Abstract
For newly diagnosed breast cancer, estrogen receptor status (ERS) is a key molecular marker used for prognosis and treatment decisions. During clinical management, ERS is determined by ...pathologists from immunohistochemistry (IHC) staining of biopsied tissue for the targeted receptor, which highlights the presence of cellular surface antigens. This is an expensive, time-consuming process which introduces discordance in results due to variability in IHC preparation and pathologist subjectivity. In contrast, hematoxylin and eosin (H&E) staining—which highlights cellular morphology—is quick, less expensive, and less variable in preparation. Here we show that machine learning can determine molecular marker status, as assessed by hormone receptors, directly from cellular morphology. We develop a multiple instance learning-based deep neural network that determines ERS from H&E-stained whole slide images (WSI). Our algorithm—trained strictly with WSI-level annotations—is accurate on a varied, multi-country dataset of 3,474 patients, achieving an area under the curve (AUC) of 0.92 for sensitivity and specificity. Our approach has the potential to augment clinicians’ capabilities in cancer prognosis and theragnosis by harnessing biological signals imperceptible to the human eye.
A decade of unprecedented progress in artificial intelligence (AI) has demonstrated the potential for many fields-including medicine-to benefit from the insights that AI techniques can extract from ...data. Here we survey recent progress in the development of modern computer vision techniques-powered by deep learning-for medical applications, focusing on medical imaging, medical video, and clinical deployment. We start by briefly summarizing a decade of progress in convolutional neural networks, including the vision tasks they enable, in the context of healthcare. Next, we discuss several example medical imaging applications that stand to benefit-including cardiology, pathology, dermatology, ophthalmology-and propose new avenues for continued work. We then expand into general medical video, highlighting ways in which clinical workflows can integrate computer vision to enhance care. Finally, we discuss the challenges and hurdles required for real-world clinical deployment of these technologies.
Microscopy is a central method in life sciences. Many popular methods, such as antibody labeling, are used to add physical fluorescent labels to specific cellular constituents. However, these ...approaches have significant drawbacks, including inconsistency; limitations in the number of simultaneous labels because of spectral overlap; and necessary perturbations of the experiment, such as fixing the cells, to generate the measurement. Here, we show that a computational machine-learning approach, which we call “in silico labeling” (ISL), reliably predicts some fluorescent labels from transmitted-light images of unlabeled fixed or live biological samples. ISL predicts a range of labels, such as those for nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because prediction happens in silico, the method is consistent, is not limited by spectral overlap, and does not disturb the experiment. ISL generates biological measurements that would otherwise be problematic or impossible to acquire.
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•Fluorescence microscopy images can be predicted from transmitted-light z stacks•7 fluorescent labels were validated across three labs, modalities, and cell types•New labels can be predicted using minimal additional training data
In silico labeling, a machine-learning approach, reliably infers fluorescent measurements from transmitted-light images of unlabeled fixed or live biological samples.
The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More ...recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.
The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance ...has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.
The COVID-19 global pandemic has resulted in international efforts to understand, track, and mitigate the disease, yielding a significant corpus of COVID-19 and SARS-CoV-2-related publications across ...scientific disciplines. Throughout 2020, over 400,000 coronavirus-related publications have been collected through the COVID-19 Open Research Dataset. Here, we present CO-Search, a semantic, multi-stage, search engine designed to handle complex queries over the COVID-19 literature, potentially aiding overburdened health workers in finding scientific answers and avoiding misinformation during a time of crisis. CO-Search is built from two sequential parts: a hybrid semantic-keyword retriever, which takes an input query and returns a sorted list of the 1000 most relevant documents, and a re-ranker, which further orders them by relevance. The retriever is composed of a deep learning model (Siamese-BERT) that encodes query-level meaning, along with two keyword-based models (BM25, TF-IDF) that emphasize the most important words of a query. The re-ranker assigns a relevance score to each document, computed from the outputs of (1) a question-answering module which gauges how much each document answers the query, and (2) an abstractive summarization module which determines how well a query matches a generated summary of the document. To account for the relatively limited dataset, we develop a text augmentation technique which splits the documents into pairs of paragraphs and the citations contained in them, creating millions of (citation title, paragraph) tuples for training the retriever. We evaluate our system ( http://einstein.ai/covid ) on the data of the TREC-COVID information retrieval challenge, obtaining strong performance across multiple key information retrieval metrics.
The CONSORT 2010 statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More ...recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders), and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human–AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.
Since its inception in 2017,
has attracted a disproportionate number of manuscripts reporting on uses of artificial intelligence. This field has matured rapidly in the past several years. There was ...initial fascination with the algorithms themselves (machine learning, deep learning, convoluted neural networks) and the use of these algorithms to make predictions that often surpassed prevailing benchmarks. As the discipline has matured, individuals have called attention to aberrancies in the output of these algorithms. In particular, criticisms have been widely circulated that algorithmically developed models may have limited generalizability due to overfitting to the training data and may systematically perpetuate various forms of biases inherent in the training data, including race, gender, age, and health state or fitness level (Challen et al. BMJ Qual. Saf. 28:231-237, 2019; O'neil. Weapons of Math Destruction: How Big Data Increases Inequality and Threatens Democracy, Broadway Book, 2016). Given our interest in publishing the highest quality papers and the growing volume of submissions using AI algorithms, we offer a list of criteria that authors should consider before submitting papers to
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Abstract
Biology has become a prime area for the deployment of deep learning and artificial intelligence (AI), enabled largely by the massive data sets that the field can generate. Key to most AI ...tasks is the availability of a sufficiently large, labeled data set with which to train AI models. In the context of microscopy, it is easy to generate image data sets containing millions of cells and structures. However, it is challenging to obtain large-scale high-quality annotations for AI models. Here, we present HALS (Human-Augmenting Labeling System), a human-in-the-loop data labeling AI, which begins uninitialized and learns annotations from a human, in real-time. Using a multi-part AI composed of three deep learning models, HALS learns from just a few examples and immediately decreases the workload of the annotator, while increasing the quality of their annotations. Using a highly repetitive use-case—annotating cell types—and running experiments with seven pathologists—experts at the microscopic analysis of biological specimens—we demonstrate a manual work reduction of 90.60%, and an average data-quality boost of 4.34%, measured across four use-cases and two tissue stain types.
...if malignant lesion training images contain the markers or rulers used by dermatologists to measure lesion diameters but benign lesion training images never do, then algorithms may learn that the ...presence of a marker implies the presence of cancer, leading to a drop in true performance. Here, the challenge lies not only in identifying the type of condition (eg, psoriasis vs eczema) but also in usefully quantifying change over time so that algorithms can help patients and providers understand the effectiveness of treatments. Primary care doctors would be able to use a deep learning-enhanced smartphone app to screen patients for skin cancer during routine visits.
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