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Rory Sayres

Rory Sayres

Rory is a researcher in the Google Health AI group. He focuses on intelligence augmentation of medical experts using machine-learning-based assistance. His background includes neuroscience and human/computer interaction. He has previously studied the human visual system using methods including psychophysics and functional magnetic resonance imaging.
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    Differences between Patient and Clinician Submitted Images: Implications for Virtual Care of Skin Conditions
    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)
    Preview abstract 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. View details
    Validation of a deep learning system for the detection of diabetic retinopathy in Indigenous Australians
    Mark Chia
    Fred Hersch
    Pearse Keane
    Angus Turner
    British Journal of Ophthalmology, vol. 108 (2024), pp. 268-273
    Preview abstract Background/aims: Deep learning systems (DLSs) for diabetic retinopathy (DR) detection show promising results but can underperform in racial and ethnic minority groups, therefore external validation within these populations is critical for health equity. This study evaluates the performance of a DLS for DR detection among Indigenous Australians, an understudied ethnic group who suffer disproportionately from DR-related blindness. Methods: We performed a retrospective external validation study comparing the performance of a DLS against a retinal specialist for the detection of more-than-mild DR (mtmDR), vision-threatening DR (vtDR) and all-cause referable DR. The validation set consisted of 1682 consecutive, single-field, macula-centred retinal photographs from 864 patients with diabetes (mean age 54.9 years, 52.4% women) at an Indigenous primary care service in Perth, Australia. Three-person adjudication by a panel of specialists served as the reference standard. Results: For mtmDR detection, sensitivity of the DLS was superior to the retina specialist (98.0% (95% CI, 96.5 to 99.4) vs 87.1% (95% CI, 83.6 to 90.6), McNemar’s test p<0.001) with a small reduction in specificity (95.1% (95% CI, 93.6 to 96.4) vs 97.0% (95% CI, 95.9 to 98.0), p=0.006). For vtDR, the DLS’s sensitivity was again superior to the human grader (96.2% (95% CI, 93.4 to 98.6) vs 84.4% (95% CI, 79.7 to 89.2), p<0.001) with a slight drop in specificity (95.8% (95% CI, 94.6 to 96.9) vs 97.8% (95% CI, 96.9 to 98.6), p=0.002). For all-cause referable DR, there was a substantial increase in sensitivity (93.7% (95% CI, 91.8 to 95.5) vs 74.4% (95% CI, 71.1 to 77.5), p<0.001) and a smaller reduction in specificity (91.7% (95% CI, 90.0 to 93.3) vs 96.3% (95% CI, 95.2 to 97.4), p<0.001). Conclusion: The DLS showed improved sensitivity and similar specificity compared with a retina specialist for DR detection. This demonstrates its potential to support DR screening among Indigenous Australians, an underserved population with a high burden of diabetic eye disease. View details
    Real-time diabetic retinopathy screening by deep learning in a multisite national screening programme: a prospective interventional cohort study
    Dr. Paisan Raumviboonsuk
    Variya Nganthavee
    Kornwipa Hemarat
    Apinpat Kongprayoon
    Rajiv Raman
    Brian Levinstein
    Roy Lee
    Sunny Virmani
    John Chambers
    Fred Hersch
    Lily Hao Yi Peng
    The Lancet Digital Health (2022)
    Preview abstract Background: Diabetic retinopathy is a leading cause of preventable blindness, especially in low-income and middle-income countries (LMICs). Deep-learning systems have the potential to enhance diabetic retinopathy screenings in these settings, yet prospective studies assessing their usability and performance are scarce. Methods: We did a prospective interventional cohort study to evaluate the real-world performance and feasibility of deploying a deep-learning system into the health-care system of Thailand. Patients with diabetes and listed on the national diabetes registry, aged 18 years or older, able to have their fundus photograph taken for at least one eye, and due for screening as per the Thai Ministry of Public Health guidelines were eligible for inclusion. Eligible patients were screened with the deep-learning system at nine primary care sites under Thailand's national diabetic retinopathy screening programme. Patients with a previous diagnosis of diabetic macular oedema, severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy; previous laser treatment of the retina or retinal surgery; other non-diabetic retinopathy eye disease requiring referral to an ophthalmologist; or inability to have fundus photograph taken of both eyes for any reason were excluded. Deep-learning system-based interpretations of patient fundus images and referral recommendations were provided in real time. As a safety mechanism, regional retina specialists over-read each image. Performance of the deep-learning system (accuracy, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) were measured against an adjudicated reference standard, provided by fellowship-trained retina specialists. This study is registered with the Thai national clinical trials registry, TCRT20190902002. Findings: Between Dec 12, 2018, and March 29, 2020, 7940 patients were screened for inclusion. 7651 (96·3%) patients were eligible for study analysis, and 2412 (31·5%) patients were referred for diabetic retinopathy, diabetic macular oedema, ungradable images, or low visual acuity. For vision-threatening diabetic retinopathy, the deep-learning system had an accuracy of 94·7% (95% CI 93·0–96·2), sensitivity of 91·4% (87·1–95·0), and specificity of 95·4% (94·1–96·7). The retina specialist over-readers had an accuracy of 93·5 (91·7–95·0; p=0·17), a sensitivity of 84·8% (79·4–90·0; p=0·024), and specificity of 95·5% (94·1–96·7; p=0·98). The PPV for the deep-learning system was 79·2 (95% CI 73·8–84·3) compared with 75·6 (69·8–81·1) for the over-readers. The NPV for the deep-learning system was 95·5 (92·8–97·9) compared with 92·4 (89·3–95·5) for the over-readers. Interpretation: A deep-learning system can deliver real-time diabetic retinopathy detection capability similar to retina specialists in community-based screening settings. Socioenvironmental factors and workflows must be taken into consideration when implementing a deep-learning system within a large-scale screening programme in LMICs. Funding: Google and Rajavithi Hospital, Bangkok, Thailand. View details
    Preview abstract Background: Many dermatologic cases are first evaluated by primary care physicians or nurse practitioners. Objective: This study aimed to evaluate an artificial intelligence (AI)-based tool that assists with interpreting dermatologic conditions. Methods: We developed an AI-based tool and conducted a randomized multi-reader, multi-case study (20 primary care physicians, 20 nurse practitioners, and 1047 retrospective teledermatology cases) to evaluate its utility. Cases were enriched and comprised 120 skin conditions. Readers were recruited to optimize for geographical diversity; the primary care physicians practiced across 12 states (2-32 years of experience, mean 11.3 years), and the nurse practitioners practiced across 9 states (2-34 years of experience, mean 13.1 years). To avoid memory effects from incomplete washout, each case was read once by each clinician either with or without AI assistance, with the assignment randomized. The primary analyses evaluated the top-1 agreement, defined as the agreement rate of the clinicians’ primary diagnosis with the reference diagnoses provided by a panel of dermatologists (per case: 3 dermatologists from a pool of 12, practicing across 8 states, with 5-13 years of experience, mean 7.2 years of experience). We additionally conducted subgroup analyses stratified by cases’ self-reported race and ethnicity and measured the performance spread: the maximum performance subtracted by the minimum across subgroups. Results: The AI’s standalone top-1 agreement was 63%, and AI assistance was significantly associated with higher agreement with reference diagnoses. For primary care physicians, the increase in diagnostic agreement was 10% (P<.001), from 48% to 58%; for nurse practitioners, the increase was 12% (P<.001), from 46% to 58%. When stratified by cases’ self-reported race or ethnicity, the AI’s performance was 59%-62% for Asian, Native Hawaiian, Pacific Islander, other, and Hispanic or Latinx individuals and 67% for both Black or African American and White subgroups. For the clinicians, AI assistance–associated improvements across subgroups were in the range of 8%-12% for primary care physicians and 8%-15% for nurse practitioners. The performance spread across subgroups was 5.3% unassisted vs 6.6% assisted for primary care physicians and 5.2% unassisted vs 6.0% assisted for nurse practitioners. In both unassisted and AI-assisted modalities, and for both primary care physicians and nurse practitioners, the subgroup with the highest performance on average was Black or African American individuals, though the differences with other subgroups were small and had overlapping 95% CIs. Conclusions: AI assistance was associated with significantly improved diagnostic agreement with dermatologists. Across race and ethnicity subgroups, for both primary care physicians and nurse practitioners, the effect of AI assistance remained high at 8%-15%, and the performance spread was similar at 5%-7%. View details
    Preview abstract Importance: Most dermatologic cases are initially evaluated by nondermatologists such as primary care physicians (PCPs) or nurse practitioners (NPs). Objective: To evaluate an artificial intelligence (AI)–based tool that assists with diagnoses of dermatologic conditions. Design, Setting, and Participants: This multiple-reader, multiple-case diagnostic study developed an AI-based tool and evaluated its utility. Primary care physicians and NPs retrospectively reviewed an enriched set of cases representing 120 different skin conditions. Randomization was used to ensure each clinician reviewed each case either with or without AI assistance; each clinician alternated between batches of 50 cases in each modality. The reviews occurred from February 21 to April 28, 2020. Data were analyzed from May 26, 2020, to January 27, 2021. Exposures: An AI-based assistive tool for interpreting clinical images and associated medical history. Main Outcomes and Measures: The primary analysis evaluated agreement with reference diagnoses provided by a panel of 3 dermatologists for PCPs and NPs. Secondary analyses included diagnostic accuracy for biopsy-confirmed cases, biopsy and referral rates, review time, and diagnostic confidence. Results: Forty board-certified clinicians, including 20 PCPs (14 women [70.0%]; mean experience, 11.3 [range, 2-32] years) and 20 NPs (18 women [90.0%]; mean experience, 13.1 [range, 2-34] years) reviewed 1048 retrospective cases (672 female [64.2%]; median age, 43 [interquartile range, 30-56] years; 41 920 total reviews) from a teledermatology practice serving 11 sites and provided 0 to 5 differential diagnoses per case (mean [SD], 1.6 [0.7]). The PCPs were located across 12 states, and the NPs practiced in primary care without physician supervision across 9 states. The NPs had a mean of 13.1 (range, 2-34) years of experience and practiced in primary care without physician supervision across 9 states. Artificial intelligence assistance was significantly associated with higher agreement with reference diagnoses. For PCPs, the increase in diagnostic agreement was 10% (95% CI, 8%-11%; P < .001), from 48% to 58%; for NPs, the increase was 12% (95% CI, 10%-14%; P < .001), from 46% to 58%. In secondary analyses, agreement with biopsy-obtained diagnosis categories of maglignant, precancerous, or benign increased by 3% (95% CI, −1% to 7%) for PCPs and by 8% (95% CI, 3%-13%) for NPs. Rates of desire for biopsies decreased by 1% (95% CI, 0-3%) for PCPs and 2% (95% CI, 1%-3%) for NPs; the rate of desire for referrals decreased by 3% (95% CI, 1%-4%) for PCPs and NPs. Diagnostic agreement on cases not indicated for a dermatologist referral increased by 10% (95% CI, 8%-12%) for PCPs and 12% (95% CI, 10%-14%) for NPs, and median review time increased slightly by 5 (95% CI, 0-8) seconds for PCPs and 7 (95% CI, 5-10) seconds for NPs per case. Conclusions and Relevance: Artificial intelligence assistance was associated with improved diagnoses by PCPs and NPs for 1 in every 8 to 10 cases, indicating potential for improving the quality of dermatologic care. View details
    Iterative quality control strategies for expert medical image labeling
    Sonia Phene
    Abigail Huang
    Rebecca Ackermann
    Olga Kanzheleva
    Proceedings of the AAAI Conference on Human Computation and Crowdsourcing (2021)
    Preview abstract Data quality is a key concern for artificial intelligence (AI) efforts that rely upon crowdsourced data collection. In the domain of medicine in particular, labeled data must meet higher quality standards, or the resulting AI may lead to patient harm, and/or perpetuate biases. What are the challenges involved in expert medical labeling? What processes do such teams employ? In this study, we interviewed members of teams developing AI for medical imaging across 4 subdomains (ophthalmology, radiology, pathology, and dermatology). We identify a set of common practices for ensuring data quality. We describe one instance of low-quality labeling caught by post-launch monitoring. However, the more common pattern is to involve experts in an iterative process of defining, testing, and iterating tasks and instructions. Teams invest in these upstream efforts in order to mitigate downstream quality issues during large-scale labeling. View details
    Evaluation of the Use of Combined Artificial Intelligence and Pathologist Assessment to Review and Grade Prostate Biopsies
    Kunal Nagpal
    Davis J. Foote
    Adam Pearce
    Samantha Winter
    Matthew Symonds
    Liron Yatziv
    Trissia Brown
    Isabelle Flament-Auvigne
    Fraser Tan
    Martin C. Stumpe
    Cameron Chen
    Craig Mermel
    JAMA Network Open (2020)
    Preview abstract Importance: Expert-level artificial intelligence (AI) algorithms for prostate biopsy grading have recently been developed. However, the potential impact of integrating such algorithms into pathologist workflows remains largely unexplored. Objective: To evaluate an expert-level AI-based assistive tool when used by pathologists for the grading of prostate biopsies. Design, Setting, and Participants: This diagnostic study used a fully crossed multiple-reader, multiple-case design to evaluate an AI-based assistive tool for prostate biopsy grading. Retrospective grading of prostate core needle biopsies from 2 independent medical laboratories in the US was performed between October 2019 and January 2020. A total of 20 general pathologists reviewed 240 prostate core needle biopsies from 240 patients. Each pathologist was randomized to 1 of 2 study cohorts. The 2 cohorts reviewed every case in the opposite modality (with AI assistance vs without AI assistance) to each other, with the modality switching after every 10 cases. After a minimum 4-week washout period for each batch, the pathologists reviewed the cases for a second time using the opposite modality. The pathologist-provided grade group for each biopsy was compared with the majority opinion of urologic pathology subspecialists. Exposure: An AI-based assistive tool for Gleason grading of prostate biopsies. Main Outcomes and Measures: Agreement between pathologists and subspecialists with and without the use of an AI-based assistive tool for the grading of all prostate biopsies and Gleason grade group 1 biopsies. Results: Biopsies from 240 patients (median age, 67 years; range, 39-91 years) with a median prostate-specific antigen level of 6.5 ng/mL (range, 0.6-97.0 ng/mL) were included in the analyses. Artificial intelligence–assisted review by pathologists was associated with a 5.6% increase (95% CI, 3.2%-7.9%; P < .001) in agreement with subspecialists (from 69.7% for unassisted reviews to 75.3% for assisted reviews) across all biopsies and a 6.2% increase (95% CI, 2.7%-9.8%; P = .001) in agreement with subspecialists (from 72.3% for unassisted reviews to 78.5% for assisted reviews) for grade group 1 biopsies. A secondary analysis indicated that AI assistance was also associated with improvements in tumor detection, mean review time, mean self-reported confidence, and interpathologist agreement. Conclusions and Relevance: In this study, the use of an AI-based assistive tool for the review of prostate biopsies was associated with improvements in the quality, efficiency, and consistency of cancer detection and grading. View details
    Expert Discussions Improve Comprehension of Difficult Cases in Medical Image Assessment
    Abigail E. Huang
    ACM CHI Conference on Human Factors in Computing Systems (CHI 2020) (2020) (to appear)
    Preview abstract Medical data labeling workflows critically depend on accurate assessments from human experts. Yet human assessments can vary markedly, even among medical experts. Prior research has demonstrated benefits of labeler training on performance. Here we utilized two types of labeler training feedback: highlighting incorrect labels for difficult cases ("individual performance" feedback), and expert discussions from adjudication of these cases. We presented ten non-specialist eye care professionals with either individual performance alone, or individual performance and expert discussions. Compared to performance feedback alone, seeing expert discussions significantly improved non-specialists' understanding of the rationale behind the correct diagnosis while motivating changes in their own labeling approach; and also significantly improved average accuracy on one of four pathologies in a held-out test set. This work suggests that image adjudication may provide benefits beyond developing trusted consensus labels, and that exposure to specialist discussions can be an effective training intervention for medical diagnosis. View details
    Preview abstract ML models often exhibit unexpectedly poor behavior when they are deployed in real-world domains. We identify underspecification as a key reason for these failures. An ML pipeline is underspecified when it can return many predictors with equivalently strong held-out performance in the training domain. Underspecification is common in modern ML pipelines, such as those based on deep learning. Predictors returned by underspecified pipelines are often treated as equivalent based on their training domain performance, but we show here that such predictors can behave very differently in deployment domains. This ambiguity can lead to instability and poor model behavior in practice, and is a distinct failure mode from previously identified issues arising from structural mismatch between training and deployment domains. We show that this problem appears in a wide variety of practical ML pipelines, using examples from computer vision, medical imaging, natural language processing, clinical risk prediction based on electronic health records, and medical genomics. Our results show the need to explicitly account for underspecification in modeling pipelines that are intended for real-world deployment in any domain. View details
    Longitudinal Screening for Diabetic Retinopathy in a Nationwide Screening Program: Comparing Deep Learning and Human Graders
    Jirawut Limwattanayingyong
    Variya Nganthavee
    Kasem Seresirikachorn
    Tassapol Singalavanija
    Ngamphol Soonthornworasiri
    Varis Ruamviboonsuk
    Chetan Rao
    Rajiv Raman
    Andrzej Grzybowski
    Lily Hao Yi Peng
    Fred Hersch
    Richa Tiwari, PhD
    Dr. Paisan Raumviboonsuk
    Journal of Diabetes Research (2020)
    Preview abstract Objective. To evaluate diabetic retinopathy (DR) screening via deep learning (DL) and trained human graders (HG) in a longitudinal cohort, as case spectrum shifts based on treatment referral and new-onset DR. Methods. We randomly selected patients with diabetes screened twice, two years apart within a nationwide screening program. The reference standard was established via adjudication by retina specialists. Each patient’s color fundus photographs were graded, and a patient was considered as having sight-threatening DR (STDR) if the worse eye had severe nonproliferative DR, proliferative DR, or diabetic macular edema. We compared DR screening via two modalities: DL and HG. For each modality, we simulated treatment referral by excluding patients with detected STDR from the second screening using that modality. Results. There were 5,738 patients (12.3% STDR) in the first screening. DL and HG captured different numbers of STDR cases, and after simulated referral and excluding ungradable cases, 4,148 and 4,263 patients remained in the second screening, respectively. The STDR prevalence at the second screening was 5.1% and 6.8% for DL- and HG-based screening, respectively. Along with the prevalence decrease, the sensitivity for both modalities decreased from the first to the second screening (DL: from 95% to 90%, p=0.008; HG: from 74% to 57%, p<0.001). At both the first and second screenings, the rate of false negatives for the DL was a fifth that of HG (0.5-0.6% vs. 2.9-3.2%). Conclusion. On 2-year longitudinal follow-up of a DR screening cohort, STDR prevalence decreased for both DL- and HG-based screening. Follow-up screenings in longitudinal DR screening can be more difficult and induce lower sensitivity for both DL and HG, though the false negative rate was substantially lower for DL. Our data may be useful for health-economics analyses of longitudinal screening settings. View details
    Preview abstract Artificial intelligence (AI) methods have become a focus of intense interest within the eye care community. This parallels a wider interest in AI as it has started impacting many facets of society. However, understanding across the community has not kept pace with technical developments. What is AI? How does it relate to other terms like machine learning (ML) or deep learning (DL)? How is AI currently used within eye care, and how might it be used in the future? This review paper provides an overview of these concepts for eye care specialists. We explain core concepts in AI, describe how these methods have been applied in ophthalmology, and consider future directions and challenges. We walk through the steps needed to develop an AI system for eye disease, and discuss the challenges in validating and deploying such technology. We argue that among medical fields, ophthalmology may be uniquely positioned to benefit from the thoughtful deployment of AI to improve patient care. View details
    Deep learning versus human graders for classifying diabetic retinopathy severity in a nationwide screening program
    Dr. Paisan Raumviboonsuk
    Dr. Peranut Chotcomwongse
    Rajiv Raman
    Sonia Phene
    Kornwipa Hemarat
    Mongkol Tadarati
    Sukhum Silpa-Archa
    Jirawut Limwattanayingyong
    Chetan Rao
    Oscar Kuruvilla
    Jesse Jung
    Jeffrey Tan
    Surapong Orprayoon
    Chawawat Kangwanwongpaisan
    Ramase Sukumalpaiboon
    Chainarong Luengchaichawang
    Jitumporn Fuangkaew
    Pipat Kongsap
    Lamyong Chualinpha
    Sarawuth Saree
    Srirut Kawinpanitan
    Korntip Mitvongsa
    Siriporn Lawanasakol
    Chaiyasit Thepchatri
    Lalita Wongpichedchai
    Lily Peng
    Nature Partner Journal (npj) Digital Medicine (2019)
    Preview abstract Deep learning algorithms have been used to detect diabetic retinopathy (DR) with specialist-level accuracy. This study aims to validate one such algorithm on a large-scale clinical population, and compare the algorithm performance with that of human graders. A total of 25,326 gradable retinal images of patients with diabetes from the community-based, nationwide screening program of DR in Thailand were analyzed for DR severity and referable diabetic macular edema (DME). Grades adjudicated by a panel of international retinal specialists served as the reference standard. Relative to human graders, for detecting referable DR (moderate NPDR or worse), the deep learning algorithm had significantly higher sensitivity (0.97 vs. 0.74, p < 0.001), and a slightly lower specificity (0.96 vs. 0.98, p < 0.001). Higher sensitivity of the algorithm was also observed for each of the categories of severe or worse NPDR, PDR, and DME (p < 0.001 for all comparisons). The quadratic-weighted kappa for determination of DR severity levels by the algorithm and human graders was 0.85 and 0.78 respectively (p < 0.001 for the difference). Across different severity levels of DR for determining referable disease, deep learning significantly reduced the false negative rate (by 23%) at the cost of slightly higher false positive rates (2%). Deep learning algorithms may serve as a valuable tool for DR screening. View details
    Preview abstract Purpose: To present and evaluate a remote, tool-based system and structured grading rubric for adjudicating image-based diabetic retinopathy (DR) grades. Methods: We compared three different procedures for adjudicating DR severity assessments among retina specialist panels, including (1) in-person adjudication based on a previously described procedure (Baseline), (2) remote, tool-based adjudication for assessing DR severity alone (TA), and (3) remote, tool-based adjudication using a feature-based rubric (TA-F). We developed a system allowing graders to review images remotely and asynchronously. For both TA and TA-F approaches, images with disagreement were reviewed by all graders in a round-robin fashion until disagreements were resolved. Five panels of three retina specialists each adjudicated a set of 499 retinal fundus images (1 panel using Baseline, 2 using TA, and 2 using TA-F adjudication). Reliability was measured as grade agreement among the panels using Cohen's quadratically weighted kappa. Efficiency was measured as the number of rounds needed to reach a consensus for tool-based adjudication. Results: The grades from remote, tool-based adjudication showed high agreement with the Baseline procedure, with Cohen's kappa scores of 0.948 and 0.943 for the two TA panels, and 0.921 and 0.963 for the two TA-F panels. Cases adjudicated using TA-F were resolved in fewer rounds compared with TA (P < 0.001; standard permutation test). Conclusions: Remote, tool-based adjudication presents a flexible and reliable alternative to in-person adjudication for DR diagnosis. Feature-based rubrics can help accelerate consensus for tool-based adjudication of DR without compromising label quality. Translational Relevance: This approach can generate reference standards to validate automated methods, and resolve ambiguous diagnoses by integrating into existing telemedical workflows. View details
    Preview abstract Purpose To develop and validate a deep learning (DL) algorithm that predicts referable glaucomatous optic neuropathy (GON) and optic nerve head (ONH) features from color fundus images, to determine the relative importance of these features in referral decisions by glaucoma specialists (GSs) and the algorithm, and to compare the performance of the algorithm with eye care providers. Design Development and validation of an algorithm. Participants Fundus images from screening programs, studies, and a glaucoma clinic. Methods A DL algorithm was trained using a retrospective dataset of 86 618 images, assessed for glaucomatous ONH features and referable GON (defined as ONH appearance worrisome enough to justify referral for comprehensive examination) by 43 graders. The algorithm was validated using 3 datasets: dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of GSs; dataset B (9642 images, 1 image/patient; 9.2% referable), images from a diabetic teleretinal screening program; and dataset C (346 images, 1 image/patient; 81.7% referable), images from a glaucoma clinic. Main Outcome Measures The algorithm was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for referable GON and glaucomatous ONH features. Results The algorithm’s AUC for referable GON was 0.945 (95% confidence interval [CI], 0.929–0.960) in dataset A, 0.855 (95% CI, 0.841–0.870) in dataset B, and 0.881 (95% CI, 0.838–0.918) in dataset C. Algorithm AUCs ranged between 0.661 and 0.973 for glaucomatous ONH features. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders (including 1 GS), while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels. Conclusions A DL algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup. View details
    Using a deep learning algorithm and integrated gradient explanation to assist grading for diabetic retinopathy
    Ankur Taly
    Anthony Joseph
    Arjun Sood
    Arun Narayanaswamy
    Derek Wu
    Ehsan Rahimy
    Jesse Smith
    Katy Blumer
    Lily Peng
    Michael Shumski
    Scott Barb
    Zahra Rastegar
    Ophthalmology (2019)
    Preview abstract Background Deep learning methods have recently produced algorithms that can detect disease such as diabetic retinopathy (DR) with doctor-level accuracy. We sought to understand the impact of these models on physician graders in assisted-read settings. Methods We surfaced model predictions and explanation maps ("masks") to 9 ophthalmologists with varying levels of experience to read 1,804 images each for DR severity based on the International Clinical Diabetic Retinopathy (ICDR) disease severity scale. The image sample was representative of the diabetic screening population, and was adjudicated by 3 retina specialists for a reference standard. Doctors read each image in one of 3 conditions: Unassisted, Grades Only, or Grades+Masks. Findings Readers graded DR more accurately with model assistance than without (p < 0.001, logistic regression). Compared to the adjudicated reference standard, for cases with disease, 5-class accuracy was 57.5% for the model. For graders, 5-class accuracy for cases with disease was 47.5 ± 5.6% unassisted, 56.9 ± 5.5% with Grades Only, and 61.5 ± 5.5% with Grades+Mask. Reader performance improved with assistance across all levels of DR, including for severe and proliferative DR. Model assistance increased the accuracy of retina fellows and trainees above that of the unassisted grader or model alone. Doctors’ grading confidence scores and read times both increased overall with assistance. For most cases, Grades + Masks was as only effective as Grades Only, though masks provided additional benefit over grades alone in cases with: some DR and low model certainty; low image quality; and proliferative diabetic retinopathy (PDR) with features that were frequently missed, such as panretinal photocoagulation (PRP) scars. Interpretation Taken together, these results show that deep learning models can improve the accuracy of, and confidence in, DR diagnosis in an assisted read setting. View details
    Direct Uncertainty Prediction for Medical Second Opinions
    Maithra Raghu
    Katy Blumer
    Ziad Obermeyer
    Robert Kleinberg
    Sendhil Mullainathan
    Jon Kleinberg
    ICML (2019)
    Preview abstract The issue of disagreements amongst human experts is a ubiquitous one in both machine learning and medicine. In medicine, this often corresponds to doctor disagreements on a patient diagnosis. In this work, we show that machine learning models can be successfully trained to give uncertainty scores to data instances that result in high expert disagreements. In particular, they can identify patient cases that would benefit most from a medical second opinion. Our central methodological finding is that Direct Uncertainty Prediction (DUP), training a model to predict an uncertainty score directly from the raw patient features, works better than Uncertainty Via Classification, the two step process of training a classifier and postprocessing the output distribution to give an uncertainty score. We show this both with a theoretical result, and on extensive evaluations on a large scale medical imaging application. View details
    Preview abstract The interpretation of deep learning models is a challenge due to their size, complexity, and often opaque internal state. In addition, many systems, such as image classifiers, operate on low-level features rather than high-level concepts. To address these challenges, we introduce Concept Activation Vectors (CAVs), which provide an interpretation of a neural net's internal state in terms of human-friendly concepts. The key idea is to view the high-dimensional internal state of a neural net as an aid, not an obstacle. We show how to use CAVs as part of a technique, Testing with CAVs (TCAV), that uses directional derivatives to quantify the degree to which a user-defined concept is important to a classification result--for example, how sensitive a prediction of “zebra” is to the presence of stripes. Using the domain of image classification as a testing ground, we describe how CAVs may be used to explore hypotheses and generate insights for a standard image classification network as well as a medical application. View details
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