Towards Conversational Diagnostic AI

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

Towards trustworthy seizure onset detection using workflow notes

A major barrier to deploying healthcare AI models is their trustworthiness. One form of trustworthiness is a model's robustness across different subgroups: while existing models may exhibit expert-level performance on aggregate metrics, they often rely on non-causal features, leading to errors in hidden subgroups. To take a step closer towards trustworthy seizure onset detection from EEG, we propose to leverage annotations that are produced by healthcare personnel in routine clinical workflows -- which we refer to as workflow notes -- that include multiple event descriptions beyond seizures. Using workflow notes, we first show that by scaling training data to an unprecedented level of 68,920 EEG hours, seizure onset detection performance significantly improves (+12.3 AUROC points) compared to relying on smaller training sets with expensive manual gold-standard labels. Second, we reveal that our binary seizure onset detection model underperforms on clinically relevant subgroups (e.g., up to a margin of 6.5 AUROC points between pediatrics and adults), while having significantly higher false positives on EEG clips showing non-epileptiform abnormalities compared to any EEG clip (+19 FPR points). To improve model robustness to hidden subgroups, we train a multilabel model that classifies 26 attributes other than seizures, such as spikes, slowing, and movement artifacts. We find that our multilabel model significantly improves overall seizure onset detection performance (+5.9 AUROC points) while greatly improving performance among subgroups (up to +8.3 AUROC points), and decreases false positives on non-epileptiform abnormalities by 8 FPR points. Finally, we propose a clinical utility metric based on false positives per 24 EEG hours and find that our multilabel model improves this clinical utility metric by a factor of 2x across different clinical settings.

The Importance of Background Information for Out of Distribution Generalization

Domain generalization in medical image classification is an important problem for trustworthy machine learning to be deployed in healthcare. We find that existing approaches for domain generalization which utilize ground-truth abnormality segmentations to control feature attributions have poor out-of-distribution (OOD) performance relative to the standard baseline of empirical risk minimization (ERM). We investigate what regions of an image are important for medical image classification and show that parts of the background, that which is not contained in the abnormality segmentation, provides helpful signal. We then develop a new task-specific mask which covers all relevant regions. Utilizing this new segmentation mask significantly improves the performance of the existing methods on the OOD test sets. To obtain better generalization results than ERM, we find it necessary to scale up the training data size in addition to the usage of these task-specific masks.

Domino: Discovering Systematic Errors with Cross-Modal Embeddings

Machine learning models that achieve high overall accuracy often make systematic errors on important subsets (or slices) of data. Identifying underperforming slices is particularly challenging when working with high-dimensional inputs (e.g. images, audio), where important slices are often unlabeled. In order to address this issue, recent studies have proposed automated slice discovery methods (SDMs), which leverage learned model representations to mine input data for slices on which a model performs poorly. To be useful to a practitioner, these methods must identify slices that are both underperforming and coherent (i.e. united by a human-understandable concept). However, no quantitative evaluation framework currently exists for rigorously assessing SDMs with respect to these criteria. Additionally, prior qualitative evaluations have shown that SDMs often identify slices that are incoherent. In this work, we address these challenges by first designing a principled evaluation framework that enables a quantitative comparison of SDMs across 1,235 slice discovery settings in three input domains (natural images, medical images, and time-series data). Then, motivated by the recent development of powerful cross-modal representation learning approaches, we present Domino, an SDM that leverages cross-modal embeddings and a novel error-aware mixture model to discover and describe coherent slices. We find that Domino accurately identifies 36% of the 1,235 slices in our framework - a 12 percentage point improvement over prior methods. Further, Domino is the first SDM that can provide natural language descriptions of identified slices, correctly generating the exact name of the slice in 35% of settings.

Combining Recurrent, Convolutional, and Continuous-time Models with Linear State-Space Layers

Recurrent neural networks (RNNs), temporal convolutions, and neural differential equations (NDEs) are popular families of deep learning models for time-series data, each with unique strengths and tradeoffs in modeling power and computational efficiency. We introduce a simple sequence model inspired by control systems that generalizes these approaches while addressing their shortcomings. The Linear State-Space Layer (LSSL) maps a sequence $u \mapsto y$ by simply simulating a linear continuous-time state-space representation $\dot{x} = Ax + Bu, y = Cx + Du$. Theoretically, we show that LSSL models are closely related to the three aforementioned families of models and inherit their strengths. For example, they generalize convolutions to continuous-time, explain common RNN heuristics, and share features of NDEs such as time-scale adaptation. We then incorporate and generalize recent theory on continuous-time memorization to introduce a trainable subset of structured matrices $A$ that endow LSSLs with long-range memory. Empirically, stacking LSSL layers into a simple deep neural network obtains state-of-the-art results across time series benchmarks for long dependencies in sequential image classification, real-world healthcare regression tasks, and speech. On a difficult speech classification task with length-16000 sequences, LSSL outperforms prior approaches by 24 accuracy points, and even outperforms baselines that use hand-crafted features on 100x shorter sequences.

Automated Seizure Detection and Seizure Type Classification From Electroencephalography With a Graph Neural Network and Self-Supervised Pre-Training

Automated seizure detection and classification from electroencephalography (EEG) can greatly improve the diagnosis and treatment of seizures. While prior studies mainly used convolutional neural networks (CNNs) that assume image-like structure in EEG signals or spectrograms, this modeling choice does not reflect the natural geometry of or connectivity between EEG electrodes. In this study, we propose modeling EEGs as graphs and present a graph neural network for automated seizure detection and classification. In addition, we leverage unlabeled EEG data using a self-supervised pre-training strategy. Our graph model with self-supervised pre-training significantly outperforms previous state-of-the-art CNN and Long Short-Term Memory (LSTM) models by 6.3 points (7.8%) in Area Under the Receiver Operating Characteristic curve (AUROC) for seizure detection and 6.3 points (9.2%) in weighted F1-score for seizure type classification. Ablation studies show that our graph-based modeling approach significantly outperforms existing CNN or LSTM models, and that self-supervision helps further improve the model performance. Moreover, we find that self-supervised pre-training substantially improves model performance on combined tonic seizures, a low-prevalence seizure type. Furthermore, our model interpretability analysis suggests that our model is better at identifying seizure regions compared to an existing CNN. In summary, our graph-based modeling approach integrates domain knowledge about EEG, sets a new state-of-the-art for seizure detection and classification on a large public dataset (5,499 EEG files), and provides better ability to identify seizure regions.

Inaccurate Supervision of Neural Networks with Incorrect Labels: Application to Epilepsy

This work describes multiple weak supervision strategies for video processing with neural networks in the context of seizure detection. To study seizure onset, we have designed automated methods to detect seizures from electroencephalography (EEG), a modality used for recording electrical brain activity. However, the EEG signal alone is sometimes not enough for existing detection methods to discriminate seizure from artifacts having a similar signal on EEG. For example, such artifacts could be triggered by patting, rocking or suctioning in the case of neonates. In this article, we addressed this problem by automatically detecting an example artifact -- patting of neonates -- from continuous video recordings of neonates acquired during clinical routine. We computed frame-to-frame cross-correlation matrices to isolate patterns showing repetitive movements indicative of patting of the patient. Next, a convolutional neural network was trained to classify whether these matrices contained patting events using weak training labels -- noisy labels generated during daily clinical procedure. The labels were considered weak as they were sometimes incorrect. We investigated whether networks trained with more samples, containing more uncertain and weak labels, could achieve a higher performance. Our results showed that, in the case of patting detection, such networks could achieve a higher recall, without sacrificing precision. These networks focused on areas of the cross-correlation matrices that were more meaningful to the task. More generally, our work gives insights into building more accurate models from weakly labelled time sequences.

Cross-Modal Data Programming Enables Rapid Medical Machine Learning

Labeling training datasets has become a key barrier to building medical machine learning models. One strategy is to generate training labels programmatically, for example by applying natural language processing pipelines to text reports associated with imaging studies. We propose cross-modal data programming, which generalizes this intuitive strategy in a theoretically-grounded way that enables simpler, clinician-driven input, reduces required labeling time, and improves with additional unlabeled data. In this approach, clinicians generate training labels for models defined over a target modality (e.g. images or time series) by writing rules over an auxiliary modality (e.g. text reports). The resulting technical challenge consists of estimating the accuracies and correlations of these rules; we extend a recent unsupervised generative modeling technique to handle this cross-modal setting in a provably consistent way. Across four applications in radiography, computed tomography, and electroencephalography, and using only several hours of clinician time, our approach matches or exceeds the efficacy of physician-months of hand-labeling with statistical significance, demonstrating a fundamentally faster and more flexible way of building machine learning models in medicine.