Ridwan Alam

Aniruddh Raghu, Payal Chandak, Ridwan Alam et al.

Self-supervised learning (SSL) for clinical time series data has received significant attention in recent literature, since these data are highly rich and provide important information about a patient's physiological state. However, most existing SSL methods for clinical time series are limited in that they are designed for unimodal time series, such as a sequence of structured features (e.g., lab values and vitals signs) or an individual high-dimensional physiological signal (e.g., an electrocardiogram). These existing methods cannot be readily extended to model time series that exhibit multimodality, with structured features and high-dimensional data being recorded at each timestep in the sequence. In this work, we address this gap and propose a new SSL method -- Sequential Multi-Dimensional SSL -- where a SSL loss is applied both at the level of the entire sequence and at the level of the individual high-dimensional data points in the sequence in order to better capture information at both scales. Our strategy is agnostic to the specific form of loss function used at each level -- it can be contrastive, as in SimCLR, or non-contrastive, as in VICReg. We evaluate our method on two real-world clinical datasets, where the time series contains sequences of (1) high-frequency electrocardiograms and (2) structured data from lab values and vitals signs. Our experimental results indicate that pre-training with our method and then fine-tuning on downstream tasks improves performance over baselines on both datasets, and in several settings, can lead to improvements across different self-supervised loss functions.

Ridwan Alam, Collin Stultz

The diagnosis, prognosis, and treatment of a number of cardiovascular disorders rely on ECG interval measurements, including the PR, QRS, and QT intervals. These quantities are measured from the 12-lead ECG, either manually or using automated algorithms, which are readily available in clinical settings. A number of wearable devices, however, can acquire the lead-I ECG in an outpatient setting, thereby raising the potential for out-of-hospital monitoring for disorders that involve clinically significant changes in ECG intervals. In this work, we therefore developed a series of deep learning models for estimating the PR, QRS, and QT intervals using lead-I ECG. From a corpus of 4.2 million ECGs from patients at the Massachusetts General Hospital, we train and validate each of the models. At internal holdout validation, we achieve mean absolute errors (MAE) of 6.3 ms for QRS durations and 11.9 ms for QT intervals, and an MAE of 9.2 ms for estimating PR intervals. Moreover, as a well-defined P-wave does not always exist in ECG tracings - for example, when there is atrial fibrillation - we trained a model that can identify when there is a P-wave, and consequently, a measurable PR interval. We validate our models on three large external healthcare datasets without any finetuning or retraining - 3.2 million ECG from the Brigham and Womens Hospital, 668 thousand from MIMIC-IV, and 20 thousand from PTB-XL - and achieve similar performance. Also, our models significantly outperform two publicly available baseline algorithms. This work demonstrates that ECG intervals can be tracked from only lead-I ECG using deep learning, and highlights the potential for out-of-hospital applications.

Ridwan Alam, Aaron Aguirre, Collin Stultz

For a number of antiarrhythmics, drug loading requires a 3 day hospitalization with monitoring for QT prolongation. Automated QT monitoring with wearable ECG monitors would facilitate out-of-hospital care. We develop a deep learning model that infers QT intervals from ECG lead-I - the lead most often acquired from ambulatory ECG monitors - and to use this model to detect clinically meaningful QT-prolongation episodes during Dofetilide drug loading. Using 4.22 million 12-lead ECG recordings from 903.6 thousand patients at the Massachusetts General Hospital, we develop a deep learning model, QTNet, that infers QT intervals from lead-I. Over 3 million ECGs from 653 thousand patients are used to train the model and an internal-test set containing 633 thousand ECGs from 135 thousand patients was used for testing. QTNet is further evaluated on an external-validation set containing 3.1 million ECGs from 667 thousand patients at another institution. QTNet was used to detect Dofetilide-induced QT prolongation in a publicly available database (ECGRDVQ-dataset) containing ECGs from subjects enrolled in a clinical trial evaluating the effects of antiarrhythmic drugs. QTNet achieves mean absolute errors of 12.63ms (internal-test) and 12.30ms (external-validation) for estimating absolute QT intervals. The associated Pearson correlation coefficients are 0.91 (internal-test) and 0.92 (external-validation). For the ECGRDVQ-dataset, QTNet detects Dofetilide-induced QTc prolongation with 87% sensitivity and 77% specificity. The negative predictive value of the model is greater than 95% when the pre-test probability of drug-induced QTc prolongation is below 25%. Drug-induced QT prolongation risk can be tracked from ECG lead-I using deep learning.

Ramin Nateghi, Ruoji Zhou, Madeline Saft et al.

Artificial intelligence may assist healthcare systems in meeting increasing demand for pathology services while maintaining diagnostic quality and reducing turnaround time and costs. We aimed to investigate the performance of an institutionally developed system for prostate cancer detection, grading, and workflow optimization and to contrast this with commercial alternatives. From August 2021 to March 2023, we scanned 21,396 slides from 1,147 patients receiving prostate biopsy. We developed models for cancer detection, grading, and screening of equivocal cases for IHC ordering. We compared the performance of task-specific prostate models with general-purpose foundation models in a prospectively collected dataset that reflects our patient population. We also evaluated the contributions of a bespoke model designed to improve sensitivity to small cancer foci and perception of low-resolution patterns. We found high concordance with pathologist ground-truth in detection (area under curve 98.5%, sensitivity 95.0%, and specificity 97.8%), ISUP grading (Cohen's kappa 0.869), grade group 3 or higher classification (area under curve 97.5%, sensitivity 94.9%, specificity 96.6%). Screening models could correctly classify 55% of biopsy blocks where immunohistochemistry was ordered with a 1.4% error rate. No statistically significant differences were observed between task-specific and foundation models in cancer detection, although the task-specific model is significantly smaller and faster. Institutions like academic medical centers that have high scanning volumes and report abstraction capabilities can develop highly accurate computational pathology models for internal use. These models have the potential to aid in quality control role and to improve resource allocation and workflow in the pathology lab to help meet future challenges in prostate cancer diagnosis.

Ridwan Alam, David B. Peden, John C. Lach

Breathing rate (BR), minute ventilation (VE), and other respiratory parameters are essential for real-time patient monitoring in many acute health conditions, such as asthma. The clinical standard for measuring respiration, namely Spirometry, is hardly suitable for continuous use. Wearables can track many physiological signals, like ECG and motion, yet not respiration. Deriving respiration from other modalities has become an area of active research. In this work, we infer respiratory parameters from wearable ECG and wrist motion signals. We propose a modular and generalizable classification-regression pipeline to utilize available context information, such as physical activity, in learning context-conditioned inference models. Morphological and power domain novel features from the wearable ECG are extracted to use with these models. Exploratory feature selection methods are incorporated in this pipeline to discover application-specific interpretable biomarkers. Using data from 15 subjects, we evaluate two implementations of the proposed pipeline: for inferring BR and VE. Each implementation compares generalized linear model, random forest, support vector machine, Gaussian process regression, and neighborhood component analysis as contextual regression models. Permutation, regularization, and relevance determination methods are used to rank the ECG features to identify robust ECG biomarkers across models and activities. This work demonstrates the potential of wearable sensors not only in continuous monitoring, but also in designing biomarker-driven preventive measures.