Quoc V. Le, Marc'Aurelio Ranzato, Rajat Monga, Matthieu Devin, Kai Chen, Greg S. Corrado, Jeff Dean, Andrew Y. Ng
We consider the problem of building high-level, class-specific feature detectors from only unlabeled data. For example, is it possible to learn a face detector using only unlabeled images? To answer this, we train a 9-layered locally connected sparse autoencoder with pooling and local contrast normalization on a large dataset of images (the model has 1 billion connections, the dataset has 10 million 200x200 pixel images downloaded from the Internet). We train this network using model parallelism and asynchronous SGD on a cluster with 1,000 machines (16,000 cores) for three days. Contrary to what appears to be a widely-held intuition, our experimental results reveal that it is possible to train a face detector without having to label images as containing a face or not. Control experiments show that this feature detector is robust not only to translation but also to scaling and out-of-plane rotation. We also find that the same network is sensitive to other high-level concepts such as cat faces and human bodies. Starting with these learned features, we trained our network to obtain 15.8% accuracy in recognizing 20,000 object categories from ImageNet, a leap of 70% relative improvement over the previous state-of-the-art.
Boris Babenko, Siva Balasubramanian, Katy E. Blumer, Greg S. Corrado, Lily Peng, Dale R. Webster, Naama Hammel, Avinash V. Varadarajan
Background: Patients with neovascular age-related macular degeneration (AMD) can avoid vision loss via certain therapy. However, methods to predict the progression to neovascular age-related macular degeneration (nvAMD) are lacking. Purpose: To develop and validate a deep learning (DL) algorithm to predict 1-year progression of eyes with no, early, or intermediate AMD to nvAMD, using color fundus photographs (CFP). Design: Development and validation of a DL algorithm. Methods: We trained a DL algorithm to predict 1-year progression to nvAMD, and used 10-fold cross-validation to evaluate this approach on two groups of eyes in the Age-Related Eye Disease Study (AREDS): none/early/intermediate AMD, and intermediate AMD (iAMD) only. We compared the DL algorithm to the manually graded 4-category and 9-step scales in the AREDS dataset. Main outcome measures: Performance of the DL algorithm was evaluated using the sensitivity at 80% specificity for progression to nvAMD. Results: The DL algorithm's sensitivity for predicting progression to nvAMD from none/early/iAMD (78+/-6%) was higher than manual grades from the 9-step scale (67+/-8%) or the 4-category scale (48+/-3%). For predicting progression specifically from iAMD, the DL algorithm's sensitivity (57+/-6%) was also higher compared to the 9-step grades (36+/-8%) and the 4-category grades (20+/-0%). Conclusions: Our DL algorithm performed better in predicting progression to nvAMD than manual grades. Future investigations are required to test the application of this DL algorithm in a real-world clinical setting.
Paisan Raumviboonsuk, Jonathan Krause, Peranut Chotcomwongse, Rory Sayres, Rajiv Raman, Kasumi Widner, Bilson J L Campana, Sonia Phene, Kornwipa Hemarat, Mongkol Tadarati, Sukhum Silpa-Acha, Jirawut Limwattanayingyong, Chetan Rao, Oscar Kuruvilla, Jesse Jung, Jeffrey Tan, Surapong Orprayoon, Chawawat Kangwanwongpaisan, Ramase Sukulmalpaiboon, Chainarong Luengchaichawang, Jitumporn Fuangkaew, Pipat Kongsap, Lamyong Chualinpha, Sarawuth Saree, Srirat Kawinpanitan, Korntip Mitvongsa, Siriporn Lawanasakol, Chaiyasit Thepchatri, Lalita Wongpichedchai, Greg S Corrado, Lily Peng, Dale R Webster
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. 25,326 gradable retinal images of patients with diabetes from the community-based, nation-wide 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. 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.
Yuan Liu, Ayush Jain, Clara Eng, David H. Way, Kang Lee, Peggy Bui, Kimberly Kanada, Guilherme de Oliveira Marinho, Jessica Gallegos, Sara Gabriele, Vishakha Gupta, Nalini Singh, Vivek Natarajan, Rainer Hofmann-Wellenhof, Greg S. Corrado, Lily H. Peng, Dale R. Webster, Dennis Ai, Susan Huang, Yun Liu, R. Carter Dunn, David Coz
Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.
Ellery Wulczyn, David F. Steiner, Melissa Moran, Markus Plass, Robert Reihs, Fraser Tan, Isabelle Flament-Auvigne, Trissia Brown, Peter Regitnig, Po-Hsuan Cameron Chen, Narayan Hegde, Apaar Sadhwani, Robert MacDonald, Benny Ayalew, Greg S. Corrado, Lily H. Peng, Daniel Tse, Heimo Müller, Zhaoyang Xu, Yun Liu, Martin C. Stumpe, Kurt Zatloukal, Craig H. Mermel
Deriving interpretable prognostic features from deep-learning-based prognostic histopathology models remains a challenge. In this study, we developed a deep learning system (DLS) for predicting disease specific survival for stage II and III colorectal cancer using 3,652 cases (27,300 slides). When evaluated on two validation datasets containing 1,239 cases (9,340 slides) and 738 cases (7,140 slides) respectively, the DLS achieved a 5-year disease-specific survival AUC of 0.70 (95%CI 0.66-0.73) and 0.69 (95%CI 0.64-0.72), and added significant predictive value to a set of 9 clinicopathologic features. To interpret the DLS, we explored the ability of different human-interpretable features to explain the variance in DLS scores. We observed that clinicopathologic features such as T-category, N-category, and grade explained a small fraction of the variance in DLS scores (R2=18% in both validation sets). Next, we generated human-interpretable histologic features by clustering embeddings from a deep-learning based image-similarity model and showed that they explain the majority of the variance (R2 of 73% to 80%). Furthermore, the clustering-derived feature most strongly associated with high DLS scores was also highly prognostic in isolation. With a distinct visual appearance (poorly differentiated tumor cell clusters adjacent to adipose tissue), this feature was identified by annotators with 87.0-95.5% accuracy. Our approach can be used to explain predictions from a prognostic deep learning model and uncover potentially-novel prognostic features that can be reliably identified by people for future validation studies.
Oran Lang, Doron Yaya-Stupp, Ilana Traynis, Heather Cole-Lewis, Chloe R. Bennett, Courtney Lyles, Charles Lau, Michal Irani, Christopher Semturs, Dale R. Webster, Greg S. Corrado, Avinatan Hassidim, Yossi Matias, Yun Liu, Naama Hammel, Boris Babenko
AI models have shown promise in many medical imaging tasks. However, our ability to explain what signals these models have learned is severely lacking. Explanations are needed in order to increase the trust in AI-based models, and could enable novel scientific discovery by uncovering signals in the data that are not yet known to experts. In this paper, we present a method for automatic visual explanations leveraging team-based expertise by generating hypotheses of what visual signals in the images are correlated with the task. We propose the following 4 steps: (i) Train a classifier to perform a given task (ii) Train a classifier guided StyleGAN-based image generator (StylEx) (iii) Automatically detect and visualize the top visual attributes that the classifier is sensitive towards (iv) Formulate hypotheses for the underlying mechanisms, to stimulate future research. Specifically, we present the discovered attributes to an interdisciplinary panel of experts so that hypotheses can account for social and structural determinants of health. We demonstrate results on eight prediction tasks across three medical imaging modalities: retinal fundus photographs, external eye photographs, and chest radiographs. We showcase examples of attributes that capture clinically known features, confounders that arise from factors beyond physiological mechanisms, and reveal a number of physiologically plausible novel attributes. Our approach has the potential to enable researchers to better understand, improve their assessment, and extract new knowledge from AI-based models. Importantly, we highlight that attributes generated by our framework can capture phenomena beyond physiology or pathophysiology, reflecting the real world nature of healthcare delivery and socio-cultural factors. Finally, we intend to release code to enable researchers to train their own StylEx models and analyze their predictive tasks.
Narayan Hegde, Jason D. Hipp, Yun Liu, Michael E. Buck, Emily Reif, Daniel Smilkov, Michael Terry, Carrie J. Cai, Mahul B. Amin, Craig H. Mermel, Phil Q. Nelson, Lily H. Peng, Greg S. Corrado, Martin C. Stumpe
The increasing availability of large institutional and public histopathology image datasets is enabling the searching of these datasets for diagnosis, research, and education. Though these datasets typically have associated metadata such as diagnosis or clinical notes, even carefully curated datasets rarely contain annotations of the location of regions of interest on each image. Because pathology images are extremely large (up to 100,000 pixels in each dimension), further laborious visual search of each image may be needed to find the feature of interest. In this paper, we introduce a deep learning based reverse image search tool for histopathology images: Similar Medical Images Like Yours (SMILY). We assessed SMILY's ability to retrieve search results in two ways: using pathologist-provided annotations, and via prospective studies where pathologists evaluated the quality of SMILY search results. As a negative control in the second evaluation, pathologists were blinded to whether search results were retrieved by SMILY or randomly. In both types of assessments, SMILY was able to retrieve search results with similar histologic features, organ site, and prostate cancer Gleason grade compared with the original query. SMILY may be a useful general-purpose tool in the pathologist's arsenal, to improve the efficiency of searching large archives of histopathology images, without the need to develop and implement specific tools for each application.
Kunal Nagpal, Davis Foote, Yun Liu, Po-Hsuan, Chen, Ellery Wulczyn, Fraser Tan, Niels Olson, Jenny L. Smith, Arash Mohtashamian, James H. Wren, Greg S. Corrado, Robert MacDonald, Lily H. Peng, Mahul B. Amin, Andrew J. Evans, Ankur R. Sangoi, Craig H. Mermel, Jason D. Hipp, Martin C. Stumpe
For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we present a deep learning system (DLS) for Gleason scoring whole-slide images of prostatectomies. Our system was developed using 112 million pathologist-annotated image patches from 1,226 slides, and evaluated on an independent validation dataset of 331 slides, where the reference standard was established by genitourinary specialist pathologists. On the validation dataset, the mean accuracy among 29 general pathologists was 0.61. The DLS achieved a significantly higher diagnostic accuracy of 0.70 (p=0.002) and trended towards better patient risk stratification in correlations to clinical follow-up data. Our approach could improve the accuracy of Gleason scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. The DLS also goes beyond the current Gleason system to more finely characterize and quantitate tumor morphology, providing opportunities for refinement of the Gleason system itself.
Boris Babenko, Ilana Traynis, Christina Chen, Preeti Singh, Akib Uddin, Jorge Cuadros, Lauren P. Daskivich, April Y. Maa, Ramasamy Kim, Eugene Yu-Chuan Kang, Yossi Matias, Greg S. Corrado, Lily Peng, Dale R. Webster, Christopher Semturs, Jonathan Krause, Avinash V. Varadarajan, Naama Hammel, Yun Liu
External eye photos were recently shown to reveal signs of diabetic retinal disease and elevated HbA1c. In this paper, we evaluate if external eye photos contain information about additional systemic medical conditions. We developed a deep learning system (DLS) that takes external eye photos as input and predicts multiple systemic parameters, such as those related to the liver (albumin, AST); kidney (eGFR estimated using the race-free 2021 CKD-EPI creatinine equation, the urine ACR); bone & mineral (calcium); thyroid (TSH); and blood count (Hgb, WBC, platelets). Development leveraged 151,237 images from 49,015 patients with diabetes undergoing diabetic eye screening in 11 sites across Los Angeles county, CA. Evaluation focused on 9 pre-specified systemic parameters and leveraged 3 validation sets (A, B, C) spanning 28,869 patients with and without diabetes undergoing eye screening in 3 independent sites in Los Angeles County, CA, and the greater Atlanta area, GA. We compared against baseline models incorporating available clinicodemographic variables (e.g. age, sex, race/ethnicity, years with diabetes). Relative to the baseline, the DLS achieved statistically significant superior performance at detecting AST>36, calcium<8.6, eGFR<60, Hgb<11, platelets<150, ACR>=300, and WBC<4 on validation set A (a patient population similar to the development sets), where the AUC of DLS exceeded that of the baseline by 5.2-19.4%. On validation sets B and C, with substantial patient population differences compared to the development sets, the DLS outperformed the baseline for ACR>=300 and Hgb<11 by 7.3-13.2%. Our findings provide further evidence that external eye photos contain important biomarkers of systemic health spanning multiple organ systems. Further work is needed to investigate whether and how these biomarkers can be translated into clinical impact.
Shawn Xu, Lin Yang, Christopher Kelly, Marcin Sieniek, Timo Kohlberger, Martin Ma, Wei-Hung Weng, Atilla Kiraly, Sahar Kazemzadeh, Zakkai Melamed, Jungyeon Park, Patricia Strachan, Yun Liu, Chuck Lau, Preeti Singh, Christina Chen, Mozziyar Etemadi, Sreenivasa Raju Kalidindi, Yossi Matias, Katherine Chou, Greg S. Corrado, Shravya Shetty, Daniel Tse, Shruthi Prabhakara, Daniel Golden, Rory Pilgrim, Krish Eswaran, Andrew Sellergren
In this work, we present an approach, which we call Embeddings for Language/Image-aligned X-Rays, or ELIXR, that leverages a language-aligned image encoder combined or grafted onto a fixed LLM, PaLM 2, to perform a broad range of chest X-ray tasks. We train this lightweight adapter architecture using images paired with corresponding free-text radiology reports from the MIMIC-CXR dataset. ELIXR achieved state-of-the-art performance on zero-shot chest X-ray (CXR) classification (mean AUC of 0.850 across 13 findings), data-efficient CXR classification (mean AUCs of 0.893 and 0.898 across five findings (atelectasis, cardiomegaly, consolidation, pleural effusion, and pulmonary edema) for 1% (~2,200 images) and 10% (~22,000 images) training data), and semantic search (0.76 normalized discounted cumulative gain (NDCG) across nineteen queries, including perfect retrieval on twelve of them). Compared to existing data-efficient methods including supervised contrastive learning (SupCon), ELIXR required two orders of magnitude less data to reach similar performance. ELIXR also showed promise on CXR vision-language tasks, demonstrating overall accuracies of 58.7% and 62.5% on visual question answering and report quality assurance tasks, respectively. These results suggest that ELIXR is a robust and versatile approach to CXR AI.
Martín Abadi, Ashish Agarwal, Paul Barham, Eugene Brevdo, Zhifeng Chen, Craig Citro, Greg S. Corrado, Andy Davis, Jeffrey Dean, Matthieu Devin, Sanjay Ghemawat, Ian Goodfellow, Andrew Harp, Geoffrey Irving, Michael Isard, Yangqing Jia, Rafal Jozefowicz, Lukasz Kaiser, Manjunath Kudlur, Josh Levenberg, Dan Mane, Rajat Monga, Sherry Moore, Derek Murray, Chris Olah, Mike Schuster, Jonathon Shlens, Benoit Steiner, Ilya Sutskever, Kunal Talwar, Paul Tucker, Vincent Vanhoucke, Vijay Vasudevan, Fernanda Viegas, Oriol Vinyals, Pete Warden, Martin Wattenberg, Martin Wicke, Yuan Yu, Xiaoqiang Zheng
TensorFlow is an interface for expressing machine learning algorithms, and an implementation for executing such algorithms. A computation expressed using TensorFlow can be executed with little or no change on a wide variety of heterogeneous systems, ranging from mobile devices such as phones and tablets up to large-scale distributed systems of hundreds of machines and thousands of computational devices such as GPU cards. The system is flexible and can be used to express a wide variety of algorithms, including training and inference algorithms for deep neural network models, and it has been used for conducting research and for deploying machine learning systems into production across more than a dozen areas of computer science and other fields, including speech recognition, computer vision, robotics, information retrieval, natural language processing, geographic information extraction, and computational drug discovery. This paper describes the TensorFlow interface and an implementation of that interface that we have built at Google. The TensorFlow API and a reference implementation were released as an open-source package under the Apache 2.0 license in November, 2015 and are available at www.tensorflow.org.
Avinash Varadarajan, Pinal Bavishi, Paisan Raumviboonsuk, Peranut Chotcomwongse, Subhashini Venugopalan, Arunachalam Narayanaswamy, Jorge Cuadros, Kuniyoshi Kanai, George Bresnick, Mongkol Tadarati, Sukhum Silpa-archa, Jirawut Limwattanayingyong, Variya Nganthavee, Joe Ledsam, Pearse A Keane, Greg S Corrado, Lily Peng, Dale R Webster
Diabetic eye disease is one of the fastest growing causes of preventable blindness. With the advent of anti-VEGF (vascular endothelial growth factor) therapies, it has become increasingly important to detect center-involved diabetic macular edema (ci-DME). However, center-involved diabetic macular edema is diagnosed using optical coherence tomography (OCT), which is not generally available at screening sites because of cost and workflow constraints. Instead, screening programs rely on the detection of hard exudates in color fundus photographs as a proxy for DME, often resulting in high false positive or false negative calls. To improve the accuracy of DME screening, we trained a deep learning model to use color fundus photographs to predict ci-DME. Our model had an ROC-AUC of 0.89 (95% CI: 0.87-0.91), which corresponds to a sensitivity of 85% at a specificity of 80%. In comparison, three retinal specialists had similar sensitivities (82-85%), but only half the specificity (45-50%, p<0.001 for each comparison with model). The positive predictive value (PPV) of the model was 61% (95% CI: 56-66%), approximately double the 36-38% by the retinal specialists. In addition to predicting ci-DME, our model was able to detect the presence of intraretinal fluid with an AUC of 0.81 (95% CI: 0.81-0.86) and subretinal fluid with an AUC of 0.88 (95% CI: 0.85-0.91). The ability of deep learning algorithms to make clinically relevant predictions that generally require sophisticated 3D-imaging equipment from simple 2D images has broad relevance to many other applications in medical imaging.
Boris Babenko, Akinori Mitani, Ilana Traynis, Naho Kitade, Preeti Singh, April Maa, Jorge Cuadros, Greg S. Corrado, Lily Peng, Dale R. Webster, Avinash Varadarajan, Naama Hammel, Yun Liu
Diabetes-related retinal conditions can be detected by examining the posterior of the eye. By contrast, examining the anterior of the eye can reveal conditions affecting the front of the eye, such as changes to the eyelids, cornea, or crystalline lens. In this work, we studied whether external photographs of the front of the eye can reveal insights into both diabetic retinal diseases and blood glucose control. We developed a deep learning system (DLS) using external eye photographs of 145,832 patients with diabetes from 301 diabetic retinopathy (DR) screening sites in one US state, and evaluated the DLS on three validation sets containing images from 198 sites in 18 other US states. In validation set A (n=27,415 patients, all undilated), the DLS detected poor blood glucose control (HbA1c > 9%) with an area under receiver operating characteristic curve (AUC) of 70.2; moderate-or-worse DR with an AUC of 75.3; diabetic macular edema with an AUC of 78.0; and vision-threatening DR with an AUC of 79.4. For all 4 prediction tasks, the DLS's AUC was higher (p<0.001) than using available self-reported baseline characteristics (age, sex, race/ethnicity, years with diabetes). In terms of positive predictive value, the predicted top 5% of patients had a 67% chance of having HbA1c > 9%, and a 20% chance of having vision threatening diabetic retinopathy. The results generalized to dilated pupils (validation set B, 5,058 patients) and to a different screening service (validation set C, 10,402 patients). Our results indicate that external eye photographs contain information useful for healthcare providers managing patients with diabetes, and may help prioritize patients for in-person screening. Further work is needed to validate these findings on different devices and patient populations (those without diabetes) to evaluate its utility for remote diagnosis and management.
Po-Hsuan Cameron Chen, Krishna Gadepalli, Robert MacDonald, Yun Liu, Kunal Nagpal, Timo Kohlberger, Jeffrey Dean, Greg S. Corrado, Jason D. Hipp, Martin C. Stumpe
The brightfield microscope is instrumental in the visual examination of both biological and physical samples at sub-millimeter scales. One key clinical application has been in cancer histopathology, where the microscopic assessment of the tissue samples is used for the diagnosis and staging of cancer and thus guides clinical therapy. However, the interpretation of these samples is inherently subjective, resulting in significant diagnostic variability. Moreover, in many regions of the world, access to pathologists is severely limited due to lack of trained personnel. In this regard, Artificial Intelligence (AI) based tools promise to improve the access and quality of healthcare. However, despite significant advances in AI research, integration of these tools into real-world cancer diagnosis workflows remains challenging because of the costs of image digitization and difficulties in deploying AI solutions. Here we propose a cost-effective solution to the integration of AI: the Augmented Reality Microscope (ARM). The ARM overlays AI-based information onto the current view of the sample through the optical pathway in real-time, enabling seamless integration of AI into the regular microscopy workflow. We demonstrate the utility of ARM in the detection of lymph node metastases in breast cancer and the identification of prostate cancer with a latency that supports real-time workflows. We anticipate that ARM will remove barriers towards the use of AI in microscopic analysis and thus improve the accuracy and efficiency of cancer diagnosis. This approach is applicable to other microscopy tasks and AI algorithms in the life sciences and beyond.
Karan Singhal, Shekoofeh Azizi, Tao Tu, S. Sara Mahdavi, Jason Wei, Hyung Won Chung, Nathan Scales, Ajay Tanwani, Heather Cole-Lewis, Stephen Pfohl, Perry Payne, Martin Seneviratne, Paul Gamble, Chris Kelly, Nathaneal Scharli, Aakanksha Chowdhery, Philip Mansfield, Blaise Aguera y Arcas, Dale Webster, Greg S. Corrado, Yossi Matias, Katherine Chou, Juraj Gottweis, Nenad Tomasev, Yun Liu, Alvin Rajkomar, Joelle Barral, Christopher Semturs, Alan Karthikesalingam, Vivek Natarajan
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.
Yun Liu, Krishna Gadepalli, Mohammad Norouzi, George E. Dahl, Timo Kohlberger, Aleksey Boyko, Subhashini Venugopalan, Aleksei Timofeev, Philip Q. Nelson, Greg S. Corrado, Jason D. Hipp, Lily Peng, Martin C. Stumpe
Each year, the treatment decisions for more than 230,000 breast cancer patients in the U.S. hinge on whether the cancer has metastasized away from the breast. Metastasis detection is currently performed by pathologists reviewing large expanses of biological tissues. This process is labor intensive and error-prone. We present a framework to automatically detect and localize tumors as small as 100 x 100 pixels in gigapixel microscopy images sized 100,000 x 100,000 pixels. Our method leverages a convolutional neural network (CNN) architecture and obtains state-of-the-art results on the Camelyon16 dataset in the challenging lesion-level tumor detection task. At 8 false positives per image, we detect 92.4% of the tumors, relative to 82.7% by the previous best automated approach. For comparison, a human pathologist attempting exhaustive search achieved 73.2% sensitivity. We achieve image-level AUC scores above 97% on both the Camelyon16 test set and an independent set of 110 slides. In addition, we discover that two slides in the Camelyon16 training set were erroneously labeled normal. Our approach could considerably reduce false negative rates in metastasis detection.
Faruk Ahmed, Andrew Sellergren, Lin Yang, Shawn Xu, Boris Babenko, Abbi Ward, Niels Olson, Arash Mohtashamian, Yossi Matias, Greg S. Corrado, Quang Duong, Dale R. Webster, Shravya Shetty, Daniel Golden, Yun Liu, David F. Steiner, Ellery Wulczyn
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.
Avinash V. Varadarajan, Ryan Poplin, Katy Blumer, Christof Angermueller, Joe Ledsam, Reena Chopra, Pearse A. Keane, Greg S. Corrado, Lily Peng, Dale R. Webster
Refractive error, one of the leading cause of visual impairment, can be corrected by simple interventions like prescribing eyeglasses. We trained a deep learning algorithm to predict refractive error from the fundus photographs from participants in the UK Biobank cohort, which were 45 degree field of view images and the AREDS clinical trial, which contained 30 degree field of view images. Our model use the "attention" method to identify features that are correlated with refractive error. Mean absolute error (MAE) of the algorithm's prediction compared to the refractive error obtained in the AREDS and UK Biobank. The resulting algorithm had a MAE of 0.56 diopters (95% CI: 0.55-0.56) for estimating spherical equivalent on the UK Biobank dataset and 0.91 diopters (95% CI: 0.89-0.92) for the AREDS dataset. The baseline expected MAE (obtained by simply predicting the mean of this population) was 1.81 diopters (95% CI: 1.79-1.84) for UK Biobank and 1.63 (95% CI: 1.60-1.67) for AREDS. Attention maps suggested that the foveal region was one of the most important areas used by the algorithm to make this prediction, though other regions also contribute to the prediction. The ability to estimate refractive error with high accuracy from retinal fundus photos has not been previously known and demonstrates that deep learning can be applied to make novel predictions from medical images. Given that several groups have recently shown that it is feasible to obtain retinal fundus photos using mobile phones and inexpensive attachments, this work may be particularly relevant in regions of the world where autorefractors may not be readily available.
Faruk Ahmed, Lin Yang, Tiam Jaroensri, Andrew Sellergren, Yossi Matias, Avinatan Hassidim, Greg S. Corrado, Dale R. Webster, Shravya Shetty, Shruthi Prabhakara, Yun Liu, Daniel Golden, Ellery Wulczyn, David F. Steiner
The interpretation of histopathology cases underlies many important diagnostic and treatment decisions in medicine. Notably, this process typically requires pathologists to integrate and summarize findings across multiple slides per case. Existing vision-language capabilities in computational pathology have so far been largely limited to small regions of interest, larger regions at low magnification, or single whole-slide images (WSIs). This limits interpretation of findings that span multiple high-magnification regions across multiple WSIs. By making use of Gemini 1.5 Flash, a large multimodal model (LMM) with a 1-million token context window, we demonstrate the ability to generate bottom-line diagnoses from up to 40,000 768x768 pixel image patches from multiple WSIs at 10X magnification. This is the equivalent of up to 11 hours of video at 1 fps. Expert pathologist evaluations demonstrate that the generated report text is clinically accurate and equivalent to or preferred over the original reporting for 68% (95% CI: [60%, 76%]) of multi-slide examples with up to 5 slides. While performance decreased for examples with 6 or more slides, this study demonstrates the promise of leveraging the long-context capabilities of modern LMMs for the uniquely challenging task of medical report generation where each case can contain thousands of image patches.
Tao Tu, Shekoofeh Azizi, Danny Driess, Mike Schaekermann, Mohamed Amin, Pi-Chuan Chang, Andrew Carroll, Chuck Lau, Ryutaro Tanno, Ira Ktena, Basil Mustafa, Aakanksha Chowdhery, Yun Liu, Simon Kornblith, David Fleet, Philip Mansfield, Sushant Prakash, Renee Wong, Sunny Virmani, Christopher Semturs, S Sara Mahdavi, Bradley Green, Ewa Dominowska, Blaise Aguera y Arcas, Joelle Barral, Dale Webster, Greg S. Corrado, Yossi Matias, Karan Singhal, Pete Florence, Alan Karthikesalingam, Vivek Natarajan
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.