(2024)
Preview abstract
Lung cancer is the leading cause of cancer death world-wide with 1.8 million deaths in 20201. Studies have concluded that low-dose computed tomography lung cancer screening can reduce mortality by up to 61%2 and updated 2021 US guidelines expanded eligibility. As screening efforts rise, AI can play an important role, but must be unobtrusively integrated into existing clinical workflows. In this work, we introduce a state-of-the-art, cloud-based AI system providing lung cancer risk assessments without requiring any user input. We demonstrate its efficacy in assisting lung cancer screening under both US and Japanese screening settings using different patient populations and screening protocols. Technical improvements over a previously described system include a focus on earlier cancer detection for improved accuracy, introduction of an effective assistive user interface, and a system designed to integrate into typical clinical workflows. The stand-alone AI system was evaluated on 3085 individuals achieving area under the curve (AUC) scores of 91.7% (95%CI [89.6, 95.2]), 93.3% (95%CI [90.2, 95.7]), and 89.1% (95%CI [77.7, 97.3]) on three datasets (two from US and one from Japan), respectively. To evaluate the system’s assistive ability, we conducted two retrospective multi-reader multi-case studies on 627 cases read by experienced board certified radiologists (average 20 years of experience [7,40]) using local PACS systems in the respective US and Japanese screening settings. The studies measured the reader’s level of suspicion (LoS) and categorical responses for scores and management recommendations under country-specific screening protocols. The radiologists’ AUC for LoS increased with AI assistance by 2.3% (95%CI [0.1-4.5], p=0.022) for the US study and by 2.3% (95%CI [-3.5-8.1], p=0.179) for the Japan study. Specificity for recalls increased by 5.5% (95%CI [2.7-8.5], p<0.0001) for the US and 6.7% (95%CI [4.7-8.7], p<0.0001) for the Japan study. No significant reduction in other metrics occured. This work advances the state-of-the-art in lung cancer detection, introduces generalizable interface concepts that can be applicable to similar AI applications, and demonstrates its potential impact on diagnostic AI in global lung cancer screening with results suggesting a substantial drop in unnecessary follow-up procedures without impacting sensitivity.
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Predicting lymph node metastasis from primary tumor histology and clinicopathologic factors in colorectal cancer using deep learning
Fraser Tan
Isabelle Flament-Auvigne
Trissia Brown
Markus Plass
Robert Reihs
Heimo Mueller
Kurt Zatloukal
Pema Richeson
Lily Peng
Craig Mermel
Cameron Chen
Saurabh Gombar
Thomas Montine
Jeanne Shen
Nature Communications Medicine, 3(2023), pp. 59
Preview abstract
Background: Presence of lymph node metastasis (LNM) influences prognosis and clinical decision-making in colorectal cancer. However, detection of LNM is variable and depends on a number of external factors. Deep learning has shown success in computational pathology, but has struggled to boost performance when combined with known predictors.
Methods: Machine-learned features are created by clustering deep learning embeddings of small patches of tumor in colorectal cancer via k-means, and then selecting the top clusters that add predictive value to a logistic regression model when combined with known baseline clinicopathological variables. We then analyze performance of logistic regression models trained with and without these machine-learned features in combination with the baseline variables.
Results: The machine-learned extracted features provide independent signal for the presence of LNM (AUROC: 0.638, 95% CI: [0.590, 0.683]). Furthermore, the machine-learned features add predictive value to the set of 6 clinicopathologic variables in an external validation set (likelihood ratio test, p < 0.00032; AUROC: 0.740, 95% CI: [0.701, 0.780]). A model incorporating these features can also further risk-stratify patients with and without identified metastasis (p < 0.001 for both stage II and stage III).
Conclusion: This work demonstrates an effective approach to combine deep learning with established clinicopathologic factors in order to identify independently informative features associated with LNM. Further work building on these specific results may have important impact in prognostication and therapeutic decision making for LNM. Additionally, this general computational approach may prove useful in other contexts.
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Pathologist Validation of a Machine Learning–Derived Feature for Colon Cancer Risk Stratification
Vincenzo L’Imperio
Markus Plass
Heimo Müller
Nicolò Tamini
Luca Gianotti
Nicola Zucchini
Robert Reihs
Lily Peng
Cameron Chen
Marialuisa Lavitrano
David F. Steiner
Kurt Zatloukal
Fabio Pagni
JAMA Network Open(2023)
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Importance: Identifying new prognostic features in colon cancer has the potential to refine histopathologic review and inform patient care. Although prognostic artificial intelligence systems have recently demonstrated significant risk stratification for several cancer types, studies have not yet shown that the machine learning–derived features associated with these prognostic artificial intelligence systems are both interpretable and usable by pathologists.
Objective: To evaluate whether pathologist scoring of a histopathologic feature previously identified by machine learning is associated with survival among patients with colon cancer.
Design, Setting, and Participants: This prognostic study used deidentified, archived colorectal cancer cases from January 2013 to December 2015 from the University of Milano-Bicocca. All available histologic slides from 258 consecutive colon adenocarcinoma cases were reviewed from December 2021 to February 2022 by 2 pathologists, who conducted semiquantitative scoring for tumor adipose feature (TAF), which was previously identified via a prognostic deep learning model developed with an independent colorectal cancer cohort.
Main Outcomes and Measures: Prognostic value of TAF for overall survival and disease-specific survival as measured by univariable and multivariable regression analyses. Interpathologist agreement in TAF scoring was also evaluated.
Results: A total of 258 colon adenocarcinoma histopathologic cases from 258 patients (138 men [53%]; median age, 67 years [IQR, 65-81 years]) with stage II (n = 119) or stage III (n = 139) cancer were included. Tumor adipose feature was identified in 120 cases (widespread in 63 cases, multifocal in 31, and unifocal in 26). For overall survival analysis after adjustment for tumor stage, TAF was independently prognostic in 2 ways: TAF as a binary feature (presence vs absence: hazard ratio [HR] for presence of TAF, 1.55 [95% CI, 1.07-2.25]; P = .02) and TAF as a semiquantitative categorical feature (HR for widespread TAF, 1.87 [95% CI, 1.23-2.85]; P = .004). Interpathologist agreement for widespread TAF vs lower categories (absent, unifocal, or multifocal) was 90%, corresponding to a κ metric at this threshold of 0.69 (95% CI, 0.58-0.80).
Conclusions and Relevance: In this prognostic study, pathologists were able to learn and reproducibly score for TAF, providing significant risk stratification on this independent data set. Although additional work is warranted to understand the biological significance of this feature and to establish broadly reproducible TAF scoring, this work represents the first validation to date of human expert learning from machine learning in pathology. Specifically, this validation demonstrates that a computationally identified histologic feature can represent a human-identifiable, prognostic feature with the potential for integration into pathology practice.
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