Estrazione non invasiva del segnale elettrocardiografico fetale da registrazioni con elettrodi posti sull’addome della gestante (Non-invasive extraction of the fetal electrocardiogram from abdominal recordings by positioning electrodes on the pregnant woman’s abdomen)

openIl cuore è il primo organo che si sviluppa nel feto, particolarmente nelle primissime settimane di gestazione. Rispetto al cuore adulto, quello fetale ha una fisiologia ed un’anatomia significativamente differenti, a causa della differente circolazione cardiovascolare. Il benessere fetale si valuta monitorando l’attività cardiaca mediante elettrocardiografia fetale (ECGf). L’ECGf invasivo (acquisito posizionando elettrodi allo scalpo fetale) è considerato il gold standard, ma l’invasività che lo caratterizza ne limita la sua applicabilità. Al contrario, l’uso clinico dell’ECGf non invasivo (acquisito posizionando elettrodi sull’addome della gestante) è limitato dalla scarsa qualità del segnale risultante. L’ECGf non invasivo si estrae da registrazioni addominali, che sono corrotte da differenti tipi di rumore, fra i quali l’interferenza primaria è rappresentata dall’ECG materno. Il Segmented-Beat Modulation Method (SBMM) è stato da me recentemente proposto come una nuova procedura di filtraggio basata sul calcolo del template del battito cardiaco. SBMM fornisce una stima ripulita dell’ECG estratto da registrazioni rumorose, preservando la fisiologica variabilità ECG del segnale originale. Questa caratteristica è ottenuta grazie alla segmentazione di ogni battito cardiaco per indentificare i segmenti QRS e TUP, seguito dal processo di modulazione/demodulazione (che include strecciamento e compressione) del segmento TUP, per aggiustarlo in modo adattativo alla morfologia e alla durata di ogni battito originario. Dapprima applicato all’ECG adulto al fine di dimostrare la sua robustezza al rumore, l’SBMM è stato poi applicato al caso fetale. Particolarmente significativi sono i risultati relativi alle applicazioni su ECGf non invasivo, dove l’SBMM fornisce segnali caratterizzati da un rapporto segnale-rumore comparabile a quello caratterizzante l’ECGf invasivo. Tuttavia, l’SBMM può contribuire alla diffusione dell’ECGf non invasiva nella pratica clinica.The heart is the first organ that develops in the fetus, particularly in the very early stages of pregnancy. Compared to the adult heart, the physiology and anatomy of the fetal heart exhibit some significant differences. These differences originate from the fact that the fetal cardiovascular circulation is different from the adult circulation. Fetal well-being evaluation may be accomplished by monitoring cardiac activity through fetal electrocardiography (fECG). Invasive fECG (acquired through scalp electrodes) is the gold standard but its invasiveness limits its clinical applicability. Instead, clinical use of non-invasive fECG (acquired through abdominal electrodes) has so far been limited by its poor signal quality. Non-invasive fECG is extracted from the abdominal recording and is corrupted by different kind of noise, among which maternal ECG is the main interference. The Segmented-Beat Modulation Method (SBMM) was recently proposed by myself as a new template-based filtering procedure able to provide a clean ECG estimation from a noisy recording by preserving physiological ECG variability of the original signal. The former feature is achieved thanks to a segmentation procedure applied to each cardiac beat in order to identify the QRS and TUP segments, followed by a modulation/demodulation process (involving stretching and compression) of the TUP segments to adaptively adjust each estimated cardiac beat to the original beat morphology and duration. SBMM was first applied to adult ECG applications, in order to demonstrate its robustness to noise, and then to fECG applications. Particularly significant are the results relative to the non-invasive applications, where SBMM provided fECG signals characterized by a signal-to-noise ratio comparable to that characterizing invasive fECG. Thus, SBMM may contribute to the spread of this noninvasive fECG technique in the clinical practice.INGEGNERIA DELL'INFORMAZIONEAgostinelli, AngelaAgostinelli, Angel

Extraction and Detection of Fetal Electrocardiograms from Abdominal Recordings

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 GU

Advanced Signal Processing in Wearable Sensors for Health Monitoring

Smart, wearables devices on a miniature scale are becoming increasingly widely available, typically in the form of smart watches and other connected devices. Consequently, devices to assist in measurements such as electroencephalography (EEG), electrocardiogram (ECG), electromyography (EMG), blood pressure (BP), photoplethysmography (PPG), heart rhythm, respiration rate, apnoea, and motion detection are becoming more available, and play a significant role in healthcare monitoring. The industry is placing great emphasis on making these devices and technologies available on smart devices such as phones and watches. Such measurements are clinically and scientifically useful for real-time monitoring, long-term care, and diagnosis and therapeutic techniques. However, a pertaining issue is that recorded data are usually noisy, contain many artefacts, and are affected by external factors such as movements and physical conditions. In order to obtain accurate and meaningful indicators, the signal has to be processed and conditioned such that the measurements are accurate and free from noise and disturbances. In this context, many researchers have utilized recent technological advances in wearable sensors and signal processing to develop smart and accurate wearable devices for clinical applications. The processing and analysis of physiological signals is a key issue for these smart wearable devices. Consequently, ongoing work in this field of study includes research on filtration, quality checking, signal transformation and decomposition, feature extraction and, most recently, machine learning-based methods

Algorithms and systems for home telemonitoring in biomedical applications

During the past decades, the interest of the healthcare community shifted from the simple treatment of the diseases towards the prevention and maintenance of a healthy lifestyle. This approach is associated to a reduced cost for the Health Systems, having to face the constantly increased expenditures due to the reduced mortality for chronical diseases and to the progressive population ageing. Nevertheless, the high costs related to hospitalization of patients for monitoring procedures that could be better performed at home hamper the full implementation of this approach in a traditional way. Information and Communication Technology can provide a solution to implement a care model closer to the patient, crossing the physical boundaries of the hospitals and thus allowing to reach also those patients that, for a geographical or social condition, could not access the health services as other luckier subjects. This is the case of telemonitoring systems, whose aim is that of providing monitoring services for some health-related parameters at a distance, by means of custom-designed electronic devices. In this thesis, the specific issues associated to two telemonitoring applications are presented, along with the proposed solutions and the achieved results. The first telemonitoring application considered is the fetal electrocardiography. Non-invasive fetal electrocardiography is the recording of the fetal heart electrical activity using electrodes placed on the maternal abdomen. It can provide important diagnostic parameters, such as the beat-to-beat heart rate variability, whose recurring analysis would be useful in assessing and monitoring fetal health during pregnancy. Long term electrocardiographic monitoring is sustained by the absence of any collateral effects for both the mother and the fetus. This application has been tackled from several perspectives, mainly acquisition and processing. From the acquisition viewpoint a study on different skin treatments, disposable commercial electrodes and textile electrodes has been performed with the aim of improving the signal acquisition quality, while simplifying the measurement setup. From the processing viewpoint, different algorithms have been developed to allow extracting the fetal ECG heart rate, starting from an on-line ICA algorithm or exploiting a subtractive approach to work on recordings acquired with a reduced number of electrodes. The latter, took part to the international "Physionet/Computing in Cardiology Challenge" in 2013 entering into the top ten best-performing open-source algorithms. The improved version of this algorithm is also presented, which would mark the 5th and 4th position in the final ranking related to the fetal heart rate and fetal RR interval measurements performance, reserved to the open-source challenge entries, taking into account both official and unofficial entrants. The research in this field has been carried out in collaboration with the Pediatric Cardiology Unit of the Hospital G. Brotzu in Cagliari, for the acquisition of non-invasive fetal ECG signals from pregnant voluntary patients. The second telemonitoring application considered is the telerehabilitation of the hand. The execution of rehabilitation exercises has been proven to be effective in recovering hand functionality in a wide variety of invalidating diseases, but the lack of standardization and continuous medical control cause the patients neglecting this therapeutic procedures. Telemonitoring the rehabilitation sessions would allow the physician to closely follow the patients' progresses and compliance to the prescribed adapted exercises. This application leads to the development of a sensorized telerehabilitation system for the execution and objective monitoring of therapeutic exercises at the patients' home and of the telemedicine infrastructure that give the physician the opportunity to monitor patients' progresses through parameters summarizing the patients' performance. The proposed non-CE marked medical device, patent pending, underwent a clinical trial, reviewed and approved by the Italian Public Health Department, involving 20 patients with Rheumatoid Arthritis and 20 with Systemic Sclerosis randomly assigned to the experimental or the control arm, enrolled for 12 weeks in a home rehabilitation program. The trial, carried out with the collaboration of the Rheumatology Department of the Policlinico Universitario of Cagliari, revealed promising results in terms of hand functionality recovering, highlighting greater improvements for the patients enrolled in the experimental arm, that use the proposed telerehabilitation system, with respect to those of the control arm, which perform similar rehabilitation exercises using common objects

Recent Trends in Computational Research on Diseases

Recent advances in information technology have brought forth a paradigm shift in science, especially in the biology and medical fields. Statistical methodologies based on high-performance computing and big data analysis are now indispensable for the qualitative and quantitative understanding of experimental results. In fact, the last few decades have witnessed drastic improvements in high-throughput experiments in health science, for example, mass spectrometry, DNA microarray, next generation sequencing, etc. Those methods have been providing massive data involving four major branches of omics (genomics, transcriptomics, proteomics, and metabolomics). Information about amino acid sequences, protein structures, and molecular structures are fundamental data for the prediction of bioactivity of chemical compounds when screening drugs. On the other hand, cell imaging, clinical imaging, and personal healthcare devices are also providing important data concerning the human body and disease. In parallel, various methods of mathematical modelling such as machine learning have developed rapidly. All of these types of data can be utilized in computational approaches to understand disease mechanisms, diagnosis, prognosis, drug discovery, drug repositioning, disease biomarkers, driver mutations, copy number variations, disease pathways, and much more. In this Special Issue, we have published 8 excellent papers dedicated to a variety of computational problems in the biomedical field from the genomic level to the whole-person physiological level

Combining Synthesis of Cardiorespiratory Signals and Artifacts with Deep Learning for Robust Vital Sign Estimation

Healthcare has been remarkably morphing on the account of Big Data. As Machine Learning (ML) consolidates its place in simpler clinical chores, more complex Deep Learning (DL) algorithms have struggled to keep up, despite their superior capabilities. This is mainly attributed to the need for large amounts of data for training, which the scientific community is unable to satisfy. The number of promising DL algorithms is considerable, although solutions directly targeting the shortage of data lack. Currently, dynamical generative models are the best bet, but focus on single, classical modalities and tend to complicate significantly with the amount of physiological effects they can simulate. This thesis aims at providing and validating a framework, specifically addressing the data deficit in the scope of cardiorespiratory signals. Firstly, a multimodal statistical synthesizer was designed to generate large, annotated artificial signals. By expressing data through coefficients of pre-defined, fitted functions and describing their dependence with Gaussian copulas, inter- and intra-modality associations were learned. Thereafter, new coefficients are sampled to generate artificial, multimodal signals with the original physiological dynamics. Moreover, normal and pathological beats along with artifacts were included by employing Markov models. Secondly, a convolutional neural network (CNN) was conceived with a novel sensor-fusion architecture and trained with synthesized data under real-world experimental conditions to evaluate how its performance is affected. Both the synthesizer and the CNN not only performed at state of the art level but also innovated with multiple types of generated data and detection error improvements, respectively. Cardiorespiratory data augmentation corrected performance drops when not enough data is available, enhanced the CNN’s ability to perform on noisy signals and to carry out new tasks when introduced to, otherwise unavailable, types of data. Ultimately, the framework was successfully validated showing potential to leverage future DL research on Cardiology into clinical standards

Emotion and Stress Recognition Related Sensors and Machine Learning Technologies

This book includes impactful chapters which present scientific concepts, frameworks, architectures and ideas on sensing technologies and machine learning techniques. These are relevant in tackling the following challenges: (i) the field readiness and use of intrusive sensor systems and devices for capturing biosignals, including EEG sensor systems, ECG sensor systems and electrodermal activity sensor systems; (ii) the quality assessment and management of sensor data; (iii) data preprocessing, noise filtering and calibration concepts for biosignals; (iv) the field readiness and use of nonintrusive sensor technologies, including visual sensors, acoustic sensors, vibration sensors and piezoelectric sensors; (v) emotion recognition using mobile phones and smartwatches; (vi) body area sensor networks for emotion and stress studies; (vii) the use of experimental datasets in emotion recognition, including dataset generation principles and concepts, quality insurance and emotion elicitation material and concepts; (viii) machine learning techniques for robust emotion recognition, including graphical models, neural network methods, deep learning methods, statistical learning and multivariate empirical mode decomposition; (ix) subject-independent emotion and stress recognition concepts and systems, including facial expression-based systems, speech-based systems, EEG-based systems, ECG-based systems, electrodermal activity-based systems, multimodal recognition systems and sensor fusion concepts and (x) emotion and stress estimation and forecasting from a nonlinear dynamical system perspective

Conception de système de traitement de données sur les émotions d’un être humain dans un environnement mobile et incertain

Une émotion humaine est considérée comme un état d’esprit d’un individu qui est complexe et intense, débutant de manière brutale et peut durer pendant une période relativement brève. Les émotions affectent généralement à la fois l’état physiologique et psychologique et peuvent aider à améliorer la santé humaine et l’efficacité au travail si elles sont positives, tandis que les émotions négatives peuvent causer des problèmes de santé et de comportements très graves. La détection et la surveillance des émotions sont primordiales dans de nombreux domaines tels que la conduite de véhicules, afin d’agir dans le temps opportun en cas de présence d’un état émotionnel négatif qui peut affecter dangereusement la vie du conducteur. Dans la science, on a défini plusieurs méthodes de détection d’émotions qui peuvent être classifiées en deux grandes catégories ; l’une utilise les signaux physiques humains tels que l’expression faciale, la parole, le geste, la posture, etc., qui ont l’avantage d’être facilement collectés et étudiés, mais qui souffrent d’une fiabilité modeste en raison de la possibilité de ne pas montrer les signaux physiques vrais pour cacher de véritables émotions. La deuxième catégorie utilise les signaux internes (les signaux physiologiques), qui comprennent l’électrocardiogramme (ECG), l’électroencéphalogramme (EEG), la température (T), l’électromyogramme (EMG), etc. qui sont plus fiable due à leur nature interne et non contrôler directement par l’être humain. Dans cette thèse, nous avons étudié le problème de la détection des émotions humaines chez un conducteur de véhicule en se basant sur le signal ECG. Pour cela, nous avons proposé trois contributions liées à la détection des émotions. La première est une approche d’optimisation des paramètres de classification des catégories des signaux ECG qui parmi elle une classe ECG anormale représentant un état émotionnel inhabituel. La deuxième contribution est une version améliorée de l’approche Random Forest pour la dé- tection de l’état du stress d’un conducteur. La troisième contribution est un système de détection d’émotions en suggérant une approche d’apprentissage profond ; il s’agit d’un nouveau réseau de ivneurones convolutif et d’augmentation de données qui considère la variabilité de la fréquence cardiaque (Heart Rate Variability -HRV-) comme critère essentiel de détection. Le système proposé a été bien développé et prouvé par une étude de validation et une comparaison avec les travaux de référence similaires proposés dans la littérature

Recent Developments in Smart Healthcare

Medicine is undergoing a sector-wide transformation thanks to the advances in computing and networking technologies. Healthcare is changing from reactive and hospital-centered to preventive and personalized, from disease focused to well-being centered. In essence, the healthcare systems, as well as fundamental medicine research, are becoming smarter. We anticipate significant improvements in areas ranging from molecular genomics and proteomics to decision support for healthcare professionals through big data analytics, to support behavior changes through technology-enabled self-management, and social and motivational support. Furthermore, with smart technologies, healthcare delivery could also be made more efficient, higher quality, and lower cost. In this special issue, we received a total 45 submissions and accepted 19 outstanding papers that roughly span across several interesting topics on smart healthcare, including public health, health information technology (Health IT), and smart medicine