Automated Annotation of Epileptiform Burden and Its Association with Outcomes.

OBJECTIVE: This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients. METHODS: A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent >16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6). RESULTS: Peak epileptiform burden was independently associated with poor outcomes (p < 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) <5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290); >10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%. INTERPRETATION: Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Predicting drug-resistant epilepsy - A machine learning approach based on administrative claims data.

Patients with drug-resistant epilepsy (DRE) are at high risk of morbidity and mortality, yet their referral to specialist care is frequently delayed. The ability to identify patients at high risk of DRE at the time of treatment initiation, and to subsequently steer their treatment pathway toward more personalized interventions, has high clinical utility. Here, we aim to demonstrate the feasibility of developing algorithms for predicting DRE using machine learning methods. Longitudinal, intersected data sourced from US pharmacy, medical, and adjudicated hospital claims from 1,376,756 patients from 2006 to 2015 were analyzed; 292,892 met inclusion criteria for epilepsy, and 38,382 were classified as having DRE using a proxy measure for drug resistance. Patients were characterized using 1270 features reflecting demographics, comorbidities, medications, procedures, epilepsy status, and payer status. Data from 175,735 randomly selected patients were used to train three algorithms and from the remainder to assess the trained models' predictive power. A model with only age and sex was used as a benchmark. The best model, random forest, achieved an area under the receiver operating characteristic curve (95% confidence interval [CI]) of 0.764 (0.759, 0.770), compared with 0.657 (0.651, 0.663) for the benchmark model. Moreover, predicted probabilities for DRE were well-calibrated with the observed frequencies in the data. The model predicted drug resistance approximately 2 years before patients in the test dataset had failed two antiepileptic drugs (AEDs). Machine learning models constructed using claims data predicted which patients are likely to fail ≥3 AEDs and are at risk of developing DRE at the time of the first AED prescription. The use of such models can ensure that patients with predicted DRE receive specialist care with potentially more aggressive therapeutic interventions from diagnosis, to help reduce the serious sequelae of DRE.

Synthetic seismocardiogram generation using a transformer-based neural network.

OBJECTIVE: To design and validate a novel deep generative model for seismocardiogram (SCG) dataset augmentation. SCG is a noninvasively acquired cardiomechanical signal used in a wide range of cardivascular monitoring tasks; however, these approaches are limited due to the scarcity of SCG data. METHODS: A deep generative model based on transformer neural networks is proposed to enable SCG dataset augmentation with control over features such as aortic opening (AO), aortic closing (AC), and participant-specific morphology. We compared the generated SCG beats to real human beats using various distribution distance metrics, notably Sliced-Wasserstein Distance (SWD). The benefits of dataset augmentation using the proposed model for other machine learning tasks were also explored. RESULTS: Experimental results showed smaller distribution distances for all metrics between the synthetically generated set of SCG and a test set of human SCG, compared to distances from an animal dataset (1.14× SWD), Gaussian noise (2.5× SWD), or other comparison sets of data. The input and output features also showed minimal error (95% limits of agreement for pre-ejection period [PEP] and left ventricular ejection time [LVET] timings are 0.03 ± 3.81 ms and -0.28 ± 6.08 ms, respectively). Experimental results for data augmentation for a PEP estimation task showed 3.3% accuracy improvement on an average for every 10% augmentation (ratio of synthetic data to real data). CONCLUSION: The model is thus able to generate physiologically diverse, realistic SCG signals with precise control over AO and AC features. This will uniquely enable dataset augmentation for SCG processing and machine learning to overcome data scarcity.

Early Prediction of Impending Exertional Heat Stroke With Wearable Multimodal Sensing and Anomaly Detection.

We employed wearable multimodal sensing (heart rate and triaxial accelerometry) with machine learning to enable early prediction of impending exertional heat stroke (EHS). US Army Rangers and Combat Engineers (N = 2,102) were instrumented while participating in rigorous 7-mile and 12-mile loaded rucksack timed marches. There were three EHS cases, and data from 478 Rangers were analyzed for model building and controls. The data-driven machine learning approach incorporated estimates of physiological strain (heart rate) and physical stress (estimated metabolic rate) trajectories, followed by reconstruction to obtain compressed representations which then fed into anomaly detection for EHS prediction. Impending EHS was predicted from 33 to 69 min before collapse. These findings demonstrate that low dimensional physiological stress to strain patterns with machine learning anomaly detection enables early prediction of impending EHS which will allow interventions that minimize or avoid pathophysiological sequelae. We describe how our approach can be expanded to other physical activities and enhanced with novel sensors.

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

BACKGROUND AND OBJECTIVES: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC. METHODS: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability. RESULTS: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds. DISCUSSION: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Quantifying Asymmetry Between Medial and Lateral Compartment Knee Loading Forces Using Acoustic Emissions.

OBJECTIVE: Osteoarthritis is the most common type of knee arthritis that can be affected by excessive and compressive loads and can affect one or more compartments of the knee: medial, lateral, and patellofemoral. The medial compartment tends to be the most vulnerable to injuries and research suggests that a better understanding of the medial to lateral load distribution conditions could provide insights to the quantitative usage of knee compartments in activities of daily life. METHODS: Prior to study in an osteoarthritic clinical population which may present with various complicating anatomical and physiological changes, we investigate knee acoustical emissions of able-bodied individuals during a varying width squat exercise which simulates loading asymmetries that would typically be seen in this clinical population. To that end, we present a novel method to quantify the directional bias of asymmetry between the medial and lateral compartment knee joint load in healthy individuals by recording knee acoustical emissions and analyzing them using a deep neural network in a subject independent model. We placed four miniature contact microphones on the medial and lateral sides of the patella on both the left and right leg. We compared the handcrafted audio features with the automated features extracted from the convolutional autoencoder which is an unsupervised model that learns the comprehensive representation of the input to determine whether these automated features can better represent the signal's characteristic in regard to the structural asymmetry of the knee joint. The input to the convolutional auto encoder (CAE) is a time-frequency representation and different types of these images such as spectrogram and scalogram are compared. We alsocompared the multi-sensor fusion approach with the performance of a single sensor to determine the robustness of using multiple sensors. RESULTS: Using a representation learning based approach, we developed a subject independent classification model capable of classifying the asymmetry of the medial and lateral joint load across subjects (accuracy = 83%). CONCLUSION: The result indicates that wavelet coherence which is the time-frequency correlation of two signals using a wavelet transform yields the best accuracy. SIGNIFICANCE: These findings suggest that acoustic signals could potentially quantify the direction of medial to lateral load distribution which would broaden the implications for wearable sensing technology for monitoring cartilage health and factors responsible for cartilage breakdown and assessing appropriate rehabilitation exercises without overloading on one side.

Wearable Seismocardiography-Based Assessment of Stroke Volume in Congenital Heart Disease.

Background Patients with congenital heart disease (CHD) are at risk for the development of low cardiac output and other physiologic derangements, which could be detected early through continuous stroke volume (SV) measurement. Unfortunately, existing SV measurement methods are limited in the clinic because of their invasiveness (eg, thermodilution), location (eg, cardiac magnetic resonance imaging), or unreliability (eg, bioimpedance). Multimodal wearable sensing, leveraging the seismocardiogram, a sternal vibration signal associated with cardiomechanical activity, offers a means to monitoring SV conveniently, affordably, and continuously. However, it has not been evaluated in a population with significant anatomical and physiological differences (ie, children with CHD) or compared against a true gold standard (ie, cardiac magnetic resonance). Here, we present the feasibility of wearable estimation of SV in a diverse CHD population (N=45 patients). Methods and Results We used our chest-worn wearable biosensor to measure baseline ECG and seismocardiogram signals from patients with CHD before and after their routine cardiovascular magnetic resonance imaging, and derived features from the measured signals, predominantly systolic time intervals, to estimate SV using ridge regression. Wearable signal features achieved acceptable SV estimation (28% error with respect to cardiovascular magnetic resonance imaging) in a held-out test set, per cardiac output measurement guidelines, with a root-mean-square error of 11.48 mL and R2 of 0.76. Additionally, we observed that using a combination of electrical and cardiomechanical features surpassed the performance of either modality alone. Conclusions A convenient wearable biosensor that estimates SV enables remote monitoring of cardiac function and may potentially help identify decompensation in patients with CHD.

Unifying the Estimation of Blood Volume Decompensation Status in a Porcine Model of Relative and Absolute Hypovolemia Via Wearable Sensing.

Hypovolemia remains the leading cause of preventable death in trauma cases. Recent research has demonstrated that using noninvasive continuous waveforms rather than traditional vital signs improves accuracy in early detection of hypovolemia to assist in triage and resuscitation. This work evaluates random forest models trained on different subsets of data from a pig model (n = 6) of absolute (bleeding) and relative (nitroglycerin-induced vasodilation) progressive hypovolemia (to 20% decrease in mean arterial pressure) and resuscitation. Features for the models were derived from a multi-modal set of wearable sensors, comprised of the electrocardiogram (ECG), seismocardiogram (SCG) and reflective photoplethysmogram (RPPG) and were normalized to each subject.s baseline. The median RMSE between predicted and actual percent progression towards cardiovascular decompensation for the best model was 30.5% during the relative period, 16.8% during absolute and 22.1% during resuscitation. The least squares best fit line over the mean aggregated predictions had a slope of 0.65 and intercept of 12.3, with an R2 value of 0.93. When transitioned to a binary classification problem to identify decompensation, this model achieved an AUROC of 0.80. This study: a) developed a global model incorporating ECG, SCG and RPPG features for estimating individual-specific decompensation from progressive relative and absolute hypovolemia and resuscitation; b) demonstrated SCG as the most important modality to predict decompensation; c) demonstrated efficacy of random forest models trained on different data subsets; and d) demonstrated adding training data from two discrete forms of hypovolemia increases prediction accuracy for the other form of hypovolemia and resuscitation.

Deep active learning for Interictal Ictal Injury Continuum EEG patterns.

OBJECTIVES: Seizures and seizure-like electroencephalography (EEG) patterns, collectively referred to as "ictal interictal injury continuum" (IIIC) patterns, are commonly encountered in critically ill patients. Automated detection is important for patient care and to enable research. However, training accurate detectors requires a large labeled dataset. Active Learning (AL) may help select informative examples to label, but the optimal AL approach remains unclear. METHODS: We assembled >200,000 h of EEG from 1,454 hospitalized patients. From these, we collected 9,808 labeled and 120,000 unlabeled 10-second EEG segments. Labels included 6 IIIC patterns. In each AL iteration, a Dense-Net Convolutional Neural Network (CNN) learned vector representations for EEG segments using available labels, which were used to create a 2D embedding map. Nearest-neighbor label spreading within the embedding map was used to create additional pseudo-labeled data. A second Dense-Net was trained using real- and pseudo-labels. We evaluated several strategies for selecting candidate points for experts to label next. Finally, we compared two methods for class balancing within queries: standard balanced-based querying (SBBQ), and high confidence spread-based balanced querying (HCSBBQ). RESULTS: Our results show: 1) Label spreading increased convergence speed for AL. 2) All query criteria produced similar results to random sampling. 3) HCSBBQ query balancing performed best. Using label spreading and HCSBBQ query balancing, we were able to train models approaching expert-level performance across all pattern categories after obtaining ∼7000 expert labels. CONCLUSION: Our results provide guidance regarding the use of AL to efficiently label large EEG datasets in critically ill patients.