Fusing Continuous-valued Medical Labels using a Bayesian Model

With the rapid increase in volume of time series medical data available through wearable devices, there is a need to employ automated algorithms to label data. Examples of labels include interventions, changes in activity (e.g. sleep) and changes in physiology (e.g. arrhythmias). However, automated algorithms tend to be unreliable resulting in lower quality care. Expert annotations are scarce, expensive, and prone to significant inter- and intra-observer variance. To address these problems, a Bayesian Continuous-valued Label Aggregator(BCLA) is proposed to provide a reliable estimation of label aggregation while accurately infer the precision and bias of each algorithm. The BCLA was applied to QT interval (pro-arrhythmic indicator) estimation from the electrocardiogram using labels from the 2006 PhysioNet/Computing in Cardiology Challenge database. It was compared to the mean, median, and a previously proposed Expectation Maximization (EM) label aggregation approaches. While accurately predicting each labelling algorithm's bias and precision, the root-mean-square error of the BCLA was 11.78$\pm$0.63ms, significantly outperforming the best Challenge entry (15.37$\pm$2.13ms) as well as the EM, mean, and median voting strategies (14.76$\pm$0.52ms, 17.61$\pm$0.55ms, and 14.43$\pm$0.57ms respectively with $p<0.0001$)

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

When in doubt ask the crowd : leveraging collective intelligence for improving event detection and machine learning

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Variational Optimisation for Non-conjugate Likelihood Gaussian Process Models

In this thesis we address the problems associated to non-conjugate likelihood Gaussian process models, i.e., probabilistic models where the likelihood function and the Gaussian process priors are non-conjugate. Such problems include intractability, scalability, and poor local optima solutions for the parameters and hyper-parameters of the models. Particularly, in this thesis we address the aforementioned issues in the context of probabilistic models, where the likelihood’s parameters are modelled as latent parameter functions drawn from correlated Gaussian processes. We study three ways to generate such latent parameter functions: 1. from a linear model of coregionalisation; 2. from convolution processes, i.e., a convolution integral between smoothing kernels and Gaussian process priors; and 3. using variational inducing kernels, an alternative form to generate the latent parameter functions through the convolution processes formalism, by using a double convolution integral. We borrow ideas from different variational optimisation mechanisms, that consist on introducing a variational (or exploratory) distribution over the model so as to build objective functions that: allow us to deal with intractability as well as enabling scalability when needing to hand massive amounts of data observations. Also, such variational optimisations mechanisms grant us to perform inference of the model hyper-parameters together with the posterior’s parameters through a fully natural gradient optimisation scheme; a useful scheme for tackling the problem of poor local optima solutions. Such variational optimisation mechanisms have been broadly studied in the context of reinforcement and Bayesian deep learning showing to be successful exploratory-learning tools; nonetheless, they have not been much studied in the context of Gaussian process models, so we provide a study of their performance in said context

Computer modeling and signal analysis of cardiovascular physiology

This dissertation aims to study cardiovascular physiology from the cellular level to the whole heart level to the body level using numerical approaches. A mathematical model was developed to describe electromechanical interaction in the heart. The model integrates cardio-electrophysiology and cardiac mechanics through excitation-induced contraction and deformation-induced currents. A finite element based parallel simulation scheme was developed to investigate coupled electrical and mechanical functions. The developed model and numerical scheme were utilized to study cardiovascular dynamics at cellular, tissue and organ levels. The influence of ion channel blockade on cardiac alternans was investigated. It was found that the channel blocker may significantly change the critical pacing period corresponding to the onset of alternans as well as the alternans’ amplitude. The influence of electro-mechanical coupling on cardiac alternans was also investigated. The study supported the earlier assumptions that discordant alternans is induced by the interaction of conduction velocity and action potential duration restitution at high pacing rates. However, mechanical contraction may influence the spatial pattern and onset of discordant alternans. Computer algorithms were developed for analysis of human physiology. The 12-lead electrocardiography (ECG) is the gold standard for diagnosis of various cardiac abnormalities. However, disturbances and mistakes may modify physiological waves in ECG and lead to wrong diagnoses. This dissertation developed advanced signal analysis techniques and computer software to detect and suppress artifacts and errors in ECG. These algorithms can help to improve the quality of health care when integrated into medical devices or services. Moreover, computer algorithms were developed to predict patient mortality in intensive care units using various physiological measures. Models and analysis techniques developed here may help to improve the quality of health care

Quality control and cost management in crowdsourcing

By harvesting online workers’ knowledge, crowdsourcing has become an efficient and cost-effective way to obtain a large amount of labeled data for solving human intelligent tasks (HITs), such as entity resolution and sentiment analysis. Due to the open nature of crowdsourcing, online workers with different knowledge backgrounds may provide conflicting labels to tasks. Therefore, it is a common practice to perform a pre-determined number of assignments, either per task or for all tasks, and aggregate collected labels to infer the true label of tasks. This model could suffer from poor accuracy in case of under-budget or a waste of resource in case of over-budget. In addition, as worker labels are usually aggregated in a voting manner, crowdsourcing systems are vulnerable to strategic Sybil attack, where the attacker may manipulate several robot Sybil workers to share randomized labels for outvoting independent workers and apply various strategies to evade Sybil detection. In this thesis, we are specifically interested in providing a guaranteed aggregation accuracy with minimum worker cost and defending against strategic Sybil attack. In our first work, we assume that workers are independent and honest. By enforcing a specified accuracy threshold on aggregated labels and minimizing the worker cost under this requirement, we formulate the dual requirements for quality and cost as a Guaranteed Accuracy Problem (GAP) and present an efficient task assignment algorithm for solving the problem. In our second work, we assume that strategic Sybil attackers may coordinate Sybil workers to obtain rewards without honestly labeling tasks and apply different strategies to evade detection. By camouflaging golden tasks (i.e., tasks with known true labels) from the attacker and suppressing the impact of Sybil workers and low-quality independent workers, we extend the principled truth discovery to defend against strategic Sybil attack in crowdsorucing. For both works, we conduct comprehensive empirical evaluations on real and synthetic datasets to demonstrate the effectiveness and efficiency of our methods

The Application of Computer Techniques to ECG Interpretation

This book presents some of the latest available information on automated ECG analysis written by many of the leading researchers in the field. It contains a historical introduction, an outline of the latest international standards for signal processing and communications and then an exciting variety of studies on electrophysiological modelling, ECG Imaging, artificial intelligence applied to resting and ambulatory ECGs, body surface mapping, big data in ECG based prediction, enhanced reliability of patient monitoring, and atrial abnormalities on the ECG. It provides an extremely valuable contribution to the field

Probabilistic latent variable models for knowledge discovery and optimization

I conduct a systematic study of probabilistic latent variable models (PLVMs) with applications to knowledge discovery and optimization. Probabilistic modeling is a principled means to gain insight of data. By assuming that the observed data are generated from a distribution, we can estimate its density, or the statistics of our interest, by either Maximum Likelihood Estimation or Bayesian inference, depending on whether there is a prior distribution for the parameters of the assumed data distribution. One of the primary goals of various machine learning/data mining models is to reveal the underlying knowledge of observed data. A common practice is to introduce latent variables, which are modeled together with the observations. Such latent variables compute, for example, the class assignments (labels), the cluster membership, as well as other unobserved measurements of the data. Besides, proper exploitation of latent variables facilities the optimization itself, which leads to computationally efficient inference algorithms. In this thesis, I describe a range of applications where latent variables can be leveraged for knowledge discovery and efficient optimization. Works in this thesis demonstrate that PLVMs are a powerful tool for modeling incomplete observations. Through incorporating latent variables and assuming that the observations such as citations, pairwise preferences as well as text are generated following tractable distributions parametrized by the latent variables, PLVMs are flexible and effective to discover knowledge in data mining problems, where the knowledge is mathematically modelled as continuous or discrete values, distributions or uncertainty. In addition, I also explore PLVMs for deriving efficient algorithms. It has been shown that latent variables can be employed as a means for model reduction and facilitates the computation/sampling of intractable distributions. Our results lead to algorithms which take advantage of latent variables in probabilistic models. We conduct experiments against state-of-the-art models and empirical evaluation shows that our proposed approaches improve both learning performance and computational efficiency