Morphological Variability Analysis of Physiologic Waveform for Prediction and Detection of Diseases

For many years it has been known that variability of the morphology of high-resolution (∼30-1000 Hz) physiological time series data provides additional prognostic value over lower resolution (≤ 1Hz) derived averages such as heart rate (HR), breathing rate (BR) and blood pressure (BP). However, the field has remained rather ad hoc, based on hand-crafted features. Using a model-based approach we explore the nature of these features and their sensitivity to variabilities introduced by changes in both the sampling period (HR) and observational reference frame (through breathing). HR and BR are determined as having a statistically significant confounding effect on the morphological variability (MV) evaluated in high-resolution physiological time series data, thus an important gap is identified in previous studies that ignored the effects of HR and BR when measuring MV. We build a best-in-class open-source toolbox for exploring MV that accounts for the confounding factors of HR and BR. We demonstrate the toolbox’s utility in three domains on three different signals: arterial BP in sepsis; photoplethysmogram in coarctation of the aorta; and electrocardiogram (ECG) in post-traumatic stress disorder (PTSD). In each of the three case studies, incorporating features that capture MV while controlling for BR and/or HR improved disease classification performance compared to previously established methods that used features from lower resolution time series data. Using the PTSD example, we then introduce a deep learning approach that significantly improves our ability to identify the effects of PTSD on ECG morphology. In particular, we show that pre-training the algorithm on a database of over 70,000 ECGs containing a set of 25 rhythms, allowed us to boost performance from an area under the receiver operating characteristic curve (AUROC) of 0.61 to 0.85. This novel approach to identifying morphology indicates that there is much more to morphological variability during stressful PTSD-related events than the simple periodic modulation of the T-wave amplitude. This research indicates that future work should focus on identifying the etiology of the dynamic features in the ECG that provided such a large boost in performance, since this may reveal novel underlying mechanisms of the influence of PTSD on the myocardium.Ph.D

Intelligent monitoring and interpretation of preterm physiological signals using machine learning

Every year, more than one in ten babies are born prematurely. In Ireland of the 70000 babies delivered every year, 4500 are born too early. Premature babies are at a higher risk of complications, which may lead to both short-term and long-term adverse health outcomes. The neonatal population is especially vulnerable and a delay in the identification of medical conditions, as well as delays in the initiating the correct treatment, may be fatal. After birth, preterms are admitted to the neonatal intensive care unit (NICU), where a continuous flow of information in the form of physiological signals is available. Physiological signals can assist clinicians in decision making related to the diagnosis and treatment of various diseases. This information, however, can be highly complex, and usually requires expert analysis which may not be available at all times. The work conducted in this thesis develops a decision support systems for the intelligent monitoring of preterms in the NICU. This will allow for an accurate estimation of the current health status of the preterm neonate as well as the prediction of possible long-term complications. This thesis is comprised of three main work packages (WP), each addressing health complication of preterm on three different stages of life. At the first 12 hours of life the health status is quantified using the clinical risk index for babies (CRIB). This is followed by the assessment of the preterm’s well-being at discharge from the NICU using the clinical course score (CCS). Finally, the long-term neurodevelopmental follow-up is assessed using the Bayley III scales of development at two years. This is schematically represented in Figure 1 along with the main findings and contributions. Low blood pressure (BP) or hypotension is a recognised problem in preterm infants particularly during the first 72 hours of life. Hypotension may cause decreased cerebral perfusion, resulting in deprived oxygen delivery to the brain. Deciding when and whether to treat hypotension relies on our understanding of the relation between BP, oxygenation and brain activity. The electroencephalogram (EEG) is the most commonly used technology to assess the ‘brain health’ of a newborn. The first WP investigates the relationship between short-term dynamics in BP and EEG energy in the preterm on a large dataset of continuous multi-channel unedited EEG recordings in the context of the health status measured by the CRIB score. The obtained results indicate that a higher risk of mortality for the preterm is associated with a lower level of nonlinear interaction between EEG and BP. The level of coupling between these two systems can potentially serve as an additional source of information when deciding whether or not to intervene in the preterm. The electrocardiogram (ECG) is also routinely recorded in preterm infants. Analysis of heart rate variability (HRV) provides a non-invasive assessment of both the sympathetic and parasympathetic control of the heart rate. A novel automated objective decision support tool for the prediction of the short-term outcome (CCS) in preterm neonates who may have low BP is proposed in the second WP. Combining multiple HRV features extracted during hypotensive episodes, the classifier achieved an AUC of 0.97 for the task of short-term outcome prediction, using a leave-one-patient-out performance assessment. The developed system is based on the boosted decision tree classifier and allows for the continuous monitoring of the preterm. The proposed system is validated on a large clinically collected dataset of multimodal recordings from preterm neonates. If the correct treatment is initiated promptly after diagnosis, it can potentially improve the neurodevelopmental outcome of the preterm infant. The third WP presents a pilot study investigating the predictive capability of the early EEG recorded at discharge from the NICU with respect to the 2-year neurodevelopmental outcome using machine learning techniques. Two methods are used: 1) classical feature-based classifier, and 2) end-to-end deep learning. This is a fundamental study in this area, especially in the context of applying end-to-end learning to the preterm EEG for the problem of long-term outcome prediction. It is shown that for the available labelled dataset of 37 preterm neonates, the classical feature-based approach outperformed the end-to-end deep learning technique. A discussion of the obtained result as well as a section highlighting the possible limitations and areas that need to be investigated in the future are provided

A method to detect and represent temporal patterns from time series data and its application for analysis of physiological data streams

In critical care, complex systems and sensors continuously monitor patients??? physiological features such as heart rate, respiratory rate thus generating significant amounts of data every second. This results to more than 2 million records generated per patient in an hour. It???s an immense challenge for anyone trying to utilize this data when making critical decisions about patient care. Temporal abstraction and data mining are two research fields that have tried to synthesize time oriented data to detect hidden relationships that may exist in the data. Various researchers have looked at techniques for generating abstractions from clinical data. However, the variety and speed of data streams generated often overwhelms current systems which are not designed to handle such data. Other attempts have been to understand the complexity in time series data utilizing mining techniques, however, existing models are not designed to detect temporal relationships that might exist in time series data (Inibhunu & McGregor, 2016). To address this challenge, this thesis has proposed a method that extends the existing knowledge discovery frameworks to include components for detecting and representing temporal relationships in time series data. The developed method is instantiated within the knowledge discovery component of Artemis, a cloud based platform for processing physiological data streams. This is a unique approach that utilizes pattern recognition principles to facilitate functions for; (a) temporal representation of time series data with abstractions, (b) temporal pattern generation and quantification (c) frequent patterns identification and (d) building a classification system. This method is applied to a neonatal intensive care case study with a motivating problem that discovery of specific patterns from patient data could be crucial for making improved decisions within patient care. Another application is in chronic care to detect temporal relationships in ambulatory patient data before occurrence of an adverse event. The research premise is that discovery of hidden relationships and patterns in data would be valuable in building a classification system that automatically characterize physiological data streams. Such characterization could aid in detection of new normal and abnormal behaviors in patients who may have life threatening conditions

Advanced analyses of physiological signals and their role in Neonatal Intensive Care

Preterm infants admitted to the neonatal intensive care unit (NICU) face an array of life-threatening diseases requiring procedures such as resuscitation and invasive monitoring, and other risks related to exposure to the hospital environment, all of which may have lifelong implications. This thesis examined a range of applications for advanced signal analyses in the NICU, from identifying of physiological patterns associated with neonatal outcomes, to evaluating the impact of certain treatments on physiological variability. Firstly, the thesis examined the potential to identify infants at risk of developing intraventricular haemorrhage, often interrelated with factors leading to preterm birth, mechanical ventilation, hypoxia and prolonged apnoeas. This thesis then characterised the cardiovascular impact of caffeine therapy which is often administered to prevent and treat apnoea of prematurity, finding greater pulse pressure variability and enhanced responsiveness of the autonomic nervous system. Cerebral autoregulation maintains cerebral blood flow despite fluctuations in arterial blood pressure and is an important consideration for preterm infants who are especially vulnerable to brain injury. Using various time and frequency domain correlation techniques, the thesis found acute changes in cerebral autoregulation of preterm infants following caffeine therapy. Nutrition in early life may also affect neurodevelopment and morbidity in later life. This thesis developed models for identifying malnutrition risk using anthropometry and near-infrared interactance features. This thesis has presented a range of ways in which advanced analyses including time series analysis, feature selection and model development can be applied to neonatal intensive care. There is a clear role for such analyses in early detection of clinical outcomes, characterising the effects of relevant treatments or pathologies and identifying infants at risk of later morbidity

Camera-Based Remote Photoplethysmography for Estimation of Heart Rate using Single Board Computers

The objective of this project was to develop a wireless, noncontact monitoring system that measures multiple physiological parameters in human faces from a distance using a camera. Compared to traditional sensors, this monitoring system does not use wires or adhesives, providing a safer, more user-friendly application. The goal of the monitoring systems was to estimate heart rate (HR). The current practices of measuring HR involve collecting electrocardiogram (ECG) signals from adhesive electrodes placed on various parts of the body and using a pulse oximeter (PO) typically placed on the ear lobe or finger. We were able to successfully create 2 monitoring systems and compare their results to the PO. Both monitoring systems are low-cost at less than $200. Neither system has been shown to exist in literature thus making them novel implementations. After analysis, we found the estimated HR from one of the systems to be not significantly different from the PO readings. In conclusion, we were able to estimate HR from a distance using a camera-based system which can have many useful applications, potentially in the Neonatal ICU and in other home health settings

Use of Multiscale Entropy to Characterize Fetal Autonomic Development

The idea that uterine environment and adverse events during fetal development could increase the chances of the diseases in adulthood was first published by David Barker in 1998. Since then, investigators have been employing several methods and methodologies for studying and characterizing the ontological development of the fetus, e.g., fetal movement, growth and cardiac metrics. Even with most recent and developed methods such as fetal magnetocardiography (fMCG), investigators are continuously challenged to study fetal development; the fetus is inaccessible. Finding metrics that realize the full capacity of characterizing fetal ontological development remains a technological challenge. In this thesis, the use and value of multiscale entropy to characterize fetal maturation across third trimester of gestation is studied. Using multiscale entropy obtained from participants of a clinical trial, we show that MSE can characterize increasing complexity due to maturation in the fetus, and can distinguish a growing and developing fetal system from a mature system where loss of irregularity is due to compromised complexity from increasing physiologic load. MSE scales add a nonlinear metric that seems to accurately reflect the ontological development of the fetus and hold promise for future use to investigate the effects of maternal stress, intrauterine growth restriction, or predict risk for sudden infant death syndrome

Intelligent Biosignal Processing in Wearable and Implantable Sensors

This reprint provides a collection of papers illustrating the state-of-the-art of smart processing of data coming from wearable, implantable or portable sensors. Each paper presents the design, databases used, methodological background, obtained results, and their interpretation for biomedical applications. Revealing examples are brain–machine interfaces for medical rehabilitation, the evaluation of sympathetic nerve activity, a novel automated diagnostic tool based on ECG data to diagnose COVID-19, machine learning-based hypertension risk assessment by means of photoplethysmography and electrocardiography signals, Parkinsonian gait assessment using machine learning tools, thorough analysis of compressive sensing of ECG signals, development of a nanotechnology application for decoding vagus-nerve activity, detection of liver dysfunction using a wearable electronic nose system, prosthetic hand control using surface electromyography, epileptic seizure detection using a CNN, and premature ventricular contraction detection using deep metric learning. Thus, this reprint presents significant clinical applications as well as valuable new research issues, providing current illustrations of this new field of research by addressing the promises, challenges, and hurdles associated with the synergy of biosignal processing and AI through 16 different pertinent studies. Covering a wide range of research and application areas, this book is an excellent resource for researchers, physicians, academics, and PhD or master students working on (bio)signal and image processing, AI, biomaterials, biomechanics, and biotechnology with applications in medicine

The role of the vagus nerve during fetal development and its relationship with the environment

The autonomic nervous system (ANS) regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. Several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors (i.e. fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure) may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses.Comment: Word count: 16,009 Tables: 1 Figures: