The non-invasive fetal ECG (NIFECG), derived from abdominal surface electrodes, offers novel diagnostic possibilities for prenatal medicine. Despite its straightforward applicability, NIFECG signals are usually corrupted by many interfering sources. Most significantly, by the maternal ECG (MECG), whose amplitude usually exceeds that of the fetal ECG (FECG) by multiple times. The presence of additional noise sources (e.g. muscular/uterine noise, electrode motion, etc.) further affects the signal-to-noise ratio (SNR) of the FECG. These interfering sources, which typically show a strong non-stationary behavior, render the FECG extraction and fetal QRS (FQRS) detection demanding signal processing tasks. In this thesis, several of the challenges regarding NIFECG signal analysis were addressed. In order to improve NIFECG extraction, the dynamic model of a Kalman filter approach was extended, thus, providing a more adequate representation of the mixture of FECG, MECG, and noise. In addition, aiming at the FECG signal quality assessment, novel metrics were proposed and evaluated. Further, these quality metrics were applied in improving FQRS detection and fetal heart rate estimation based on an innovative evolutionary algorithm and Kalman filtering signal fusion, respectively. The elaborated methods were characterized in depth using both simulated and clinical data, produced throughout this thesis. To stress-test extraction algorithms under ideal circumstances, a comprehensive benchmark protocol was created and contributed to an extensively improved NIFECG simulation toolbox. The developed toolbox and a large simulated dataset were released under an open-source license, allowing researchers to compare results in a reproducible manner. Furthermore, to validate the developed approaches under more realistic and challenging situations, a clinical trial was performed in collaboration with the University Hospital of Leipzig. Aside from serving as a test set for the developed algorithms, the clinical trial enabled an exploratory research. This enables a better understanding about the pathophysiological variables and measurement setup configurations that lead to changes in the abdominal signal's SNR. With such broad scope, this dissertation addresses many of the current aspects of NIFECG analysis and provides future suggestions to establish NIFECG in clinical settings.

The non-invasive fetal ECG (NIFECG), derived from abdominal surface electrodes, offers novel diagnostic possibilities for prenatal medicine. Despite its straightforward applicability, NIFECG signals are usually corrupted by many interfering sources. Most significantly, by the maternal ECG (MECG), whose amplitude usually exceeds that of the fetal ECG (FECG) by multiple times. The presence of additional noise sources (e.g. muscular/uterine noise, electrode motion, etc.) further affects the signal-to-noise ratio (SNR) of the FECG. These interfering sources, which typically show a strong non-stationary behavior, render the FECG extraction and fetal QRS (FQRS) detection demanding signal processing tasks. In this thesis, several of the challenges regarding NIFECG signal analysis were addressed. In order to improve NIFECG extraction, the dynamic model of a Kalman filter approach was extended, thus, providing a more adequate representation of the mixture of FECG, MECG, and noise. In addition, aiming at the FECG signal quality assessment, novel metrics were proposed and evaluated. Further, these quality metrics were applied in improving FQRS detection and fetal heart rate estimation based on an innovative evolutionary algorithm and Kalman filtering signal fusion, respectively. The elaborated methods were characterized in depth using both simulated and clinical data, produced throughout this thesis. To stress-test extraction algorithms under ideal circumstances, a comprehensive benchmark protocol was created and contributed to an extensively improved NIFECG simulation toolbox. The developed toolbox and a large simulated dataset were released under an open-source license, allowing researchers to compare results in a reproducible manner. Furthermore, to validate the developed approaches under more realistic and challenging situations, a clinical trial was performed in collaboration with the University Hospital of Leipzig. Aside from serving as a test set for the developed algorithms, the clinical trial enabled an exploratory research. This enables a better understanding about the pathophysiological variables and measurement setup configurations that lead to changes in the abdominal signal's SNR. With such broad scope, this dissertation addresses many of the current aspects of NIFECG analysis and provides future suggestions to establish NIFECG in clinical settings.:Abstract Acknowledgment Contents List of Figures List of Tables List of Abbreviations List of Symbols (1)Introduction 1.1)Background and Motivation 1.2)Aim of this Work 1.3)Dissertation Outline 1.4)Collaborators and Conflicts of Interest (2)Clinical Background 2.1)Physiology 2.1.1)Changes in the maternal circulatory system 2.1.2)Intrauterine structures and feto-maternal connection 2.1.3)Fetal growth and presentation 2.1.4)Fetal circulatory system 2.1.5)Fetal autonomic nervous system 2.1.6)Fetal heart activity and underlying factors 2.2)Pathology 2.2.1)Premature rupture of membrane 2.2.2)Intrauterine growth restriction 2.2.3)Fetal anemia 2.3)Interpretation of Fetal Heart Activity 2.3.1)Summary of clinical studies on FHR/FHRV 2.3.2)Summary of studies on heart conduction 2.4)Chapter Summary (3)Technical State of the Art 3.1)Prenatal Diagnostic and Measuring Technique 3.1.1)Fetal heart monitoring 3.1.2)Related metrics 3.2)Non-Invasive Fetal ECG Acquisition 3.2.1)Overview 3.2.2)Commercial equipment 3.2.3)Electrode configurations 3.2.4)Available NIFECG databases 3.2.5)Validity and usability of the non-invasive fetal ECG 3.3)Non-Invasive Fetal ECG Extraction Methods 3.3.1)Overview on the non-invasive fetal ECG extraction methods 3.3.2)Kalman filtering basics 3.3.3)Nonlinear Kalman filtering 3.3.4)Extended Kalman filter for FECG estimation 3.4)Fetal QRS Detection 3.4.1)Merging multichannel fetal QRS detections 3.4.2)Detection performance 3.5)Fetal Heart Rate Estimation 3.5.1)Preprocessing the fetal heart rate 3.5.2)Fetal heart rate statistics 3.6)Fetal ECG Morphological Analysis 3.7)Problem Description 3.8)Chapter Summary (4)Novel Approaches for Fetal ECG Analysis 4.1)Preliminary Considerations 4.2)Fetal ECG Extraction by means of Kalman Filtering 4.2.1)Optimized Gaussian approximation 4.2.2)Time-varying covariance matrices 4.2.3)Extended Kalman filter with unknown inputs 4.2.4)Filter calibration 4.3)Accurate Fetal QRS and Heart Rate Detection 4.3.1)Multichannel evolutionary QRS correction 4.3.2)Multichannel fetal heart rate estimation using Kalman filters 4.4)Chapter Summary (5)Data Material 5.1)Simulated Data 5.1.1)The FECG Synthetic Generator (FECGSYN) 5.1.2)The FECG Synthetic Database (FECGSYNDB) 5.2)Clinical Data 5.2.1)Clinical NIFECG recording 5.2.2)Scope and limitations of this study 5.2.3)Data annotation: signal quality and fetal amplitude 5.2.4)Data annotation: fetal QRS annotation 5.3)Chapter Summary (6)Results for Data Analysis 6.1)Simulated Data 6.1.1)Fetal QRS detection 6.1.2)Morphological analysis 6.2)Own Clinical Data 6.2.1)FQRS correction using the evolutionary algorithm 6.2.2)FHR correction by means of Kalman filtering (7)Discussion and Prospective 7.1)Data Availability 7.1.1)New measurement protocol 7.2)Signal Quality 7.3)Extraction Methods 7.4)FQRS and FHR Correction Algorithms (8)Conclusion References (A)Appendix A - Signal Quality Annotation (B)Appendix B - Fetal QRS Annotation (C)Appendix C - Data Recording GUI