Electrocardiogram: Acquisition and Analysis for Biological Investigations and Health Monitoring

Electrocardiogram (ECG or EKG) was introduced since 1893 by Einthoven, and it has been used for decades in clinical settings for vital sign monitoring as well as cardiac assessment. The ECG signal with its unique characteristic waves of P waves, QRS complexes, and T waves holds important information about the functionalities of the heart. In recent years, advances in electronics and telecommunications have paved the way for out-of-clinic ECG acquisition and monitoring. The rise of advanced data science techniques, such as machine learning, has further opened doors for distanced, home-based, and automated diagnoses. In parallel, micro- and nanotechnology has enabled significant strides in biological investigations using small animal models, such as zebrafish and mouse, uncovering underlying mechanisms of numerous biological processes. In this chapter, we first introduce the basics of electrocardiogram and the methods for acquisition; and then systems used with zebrafish and humans are discussed. Artificial intelligence, specifically machine learning, is brought into the discussion with an emphasis on the use of convolutional neuron networks for classifying ECG patterns of arrhythmic zebrafish mutants. Finally, the chapter recapitulates with the necessity of translating findings from animal research for use with humans as well as a body sensor network with multimodal sensors which may reveal unprecedented connections among physiological parameters.

[1]  D. S. Luciano,et al.  Human Physiology: The Mechanism of Body Function , 1975 .

[2]  Hung Cao,et al.  An Implantable, Batteryless, and Wireless Capsule With Integrated Impedance and pH Sensors for Gastroesophageal Reflux Monitoring , 2012, IEEE Transactions on Biomedical Engineering.

[3]  S. Ekker,et al.  A modifier screen identifies DNAJB6 as a cardiomyopathy susceptibility gene. , 2016, JCI insight.

[4]  Daeyoung Kim,et al.  Premature Ventricular Contraction Beat Detection with Deep Neural Networks , 2016, 2016 15th IEEE International Conference on Machine Learning and Applications (ICMLA).

[5]  P. Ellinor,et al.  Next-generation sequencing for the diagnosis of cardiac arrhythmia syndromes. , 2015, Heart rhythm.

[6]  Z. Obermeyer,et al.  Predicting the Future - Big Data, Machine Learning, and Clinical Medicine. , 2016, The New England journal of medicine.

[7]  Tanya M. Teslovich,et al.  Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development. , 2018, American journal of human genetics.

[8]  Hung Cao,et al.  A novel design to power the micro-ECG sensor implanted in adult zebrafish , 2017, 2017 IEEE International Symposium on Antennas and Propagation & USNC/URSI National Radio Science Meeting.

[9]  Stephen C. Ekker,et al.  in vivo protein trapping produces a functional expression codex of the vertebrate proteome , 2011, Nature Methods.

[10]  Jonathan M. Brunger,et al.  CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation‐Resistant Tissues , 2017, Arthritis & rheumatology.

[11]  Peter Norvig,et al.  The Unreasonable Effectiveness of Data , 2009, IEEE Intelligent Systems.

[12]  Ashutosh Gupta,et al.  Neural Network based indicative ECG classification , 2014, 2014 5th International Conference - Confluence The Next Generation Information Technology Summit (Confluence).

[13]  P. Visscher,et al.  10 Years of GWAS Discovery: Biology, Function, and Translation. , 2017, American journal of human genetics.

[14]  Amay J Bandodkar,et al.  Non-invasive wearable electrochemical sensors: a review. , 2014, Trends in biotechnology.

[15]  Hung Cao,et al.  Wireless Passive Monitoring of Electrocardiogram in Firefighters , 2018, 2018 IEEE International Microwave Biomedical Conference (IMBioC).

[16]  C. Lien,et al.  Micro-Electrocardiograms to Study Post-Ventricular Amputation of Zebrafish Heart , 2009, Annals of Biomedical Engineering.

[17]  Y. Zhang,et al.  A wearable mobihealth care system supporting real-time diagnosis and alarm , 2007, Medical & Biological Engineering & Computing.

[18]  Qiang Yang,et al.  A Survey on Transfer Learning , 2010, IEEE Transactions on Knowledge and Data Engineering.

[19]  Fei Yu,et al.  Evolving cardiac conduction phenotypes in developing zebrafish larvae: implications to drug sensitivity. , 2010, Zebrafish.

[20]  Aurélien Géron,et al.  Hands-On Machine Learning with Scikit-Learn and TensorFlow: Concepts, Tools, and Techniques to Build Intelligent Systems , 2017 .

[21]  Su Guo,et al.  Use of zebrafish as a model to understand mechanisms of addiction and complex neurobehavioral phenotypes , 2010, Neurobiology of Disease.

[22]  Tzyy-Ping Jung,et al.  Dry-Contact and Noncontact Biopotential Electrodes: Methodological Review , 2010, IEEE Reviews in Biomedical Engineering.

[23]  M. Herráez,et al.  Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure. , 2015, Environmental pollution.

[24]  Bor-Shyh Lin,et al.  Development of Novel Non-Contact Electrodes for Mobile Electrocardiogram Monitoring System , 2013, IEEE Journal of Translational Engineering in Health and Medicine.

[25]  Akbar K Waljee,et al.  Machine Learning in Medicine: A Primer for Physicians , 2010, The American Journal of Gastroenterology.

[26]  Ryan M. Anderson,et al.  Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes , 2010, Nature.

[27]  C. Lien,et al.  Heart repair and regeneration: Recent insights from zebrafish studies , 2012, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[28]  Hung Cao,et al.  Wireless power transfer for ECG monitoring in freely-swimming zebrafish , 2017, 2017 IEEE SENSORS.

[29]  Gert Cauwenberghs,et al.  Ultra-High Input Impedance, Low Noise Integrated Amplifier for Noncontact Biopotential Sensing , 2011, IEEE Journal on Emerging and Selected Topics in Circuits and Systems.

[30]  Chin-Teng Lin,et al.  Design, Fabrication and Experimental Validation of a Novel Dry-Contact Sensor for Measuring Electroencephalography Signals without Skin Preparation , 2011, Sensors.

[31]  Laure Bally-Cuif,et al.  The zebrafish as a model system for assessing the reinforcing properties of drugs of abuse. , 2006, Methods.

[32]  Kevin Bersell,et al.  Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury , 2009, Cell.

[33]  D. M. Ribeiro,et al.  A Novel Dry Active Biosignal Electrode Based on an Hybrid Organic-Inorganic Interface Material , 2011, IEEE Sensors Journal.

[34]  S. Ekker,et al.  Trapping Cardiac Recessive Mutants via Expression-Based Insertional Mutagenesis Screening , 2013, Circulation research.

[35]  Samuel Bernard,et al.  Evidence for Cardiomyocyte Renewal in Humans , 2008, Science.

[36]  Hung Cao,et al.  Real-Time Monitoring and Analysis of Zebrafish Electrocardiogram with Anomaly Detection , 2017, Sensors.

[37]  Hung Cao,et al.  Unobtrusive acquisition and extraction of fetal and maternal ECG in the home setting , 2017, 2017 IEEE SENSORS.

[38]  Tai Le,et al.  A low cost mobile ECG monitoring device using two active dry electrodes , 2016, 2016 IEEE Sixth International Conference on Communications and Electronics (ICCE).

[39]  Roberto Merletti,et al.  Technology and instrumentation for detection and conditioning of the surface electromyographic signal: state of the art. , 2009, Clinical biomechanics.

[40]  R. Klabunde,et al.  Comprar Cardiovascular Physiology Concepts | Richard E. Klabunde | 9781451113846 | Lippincott Williams & Wilkins , 2011 .

[41]  K. Borgwardt,et al.  Machine Learning in Medicine , 2015, Mach. Learn. under Resour. Constraints Vol. 3.

[42]  Yong-Gyu Lee,et al.  Smartphone-based mobile health monitoring. , 2012, Telemedicine journal and e-health : the official journal of the American Telemedicine Association.

[43]  Yu-Te Wang,et al.  Development of a Wearable Mobile Electrocardiogram Monitoring System by Using Novel Dry Foam Electrodes , 2014, IEEE Systems Journal.

[44]  M. Keating,et al.  Heart Regeneration in Zebrafish , 2002, Science.

[45]  Jari Hyttinen,et al.  Effect of pressure and padding on motion artifact of textile electrodes , 2013, Biomedical engineering online.

[46]  Daniel St Johnston,et al.  The art and design of genetic screens: Drosophila melanogaster , 2002, Nature Reviews Genetics.

[47]  Skylar W. Marvel,et al.  Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish , 2017, Toxicology and applied pharmacology.

[48]  C. Macrae,et al.  Animal models for arrhythmias. , 2005, Cardiovascular research.

[49]  Emil Jovanov,et al.  APPLICATIONS OF SMARTPHONES FOR UBIQUITOUS HEALTH MONITORING AND WELLBEING MANAGEMENT , 2011 .

[50]  Thomas Lavergne,et al.  Sudden cardiac arrest associated with early repolarization. , 2008, The New England journal of medicine.

[51]  M. Gharib,et al.  Electrocardiographic Characterization of Embryonic Zebrafish , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[52]  W. Pu,et al.  Cardiac Regeneration , 2017, Cardiac and Vascular Biology.

[53]  Kathleen F. Kerr,et al.  Fifteen Genetic Loci Associated With the Electrocardiographic P Wave , 2017, Circulation. Cardiovascular genetics.

[54]  A. Gruetzmann,et al.  Novel dry electrodes for ECG monitoring , 2007, Physiological measurement.

[55]  Jianhong Yang,et al.  Dry electrode for the measurement of biopotential signals , 2011, Science China Information Sciences.

[56]  L. Piwek,et al.  The Rise of Consumer Health Wearables: Promises and Barriers , 2016, PLoS medicine.

[57]  Mohamed Adel Serhani,et al.  Novel Cloud and SOA-Based Framework for E-Health Monitoring Using Wireless Biosensors , 2014, IEEE Journal of Biomedical and Health Informatics.

[58]  Jeffrey Robbins,et al.  Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury , 2007, Nature Medicine.

[59]  Xiong Yu,et al.  Capacitive Biopotential Measurement for Electrophysiological Signal Acquisition: A Review , 2016, IEEE Sensors Journal.

[60]  H. Firth,et al.  Fetal cardiac anomalies and genetic syndromes , 2004, Prenatal diagnosis.

[61]  Jeffrey E. Thatcher,et al.  C/EBP Transcription Factors Mediate Epicardial Activation During Heart Development and Injury , 2012, Science.

[62]  Sergey Ioffe,et al.  Rethinking the Inception Architecture for Computer Vision , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[63]  Tzung K Hsiai,et al.  Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts , 2012, Biomedical microdevices.

[64]  David P. Nusinow,et al.  Networked-based characterization of extracellular matrix proteins from adult mouse pulmonary and aortic valves. , 2011, Journal of proteome research.

[65]  Hung Cao,et al.  Characterization of Passive Wireless Electrocardiogram Acquisition in Adult Zebrafish , 2018, 2018 IEEE International Microwave Biomedical Conference (IMBioC).

[66]  Erik M. Jorgensen,et al.  The art and design of genetic screens: Caenorhabditis elegans , 2002, Nature Reviews Genetics.

[67]  R. Virmani,et al.  Apoptosis in myocytes in end-stage heart failure. , 1996, The New England journal of medicine.

[68]  C A Beltrami,et al.  Apoptosis in the failing human heart. , 1997, The New England journal of medicine.

[69]  S. Forsburg The art and design of genetic screens: yeast , 2001, Nature Reviews Genetics.

[70]  A. Consiglio,et al.  The zebrafish as a model of heart regeneration. , 2004, Cloning and stem cells.

[71]  G. Cauwenberghs,et al.  Micropower non-contact EEG electrode with active common-mode noise suppression and input capacitance cancellation , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[72]  Fei Yu,et al.  Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium. , 2014, Integrative biology : quantitative biosciences from nano to macro.

[73]  M. Ackerman,et al.  Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise , 2013, Current opinion in cardiology.

[74]  Tzung K. Hsiai,et al.  Cuff-Less and Continuous Blood Pressure Monitoring: A Methodological Review , 2017 .

[75]  E. Olson,et al.  Transient Regenerative Potential of the Neonatal Mouse Heart , 2011, Science.

[76]  L. Edmonds,et al.  Prevalence of birth defects among infants of Gulf War veterans in Arkansas, Arizona, California, Georgia, Hawaii, and Iowa, 1989-1993. , 2003, Birth defects research. Part A, Clinical and molecular teratology.

[77]  J. Dimarco,et al.  Use of ambulatory electrocardiographic (Holter) monitoring. , 1990, Annals of internal medicine.

[78]  Hung Cao,et al.  Design and development of continuous cuff-less blood pressure monitoring devices , 2016, 2016 IEEE SENSORS.

[79]  Daniel Sánchez Morillo,et al.  Dry EEG Electrodes , 2014, Sensors.

[80]  Li Zhang,et al.  An efficient abnormal beat detection scheme from ECG signals using neural network and ensemble classifiers , 2014, The 8th International Conference on Software, Knowledge, Information Management and Applications (SKIMA 2014).