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Detecting pathogen exposure during the non-symptomatic incubation period using physiological data: proof of concept in non-human primates

Summary

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices. Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device. Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures – a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation – a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001. Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host’s immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.
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Summary

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First...

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A neural network estimation of ankle torques from electromyography and accelerometry

Summary

Estimations of human joint torques can provide clinically valuable information to inform patient care, plan therapy, and assess the design of wearable robotic devices. Predicting joint torques into the future can also be useful for anticipatory robot control design. In this work, we present a method of mapping joint torque estimates and sequences of torque predictions from motion capture and ground reaction forces to wearable sensor data using several modern types of neural networks. We use dense feedforward, convolutional, neural ordinary differential equation, and long short-term memory neural networks to learn the mapping for ankle plantarflexion and dorsiflexion torque during standing,walking, running, and sprinting, and consider both single-point torque estimation, as well as the prediction of a sequence of future torques. Our results show that long short-term memory neural networks, which consider incoming data sequentially, outperform dense feedforward, neural ordinary differential equation networks, and convolutional neural networks. Predictions of future ankle torques up to 0.4 s ahead also showed strong positive correlations with the actual torques. The proposed method relies on learning from a motion capture dataset, but once the model is built, the method uses wearable sensors that enable torque estimation without the motion capture data.
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Summary

Estimations of human joint torques can provide clinically valuable information to inform patient care, plan therapy, and assess the design of wearable robotic devices. Predicting joint torques into the future can also be useful for anticipatory robot control design. In this work, we present a method of mapping joint torque...

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Detecting Parkinson's disease from wrist-worn accelerometry in the U.K. Biobank

Published in:
Sensors, Vol. 21, No. 6, 2021, Art. No. 2047.

Summary

Parkinson's disease (PD) is a chronic movement disorder that produces a variety of characteristic movement abnormalities. The ubiquity of wrist-worn accelerometry suggests a possible sensor modality for early detection of PD symptoms and subsequent tracking of PD symptom severity. As an initial proof of concept for this technological approach, we analyzed the U.K. Biobank data set, consisting of one week of wrist-worn accelerometry from a population with a PD primary diagnosis and an age-matched healthy control population. Measures of movement dispersion were extracted from automatically segmented gait data, and measures of movement dimensionality were extracted from automatically segmented low-movement data. Using machine learning classifiers applied to one week of data, PD was detected with an area under the curve (AUC) of 0.69 on gait data, AUC = 0.84 on low-movement data, and AUC = 0.85 on a fusion of both activities. It was also found that classification accuracy steadily improved across the one-week data collection, suggesting that higher accuracy could be achievable from a longer data collection. These results suggest the viability of using a low-cost and easy-to-use activity sensor for detecting movement abnormalities due to PD and motivate further research on early PD detection and tracking of PD symptom severity.
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Summary

Parkinson's disease (PD) is a chronic movement disorder that produces a variety of characteristic movement abnormalities. The ubiquity of wrist-worn accelerometry suggests a possible sensor modality for early detection of PD symptoms and subsequent tracking of PD symptom severity. As an initial proof of concept for this technological approach, we...

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Using oculomotor features to predict changes in optic nerve sheath diameter and ImPACT scores from contact-sport athletes

Summary

There is mounting evidence linking the cumulative effects of repetitive head impacts to neuro-degenerative conditions. Robust clinical assessment tools to identify mild traumatic brain injuries are needed to assist with timely diagnosis for return-to-field decisions and appropriately guide rehabilitation. The focus of the present study is to investigate the potential for oculomotor features to complement existing diagnostic tools, such as measurements of Optic Nerve Sheath Diameter (ONSD) and Immediate Post-concussion Assessment and Cognitive Testing (ImPACT). Thirty-one high school American football and soccer athletes were tracked through the course of a sports season. Given the high risk of repetitive head impacts associated with both soccer and football, our hypotheses were that (1) ONSD and ImPACT scores would worsen through the season and (2) oculomotor features would effectively capture both neurophysiological changes reflected by ONSD and neuro-functional status assessed via ImPACT. Oculomotor features were used as input to Linear Mixed-Effects Regression models to predict ONSD and ImPACT scores as outcomes. Prediction accuracy was evaluated to identify explicit relationships between eye movements, ONSD, and ImPACT scores. Significant Pearson correlations were observed between predicted and actual outcomes for ONSD (Raw = 0.70; Normalized = 0.45) and for ImPACT (Raw = 0.86; Normalized = 0.71), demonstrating the capability of oculomotor features to capture neurological changes detected by both ONSD and ImPACT. The most predictive features were found to relate to motor control and visual-motor processing. In future work, oculomotor models, linking neural structures to oculomotor function, can be built to gain extended mechanistic insights into neurophysiological changes observed through seasons of participation in contact sports.
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Summary

There is mounting evidence linking the cumulative effects of repetitive head impacts to neuro-degenerative conditions. Robust clinical assessment tools to identify mild traumatic brain injuries are needed to assist with timely diagnosis for return-to-field decisions and appropriately guide rehabilitation. The focus of the present study is to investigate the potential...

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Speaker separation in realistic noise environments with applications to a cognitively-controlled hearing aid

Summary

Future wearable technology may provide for enhanced communication in noisy environments and for the ability to pick out a single talker of interest in a crowded room simply by the listener shifting their attentional focus. Such a system relies on two components, speaker separation and decoding the listener's attention to acoustic streams in the environment. To address the former, we present a system for joint speaker separation and noise suppression, referred to as the Binaural Enhancement via Attention Masking Network (BEAMNET). The BEAMNET system is an end-to-end neural network architecture based on self-attention. Binaural input waveforms are mapped to a joint embedding space via a learned encoder, and separate multiplicative masking mechanisms are included for noise suppression and speaker separation. Pairs of output binaural waveforms are then synthesized using learned decoders, each capturing a separated speaker while maintaining spatial cues. A key contribution of BEAMNET is that the architecture contains a separation path, an enhancement path, and an autoencoder path. This paper proposes a novel loss function which simultaneously trains these paths, so that disabling the masking mechanisms during inference causes BEAMNET to reconstruct the input speech signals. This allows dynamic control of the level of suppression applied by BEAMNET via a minimum gain level, which is not possible in other state-of-the-art approaches to end-to-end speaker separation. This paper also proposes a perceptually-motivated waveform distance measure. Using objective speech quality metrics, the proposed system is demonstrated to perform well at separating two equal-energy talkers, even in high levels of background noise. Subjective testing shows an improvement in speech intelligibility across a range of noise levels, for signals with artificially added head-related transfer functions and background noise. Finally, when used as part of an auditory attention decoder (AAD) system using existing electroencephalogram (EEG) data, BEAMNET is found to maintain the decoding accuracy achieved with ideal speaker separation, even in severe acoustic conditions. These results suggest that this enhancement system is highly effective at decoding auditory attention in realistic noise environments, and could possibly lead to improved speech perception in a cognitively controlled hearing aid.
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Summary

Future wearable technology may provide for enhanced communication in noisy environments and for the ability to pick out a single talker of interest in a crowded room simply by the listener shifting their attentional focus. Such a system relies on two components, speaker separation and decoding the listener's attention to...

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Ablation analysis to select wearable sensors for classifying standing, walking, and running

Summary

The field of human activity recognition (HAR) often utilizes wearable sensors and machine learning techniques in order to identify the actions of the subject. This paper considers the activity recognition of walking and running while using a support vector machine (SVM) that was trained on principal components derived from wearable sensor data. An ablation analysis is performed in order to select the subset of sensors that yield the highest classification accuracy. The paper also compares principal components across trials to inform the similarity of the trials. Five subjects were instructed to perform standing, walking, running, and sprinting on a self-paced treadmill, and the data were recorded while using surface electromyography sensors (sEMGs), inertial measurement units (IMUs), and force plates. When all of the sensors were included, the SVM had over 90% classification accuracy using only the first three principal components of the data with the classes of stand, walk, and run/sprint (combined run and sprint class). It was found that sensors that were placed only on the lower leg produce higher accuracies than sensors placed on the upper leg. There was a small decrease in accuracy when the force plates are ablated, but the difference may not be operationally relevant. Using only accelerometers without sEMGs was shown to decrease the accuracy of the SVM.
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Summary

The field of human activity recognition (HAR) often utilizes wearable sensors and machine learning techniques in order to identify the actions of the subject. This paper considers the activity recognition of walking and running while using a support vector machine (SVM) that was trained on principal components derived from wearable...

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Ankle torque estimation during locomotion from surface electromyography and accelerometry

Published in:
2020 8th IEEE Intl. Conf. on Biomedical Robotics and Biomechatronics, BioRob, 29 November - 1 December 2020.

Summary

Estimations of human joint torques can provide quantitative, clinically valuable information to inform patient care, plan therapy, and assess the design of wearable robotic devices. Standard methods for estimating joint torques are limited to laboratory or clinical settings since they require expensive equipment to measure joint kinematics and ground reaction forces. Wearable sensor data combined with neural networks may offer a less expensive and obtrusive estimation method.We present a method of mapping joint torque estimates obtained from motion capture and ground reaction forces to wearable sensor data. We use several different neural networks to learn the torque mapping for the ankle joints during standing, walking, running, and sprinting. Our results show that neural networks that consider time (recurrent and long short-term memory networks) outperform feedforward network architectures, producing results in the range of 0.005-0.008 N m/kg mean squared error (MSE) when compared to the inverse dynamics model on which it was trained. As a point of reference, the typical measurement errors from inverse dynamics models are in the range of 0.0004-0.0064 N m/kg MSE. Errors tended to increase with locomotion speed, with the highest errors during sprinting and the lowest during standing or walking. Future work may investigate model generalizability across sensor placements, subjects, locomotion variants, and usage duration. The proposed method relies on learning from a motion capture dataset, but once the model is built, the method uses wearable sensors that enable torque estimation without the motion capture data. These methods also have potential uses for the design and testing of wearable robotic systems outside of a laboratory environment.
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Summary

Estimations of human joint torques can provide quantitative, clinically valuable information to inform patient care, plan therapy, and assess the design of wearable robotic devices. Standard methods for estimating joint torques are limited to laboratory or clinical settings since they require expensive equipment to measure joint kinematics and ground reaction...

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Ultrasound and artificial intelligence

Published in:
Chapter 8 in Machine Learning in Cardiovascular Medicine, 2020, pp. 177-210.

Summary

Compared to other major medical imaging modalities such as X-ray, computed tomography (CT), and magnetic resonance imaging, medical ultrasound (US) has unique attributes that make it the preferred modality for many clinical applications. In particular, US is nonionizing, portable, and provides real-time imaging, with adequate spatial and depth resolution to visualize tissue dynamics. The ability to measure Doppler information is also important, particularly for measuring blood flows. The small size of US transducers is a key attribute for intravascular applications. In addition, accessibility has been increased with the use of portable US, which continues to move toward a smaller footprint and lower cost. Nowadays, some US probes can even be directly connected to a phone or tablet. On the other hand, US also has unique challenges, particularly in that image quality is highly dependent on the operator’s skill in acquiring images based on the proper position, orientation, and probe pressure. Additional challenges that further require operator skill include the presence of noise, artifacts, limited field of view, difficulty in imaging structures behind bone and air, and device variability across manufacturers. Sonographers become highly proficient through extensive training and long experience, but high intra- and interobserver variability remains. This skill dependence has limited the wider use of US by healthcare providers who are not US imaging specialists. Recent advances in machine learning (ML) have been increasingly applied to medical US (Brattain, Telfer, Dhyani, Grajo, & Samir, 2018), with a goal of reducing intra- and interobserver variability as well as interpretation time. As progress toward these goals is made, US use by nonspecialists is expected to proliferate, including nurses at the bedside or medics in the field. The acceleration in ML applications for medical US can be seen from the increasing number of publications (Fig. 8.1) and Food and Drug Administration (FDA) approvals (Table 8.1) in the past few years. Fig. 8.1 shows that cardiovascular applications (spanning the heart, brain and vessels) have received the most attention, compared to other organs. Table 8.1 shows that pace of US FDA-cleared artificial intelligence (AI) products that combine AI and ultrasound is accelerating. Of note, many of the products have been approved over the last couple of years. Companies such as Butterfly Network (Guilford, CT) have also demonstrated AI-driven applications for portable ultrasound and more FDA clearances are expected to be published. The goals of this chapter are to highlight the recent progress, as well as the current challenges and future opportunities. Specifically, this chapter addresses topics such as the following: (1) what is the current state of machine learning for medical US application, both in research and commercially; (2) what applications are receiving the most attention and have performance improvements been quantified; (3) how do ML solutions fit in an overall workflow; and (4) what open-source datasets are available for the broader community to contribute to progress in this field. The focus is on cardiovascular applications (Section Cardiovascular/echocardiography), but common themes and differences for other applications for medical US are also summarized (Section Breast, liver, and thyroid ultrasound). A discussion is offered in Discussion and outlook section.
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Summary

Compared to other major medical imaging modalities such as X-ray, computed tomography (CT), and magnetic resonance imaging, medical ultrasound (US) has unique attributes that make it the preferred modality for many clinical applications. In particular, US is nonionizing, portable, and provides real-time imaging, with adequate spatial and depth resolution to...

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Image processing pipeline for liver fibrosis classification using ultrasound shear wave elastography

Published in:
Ultrasound in Med. & Biol., Vol. 46, No. 10, October 2020, pp. 2667-2676.

Summary

The purpose of this study was to develop an automated method for classifying liver fibrosis stage >=F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each of eight or more SWE images, computing the mean tissue stiffness within each of the regions of interest and computing a resulting stiffness value as the median of the means. The 527-subject database consisted of 5526 SWE images and pathologist-scored biopsies, with data collected from a single system at a single site. The automated method integrates three modules that assess SWE image quality, select a region of interest from each SWE measurement and perform machine learning-based, multi-image SWE classification for fibrosis stage >=F2. Several classification methods were developed and tested using fivefold cross-validation with training, validation and test sets partitioned by subject. Performance metrics were area under receiver operating characteristic curve (AUROC), specificity at 95% sensitivity and number of SWE images required. The final automated method yielded an AUROC of 0.93 (95% confidence interval: 0.90-0.94) versus 0.69 (95% confidence interval: 0.65-0.72) for the reference method, 71% specificity with 95% sensitivity versus 5% and four images per decision versus eight or more. In conclusion, the automated method reported in this study significantly improved the accuracy for >=F2 classification of SWE measurements as well as reduced the number of measurements needed, which has the potential to reduce clinical workflow.
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Summary

The purpose of this study was to develop an automated method for classifying liver fibrosis stage >=F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each...

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Human balance models optimized using a large-scale, parallel architecture with applications to mild traumatic brain injury

Published in:
2020 IEEE High Performance Extreme Computing Conf., HPEC, 22-24 September 2020.

Summary

Static and dynamic balance are frequently disrupted through brain injuries. The impairment can be complex and for mild traumatic brain injury (mTBI) can be undetectable by standard clinical tests. Therefore, neurologically relevant modeling approaches are needed for detection and inference of mechanisms of injury. The current work presents models of static and dynamic balance that have a high degree of correspondence. Emphasizing structural similarity between the domains facilitates development of both. Furthermore, particular attention is paid to components of sensory feedback and sensory integration to ground mechanisms in neurobiology. Models are adapted to fit experimentally collected data from 10 healthy control volunteers and 11 mild traumatic brain injury volunteers. Through an analysis by synthesis approach whose implementation was made possible by a state-of-the-art high performance computing system, we derived an interpretable, model based feature set that could classify mTBI and controls in a static balance task with an ROC AUC of 0.72.
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Summary

Static and dynamic balance are frequently disrupted through brain injuries. The impairment can be complex and for mild traumatic brain injury (mTBI) can be undetectable by standard clinical tests. Therefore, neurologically relevant modeling approaches are needed for detection and inference of mechanisms of injury. The current work presents models of...

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