Detecting Bulbar Involvement in Patients with Amyotrophic Lateral Sclerosis Based on Phonatory and Time-Frequency Features

The term bulbar involvement is employed in ALS to refer to deterioration of motor neurons within the corticobulbar area of the brainstem, which results in speech and swallowing dysfunctions. One of the primary symptoms is a deterioration of the voice. Early detection is crucial for improving the quality of life and lifespan of ALS patients suffering from bulbar involvement. The main objective, and the principal contribution, of this research, was to design a new methodology, based on the phonatory-subsystem and time-frequency characteristics for detecting bulbar involvement automatically. This study focused on providing a set of 50 phonatory-subsystem and time-frequency features to detect this deficiency in males and females through the utterance of the five Spanish vowels. Multivariant Analysis of Variance was then used to select the statistically significant features, and the most common supervised classifications models were analyzed. A set of statistically significant features was obtained for males and females to capture this dysfunction. To date, the accuracy obtained (98.01% for females and 96.10% for males employing a random forest) outperformed the models in the literature. Adding time-frequency features to more classical phonatory-subsystem features increases the prediction capabilities of the machine-learning models for detecting bulbar involvement. Studying men and women separately gives greater success. The proposed method can be deployed in any kind of recording device (i.e., smartphone)

Linear and complex measures of heart rate variability during exposure to traffic noise in healthy women

Previous studies have described significant impact of different types of noise on the linear behavior of heart rate variability (HRV). However, there are few studies regarding the complexity of HRV during exposure to traffic noise. In this study, we evaluated the complexity of HRV during traffic noise exposure. We analyzed 31 healthy female students aged between 18 and 30 years. Volunteers remained at rest seated under spontaneous breathing during 10 minutes with an earphone turned off, and then they were exposed to traffic noise through an earphone for a period of 10 minutes. The traffic noise was recorded from a very busy city street and the sound was comprised of car, bus, and trucks engines and horn (71-104 dB). We observed no significant changes in the linear analysis of HRV. CFP3 (Cohen's d = 1.28, large effect size) and CFP6 (Cohen's d = 1.11, large effect size) parameters of chaotic global analysis and Shannon (Cohen's d = 1.13, large effect size), Renyi (Cohen's d = 1.06, large effect size), and Tsallis (Cohen's d = 1.14, large effect size) entropies significantly increased (p < 0.005) during traffic noise exposure. In conclusion, traffic noise under laboratory conditions increased the complexity of HRV through chaotic global analysis and some measures of entropy in healthy females

Development of nonlinear techniques based on time-frequency representation and information theory for the analysis of EEG signals to assess different states of consciousness

Electroencephalogram (EEG) recordings provide insight into the changes in brain activity associated with various states of anesthesia, epilepsy, brain attentiveness, sleep disorders, brain disorders, etc. EEG's are complex signals whose statistical properties depend on both space and time. Their randomness and non-stationary characteristics make them impossible to be described in an accurate way with a simple technique, requiring analysis and characterization involves techniques that take into account their non-stationarity. For that, new advanced techniques in order to improve the efficiency of the EEG based methods used in the clinical practice have to be developed. The main objective of this thesis was to investigate and implement different methods based on nonlinear techniques in order to develop indexes able to characterize the frequency spectrum, the nonlinear dynamics and the complexity of the EEG signals recorded in different state of consciousness. Firstly, a new method for removing peak and spike in biological signal based on the signal envelope was successfully designed and applied to simulated and real EEG signals, obtaining performances significantly better than the traditional adaptive filters. Then, several studies were carried out in order to extract and evaluate EEG measures based on nonlinear techniques in different contexts such as the automatic detection of sleepiness and the characterization and prediction of the nociceptive stimuli and the assessment of the sedation level. Four novel indexes were defined by calculating entropy of the Choi-Williams distribution (CWD) with respect to time or frequency, by using the probability mass function at each time instant taken independently or by using the probability mass function of the entire CWD. The values of these indexes tend to decrease, with different proportion, when the behavior of the signals evolved from chaos or randomness to periodicity and present differences when comparing EEG recorded in eyes-open and eyes-closed states and in ictal and non-ictal states. Measures obtained with time-frequency representation, mutual information function and correntropy, were applied to EEG signals for the automatic sleepiness detection in patients suffering sleep disorders. The group of patients with excessive daytime sleepiness presented more power in ¿ band than the group without sleepiness, which presented higher spectral and cross-spectral entropy in the frontal zone in d band. More complexity in the occipital zone was found in the group of patients without sleepiness in ß band, while a stronger nonlinear coupling between the occipital and frontal regions was detected in patients with excessive daytime sleepiness, in ß band. Time-frequency representation and non-linear measures were also used in order to study how adaptation and fatigue affect the event-related brain potentials to stimuli of different modalities. Differences between the responses to infrequent and frequent stimulation in different recording periods were found in series of averaged EEG epochs recorded after thermal, electrical and auditory stimulation. Nonlinear measures calculated on EEG filtered in the traditional frequency bands and in higher frequency bands improved the assessment of the sedation level. These measures were obtained by applying all the developed techniques on signals recorded from patients sedated, in order to predict the responses to pain stimulation such as nail bad compression and endoscopy tube insertion. The proposed measures exhibit better performances than the bispectral index (BIS), a traditional indexes used for hypnosis assessment. In conclusion, nonlinear measures based on time-frequency representation, mutual information functions and correntropy provided additional information that helped to improve the automatic sleepiness detection, the characterization and prediction of the nociceptive responses and thus the assessment of the sedation level.El registro de la señal Electroencefalografíca (EEG) proporciona información sobre los cambios en la actividad cerebral asociados con varios estados de la anestesia, la epilepsia, la atención cerebral, los trastornos del sueño, los trastornos cerebrales, etc. Los EEG son señales complejas cuyas propiedades estadísticas dependen del espacio y del tiempo. Sus características aleatorias y no estacionarias hacen imposible que el EEG se describa de forma precisa con una técnica sencilla requiriendo un análisis y una caracterización que implica técnicas que tengan en cuenta su no estacionariedad. Todo esto aumenta la necesidad de desarrollar nuevas técnicas avanzadas con el fin de mejorar la eficiencia de los métodos utilizados en la práctica clínica que son basados en el análisis de EEG. En esta tesis se han investigado y aplicado diferentes métodos utilizando técnicas no lineales con el fin de desarrollar índices capaces de caracterizar el espectro de frecuencias, la dinámica no lineal y la complejidad de las señales EEG registradas en diferentes estados de conciencia. En primer lugar, se ha desarrollado un nuevo algoritmo basado en la envolvente de la señal para la eliminación de ruido de picos en las señales biológicas. Este algoritmo ha sido aplicado a señales simuladas y reales obteniendo resultados significativamente mejores comparados con los filtros adaptativos tradicionales. Seguidamente, se han llevado a cabo varios estudios con el fin de extraer y evaluar las medidas de EEG basadas en técnicas no lineales en diferentes contextos. Se han definido nuevos índices mediante el cálculo de la entropía de la distribución de Choi-Williams (DCW) con respecto al tiempo o la frecuencia. Se ha observado que los valores de estos índices tienden a disminuir, en diferentes proporciones, cuando el comportamiento de las señales evoluciona de caótico o aleatorio a periódico. Además, se han encontrado valores diferentes de estos índices aplicados a la señal EEG registrada en diferentes estados. Diferentes medidas basadas en la representación tiempo-frecuencia, la función de información mutua y la correntropia se han aplicado al EEG para la detección automática de la somnolencia en pacientes que sufren trastornos del sueño. Se ha observado en la zona frontal que la potencia en la banda θ es mayor en los pacientes con somnolencia diurna excesiva, mientras que la entropía espectral y la entropía espectral cruzada en la banda δ es mayor en los pacientes sin somnolencia. En el grupo sin somnolencia se ha encontrado más complejidad en la zona occipital, mientras que el acoplamiento no lineal entre las regiones occipital y frontal ha resultado más fuerte en pacientes con somnolencia diurna excesiva, en la banda β. La representación tiempo-frecuencia y las medidas no lineales se han utilizado para estudiar cómo la adaptación y la fatiga afectan a los potenciales cerebrales relacionados con estímulos térmicos, eléctricos y auditivos. Analizando el promedio de varias épocas de EEG grabadas después de la estimulación, se han encontrado diferencias entre las respuestas a la estimulación frecuente e infrecuente en diferentes períodos de registro. Todas las técnicas que se han desarrollado, se han aplicado a señales EEG registradas en pacientes sedados, con el fin de predecir las respuestas a la estimulación del dolor. Un conjunto de medidas calculadas en señales EEG filtradas en diferentes bandas de frecuencia ha permitido mejorar la evaluación del nivel de sedación. Las medidas propuestas han presentado un mejor rendimiento comparado con el índice bispectral, un indicador de hipnosis tradicional. En conclusión, las medidas no lineales basadas en la representación tiempofrecuencia, funciones de información mutua y correntropia han proporcionado informaciones adicionales que contribuyeron a mejorar la detección automática de la somnolencia, la caracterización y predicción de las respuestas nociceptivas y por lo tanto la evaluación del nivel de sedación

CEPS: An Open Access MATLAB Graphical User Interface (GUI) for the Analysis of Complexity and Entropy in Physiological Signals

Background: We developed CEPS as an open access MATLAB® GUI (graphical user interface) for the analysis of Complexity and Entropy in Physiological Signals (CEPS), and demonstrate its use with an example data set that shows the effects of paced breathing (PB) on variability of heart, pulse and respiration rates. CEPS is also sufficiently adaptable to be used for other time series physiological data such as EEG (electroencephalography), postural sway or temperature measurements. Methods: Data were collected from a convenience sample of nine healthy adults in a pilot for a larger study investigating the effects on vagal tone of breathing paced at various different rates, part of a development programme for a home training stress reduction system. Results: The current version of CEPS focuses on those complexity and entropy measures that appear most frequently in the literature, together with some recently introduced entropy measures which may have advantages over those that are more established. Ten methods of estimating data complexity are currently included, and some 28 entropy measures. The GUI also includes a section for data pre-processing and standard ancillary methods to enable parameter estimation of embedding dimension m and time delay τ (‘tau’) where required. The software is freely available under version 3 of the GNU Lesser General Public License (LGPLv3) for non-commercial users. CEPS can be downloaded at https://bitbucket.org/deepak_panday/ceps/src/pipeline_v2/. In our illustration on PB, most complexity and entropy measures decreased significantly in response to breathing at 7 breaths per minute, differentiating more clearly than conventional linear, time- and frequency-domain measures between breathing states. In contrast, Higuchi fractal dimension increased during paced breathing. Conclusions: We have developed CEPS software as a physiological data visualiser able to integrate state of the art techniques. The interface is designed for clinical research and has a structure designed for integrating new tools. The aim is to strengthen collaboration between clinicians and the biomedical community, as demonstrated here by using CEPS to analyse various physiological responses to paced breathing

Time-frequency features for impedance cardiography signals during anesthesia using different distribution kernels

Objective: This works investigates the time-frequency content of impedance cardiography signals during a propofol-remifentanil anesthesia. Materials and Methods: In the last years, impedance cardiography (ICG) is a technique which has gained much attention. However, ICG signals need further investigation. Time-Frequency Distributions (TFDs) with 5 different kernels are used in order to analyze impedance cardiography signals (ICG) before the start of the anesthesia and after the loss of consciousness. In total, ICG signals from one hundred and thirty-one consecutive patients undergoing major surgery under general anesthesia were analyzed. Several features were extracted from the calculated TFDs in order to characterize the time-frequency content of the ICG signals. Differences between those features before and after the loss of consciousness were studied. Results: The Extended Modified Beta Distribution (EMBD) was the kernel for which most features shows statistically significant changes between before and after the loss of consciousness. Among all analyzed features, those based on entropy showed a sensibility, specificity and area under the curve of the receiver operating characteristic above 60%. Conclusion: The anesthetic state of the patient is reflected on linear and non-linear features extracted from the TFDs of the ICG signals. Especially, the EMBD is a suitable kernel for the analysis of ICG signals and offers a great range of features which change according to the patient’s anesthesia state in a statistically significant way.Peer ReviewedPostprint (author's final draft

Automatic analysis and classification of cardiac acoustic signals for long term monitoring

Objective: Cardiovascular diseases are the leading cause of death worldwide resulting in over 17.9 million deaths each year. Most of these diseases are preventable and treatable, but their progression and outcomes are significantly more positive with early-stage diagnosis and proper disease management. Among the approaches available to assist with the task of early-stage diagnosis and management of cardiac conditions, automatic analysis of auscultatory recordings is one of the most promising ones, since it could be particularly suitable for ambulatory/wearable monitoring. Thus, proper investigation of abnormalities present in cardiac acoustic signals can provide vital clinical information to assist long term monitoring. Cardiac acoustic signals, however, are very susceptible to noise and artifacts, and their characteristics vary largely with the recording conditions which makes the analysis challenging. Additionally, there are challenges in the steps used for automatic analysis and classification of cardiac acoustic signals. Broadly, these steps are the segmentation, feature extraction and subsequent classification of recorded signals using selected features. This thesis presents approaches using novel features with the aim to assist the automatic early-stage detection of cardiovascular diseases with improved performance, using cardiac acoustic signals collected in real-world conditions. Methods: Cardiac auscultatory recordings were studied to identify potential features to help in the classification of recordings from subjects with and without cardiac diseases. The diseases considered in this study for the identification of the symptoms and characteristics are the valvular heart diseases due to stenosis and regurgitation, atrial fibrillation, and splitting of fundamental heart sounds leading to additional lub/dub sounds in the systole or diastole interval of a cardiac cycle. The localisation of cardiac sounds of interest was performed using an adaptive wavelet-based filtering in combination with the Shannon energy envelope and prior information of fundamental heart sounds. This is a prerequisite step for the feature extraction and subsequent classification of recordings, leading to a more precise diagnosis. Localised segments of S1 and S2 sounds, and artifacts, were used to extract a set of perceptual and statistical features using wavelet transform, homomorphic filtering, Hilbert transform and mel-scale filtering, which were then fed to train an ensemble classifier to interpret S1 and S2 sounds. Once sound peaks of interest were identified, features extracted from these peaks, together with the features used for the identification of S1 and S2 sounds, were used to develop an algorithm to classify recorded signals. Overall, 99 features were extracted and statistically analysed using neighborhood component analysis (NCA) to identify the features which showed the greatest ability in classifying recordings. Selected features were then fed to train an ensemble classifier to classify abnormal recordings, and hyperparameters were optimized to evaluate the performance of the trained classifier. Thus, a machine learning-based approach for the automatic identification and classification of S1 and S2, and normal and abnormal recordings, in real-world noisy recordings using a novel feature set is presented. The validity of the proposed algorithm was tested using acoustic signals recorded in real-world, non-controlled environments at four auscultation sites (aortic valve, tricuspid valve, mitral valve, and pulmonary valve), from the subjects with and without cardiac diseases; together with recordings from the three large public databases. The performance metrics of the methodology in relation to classification accuracy (CA), sensitivity (SE), precision (P+), and F1 score, were evaluated. Results: This thesis proposes four different algorithms to automatically classify fundamental heart sounds – S1 and S2; normal fundamental sounds and abnormal additional lub/dub sounds recordings; normal and abnormal recordings; and recordings with heart valve disorders, namely the mitral stenosis (MS), mitral regurgitation (MR), mitral valve prolapse (MVP), aortic stenosis (AS) and murmurs, using cardiac acoustic signals. The results obtained from these algorithms were as follows: • The algorithm to classify S1 and S2 sounds achieved an average SE of 91.59% and 89.78%, and F1 score of 90.65% and 89.42%, in classifying S1 and S2, respectively. 87 features were extracted and statistically studied to identify the top 14 features which showed the best capabilities in classifying S1 and S2, and artifacts. The analysis showed that the most relevant features were those extracted using Maximum Overlap Discrete Wavelet Transform (MODWT) and Hilbert transform. • The algorithm to classify normal fundamental heart sounds and abnormal additional lub/dub sounds in the systole or diastole intervals of a cardiac cycle, achieved an average SE of 89.15%, P+ of 89.71%, F1 of 89.41%, and CA of 95.11% using the test dataset from the PASCAL database. The top 10 features that achieved the highest weights in classifying these recordings were also identified. • Normal and abnormal classification of recordings using the proposed algorithm achieved a mean CA of 94.172%, and SE of 92.38%, in classifying recordings from the different databases. Among the top 10 acoustic features identified, the deterministic energy of the sound peaks of interest and the instantaneous frequency extracted using the Hilbert Huang-transform, achieved the highest weights. • The machine learning-based approach proposed to classify recordings of heart valve disorders (AS, MS, MR, and MVP) achieved an average CA of 98.26% and SE of 95.83%. 99 acoustic features were extracted and their abilities to differentiate these abnormalities were examined using weights obtained from the neighborhood component analysis (NCA). The top 10 features which showed the greatest abilities in classifying these abnormalities using recordings from the different databases were also identified. The achieved results demonstrate the ability of the algorithms to automatically identify and classify cardiac sounds. This work provides the basis for measurements of many useful clinical attributes of cardiac acoustic signals and can potentially help in monitoring the overall cardiac health for longer duration. The work presented in this thesis is the first-of-its-kind to validate the results using both, normal and pathological cardiac acoustic signals, recorded for a long continuous duration of 5 minutes at four different auscultation sites in non-controlled real-world conditions.Open Acces

Fusion of heart rate variability and salivary cortisol for stress response identification based on adverse childhood experience

Adverse childhood experiences have been suggested to cause changes in physiological processes and can determine the magnitude of the stress response which might have a significant impact on health later in life. To detect the stress response, biomarkers that represent both the Autonomic Nervous System (ANS) and Hypothalamic-Pituitary-Adrenal (HPA) axis are proposed. Among the available biomarkers, Heart Rate Variability (HRV) has been proven as a powerful biomarker that represents ANS. Meanwhile, salivary cortisol has been suggested as a biomarker that reflects the HPA axis. Even though many studies used multiple biomarkers to measure the stress response, the results for each biomarker were analyzed separately. Therefore, the objective of this study is to propose a fusion of ANS and HPA axis biomarkers in order to classify the stress response based on adverse childhood experience. Electrocardiograph, blood pressure (BP), pulse rate (PR), and salivary cortisol (SCort) measures were collected from 23 healthy participants; 11 participants had adverse childhood experience while the remaining 12 acted as the no adversity control group. HRV was then computed from the ECG and the HRV features were extracted. Next, the selected HRV features were combined with the other biomarkers using Euclidean distance (ed) and serial fusion, and the performance of the fused features was compared using Support Vector Machine. From the result, HRV-SCort using Euclidean distance achieved the most satisfactory performance with 80.0% accuracy, 83.3% sensitivity, and 78.3% specificity. Furthermore, the performance of the stress response classification of the fused biomarker, HRV-SCort, outperformed that of the single biomarkers: HRV (61% Accuracy), Cort (59.4% Accuracy), BP (78.3% accuracy), and PR (53.3% accuracy). From this study, it was proven that the fused biomarkers that represent both ANS and HPA (HRV-SCort) able to demonstrate a better classification performance in discriminating the stress response. Furthermore, a new approach for classification of stress response using Euclidean distance and SVM named as ed-SVM was proven to be an effective method for the HRV-SCort in classifying the stress response from PASAT. The robustness of this method is crucial in contributing to the effectiveness of the stress response measures and could further be used as an indicator for future health

Exploring the combined use of electrical and hemodynamic brain activity to investigate brain function

This thesis explored the relationship between electrical and metabolic aspects of brain functioning in health and disease, measured with QEEG and NIRS, in order to evaluate its clinical potential. First the limitations of NIRS were investigated, depicting its susceptibility to different types of motion artefacts and the inability of the CBSI-method to remove them from resting state data. Furthermore, the quality of the NIRS signals was poor in a significant portion of the investigated sample, reducing clinical potential. Different analysis methods were used to explore both EEG and NIRS, and their coupling in an eyes open eyes closed paradigm in healthy participants. It could be reproduced that during eyes closed blocks less HbO2 (p = 0.000), more Hbb (p = 0.008), and more alpha activity (p = 0.000) was present compared to eyes open blocks. Furthermore, dynamic cross correlation analysis reproduced a positive correlation between alpha and Hbb (r: 0.457 and 0.337) and a negative correlation between alpha and HbO2 (r: -0.380 and -0.366) with a delayed hemodynamic response (7 to 8s). This was only possible when removing all questionable and physiological illogical data, suggesting that an 8s hemodynamic delay might not be the golden standard. Also the inability of the cross correlation to take non-linear relationships into account may distort outcomes. Therefore, In chapter 5 non-linear aspects of the relationship were evaluated by introducing the measure of relative cross mutual information. A newly suggested approach and the most valuable contribution of the thesis since it broadens knowledge in the fields of EEG, NIRS and general time series analysis. Data of two stroke patients then showed differences from the healthy group between the coupling of EEG and NIRS. The differences in long range temporal correlations (p= 0.000 for both cases), entropy (p< 0.040 and p =0.000), and relative cross mutual information (p < 0.003 and p < 0.013) provide the proof of principle that these measures may have clinical utility. Even though more research is necessary before widespread clinical use becomes possible

Spectral Analysis for Signal Detection and Classification : Reducing Variance and Extracting Features

Spectral analysis encompasses several powerful signal processing methods. The papers in this thesis present methods for finding good spectral representations, and methods both for stationary and non-stationary signals are considered. Stationary methods can be used for real-time evaluation, analysing shorter segments of an incoming signal, while non-stationary methods can be used to analyse the instantaneous frequencies of fully recorded signals. All the presented methods aim to produce spectral representations that have high resolution and are easy to interpret. Such representations allow for detection of individual signal components in multi-component signals, as well as separation of close signal components. This makes feature extraction in the spectral representation possible, relevant features include the frequency or instantaneous frequency of components, the number of components in the signal, and the time duration of the components. Two methods that extract some of these features automatically for two types of signals are presented in this thesis. One adapted to signals with two longer duration frequency modulated components that detects the instantaneous frequencies and cross-terms in the Wigner-Ville distribution, the other for signals with an unknown number of short duration oscillations that detects the instantaneous frequencies in a reassigned spectrogram. This thesis also presents two multitaper methods that reduce the influence of noise on the spectral representations. One is designed for stationary signals and the other for non-stationary signals with multiple short duration oscillations. Applications for the methods presented in this thesis include several within medicine, e.g. diagnosis from analysis of heart rate variability, improved ultrasound resolution, and interpretation of brain activity from the electroencephalogram

Advanced bioimpedance signal processing techniques for hemodynamic monitoring during anesthesia

Cardiac output (CO) defines the blood flow arriving from the heart to the different organs in the body and it is thus a primary determinant of global 02 transport. Cardiac output has traditionally been measured using invasive methods, whose risk sometimes exceeds the advantages of a cardiac output monitoring. In this context, the minimization of risk in new noninvasive technologies for CO monitoring could translate into major advantages for clinicians, hospitals and patients: ease of usage and availability, reduced recovery time, and improved patient outcome. Impedance Cardiography (ICG) is a promising noninvasive technology for cardiac output monitoring but available information on the ICG signals is more scare than other physiological signals such as the electrocardiogram (ECG). The present Doctoral Thesis contributes to the development of signal treatment techniques for the ICG in order to create an innovative hemodynamic monitor. First, an extensive literature review is provided regarding the basics of the clinical background in which cardiac output monitoring is used and concerning the state of the art of cardiac output monitors on the market. This Doctoral Thesis has produced a considerable amount of clinical data which is also explained in detail. These clinical data are also useful to complement the theoretical explanation of patient indices such as heart rate variability, blood flow and blood pressure. In addition, a new method to create synthetic biomedical signals with known time-frequency characteristics is introduced. One of the first analysis in this Doctoral Thesis studies the time difference between peak points of the heart beats in the ECG and the ICG: the RC segment. This RC segment is a measure of the time delay between electrical and mechanical activity of the heart. The relationship of the RC segment with blood pressure and heart interval is analyzed. The concordance of beat durations of both the electrocardiogram and the impedance cardiogram is one of the key results to develop new artefact detection algorithms and the RC could also have an impact in describing the hemodynamics of a patient. Time-frequency distributions (TFDs) are also used to characterize how the frequency content in impedance cardiography signals change with time. Since TFDs are calculated using concrete kernels, a new method to select the best kernel by using synthetic signals is presented. Optimized TFDs of ICG signals are then calculated to extract severa! features which are used to discriminate between different anesthesia states in patients undergoing surgery. TFD-derived features are also used to describe the whole surgical operations. Relationships between TFD-derived features are analyzed and prediction models for cardiac output are designed. These prediction models prove that the TFD-derived features are related to the patients' cardiac output. Finally, a validation study for the qCO monitor is presented. The qCO monitor has been designed using sorne of the techniques which are consequence of this Doctoral Thesis. The main outputs of this work have been protected with a patent which has already been filed. As a conclusion, this Doctoral Thesis has produced a considerable amount of clinical data and a variety of analysis and processing techniques of impedance cardiography signals which have been included into commercial medical devices already available on the market.El gasto cardíaco (GC) define el flujo de sangre que llega desde el corazón a los distintos órganos del cuerpo y es, por tanto, un determinante primario del transporte global de oxígeno. Se ha medido tradicionalmente usando métodos invasivos cuyos riesgos excedían en ocasiones las ventajas de su monitorización. En este contexto, la minimización del riesgo de la monitorización del gasto cardíaco en nuevas tecnologías no invasivas podría traducirse en mayores ventajas para médicos, hospitales y pacientes: facilidad de uso, disponibilidad del equipamiento y menor tiempo de recuperación y mejores resultados en el paciente. La impedancio-cardiografía o cardiografía de impedancia (ICG} es una prometedora tecnología no invasiva para la monitorización del gasto cardíaco. Sin embargo, la información disponible sobre las señales de ICG es más escasa que otras señales fisiológicas como el electrocardiograma (ECG). La presente Tesis Doctoral contribuye al desarrollo de técnicas de tratamiento de señal de ICG para así crear un monitor hemodinámico innovador. En primer lugar, se proporciona una extensa revisión bibliográfica sobre los aspectos básicos del contexto clínico en el que se utiliza la monitorización del gasto cardíaco así como sobre el estado del arte de los monitores de gasto cardíaco que existen en el mercado. Esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos que también se explican en detalle. Dichos datos clínicos también son útiles para complementar las explicaciones teóricas de los índices de paciente de variabilidad cardíaca y el flujo y la presión sanguíneos. Además, se presenta un nuevo método de creación de señales sintéticas biomédicas con características de tiempo-frecuencia conocidas. Uno de los primeros análisis de esta Tesis Doctoral estudia la diferencia temporal entre los picos de los latidos cardíacos del ECG y del ICG: el segmento RC. Este segmento RC es una medida del retardo temporal entre la actividad eléctrica y mecánica del corazón. Se analiza la relación del segmento RC con la presión arterial y el intervalo cardíaco. La concordancia entre la duración de los latidos del ECG y del ICG es uno de los resultados claves para desarrollar nuevos algoritmos de detección de artefactos y el segmento RC también podría ser relevante en la descripción de la hemodinámica de los pacientes. Las distribuciones de tiempo-frecuencia (TFD, por sus siglas en inglés) se utilizan para caracterizar cómo el contenido de las señales de impedancia cardiográfica cambia con el tiempo. Dado que las TFDs deben calcularse usando núcleos (kernels, en inglés) concretos, se presenta un nuevo método para seleccionar el mejor núcleo mediante el uso de señales sintéticas. Las TFDs de ICG optimizadas se calculan para extraer distintas características que son usadas para discriminar entre los diferentes estados de anestesia en pacientes sometidos a procesos quirúrgicos. Las características derivadas de las distribuciones de tiempo-frecuencia también son utilizadas para describir las operaciones quirúrgicas durante toda su extensión temporal. La relación entre dichas características son analizadas y se proponen distintos modelos de predicción para el gasto cardíaco. Estos modelos de predicción demuestran que las características derivadas de las distribuciones tiempo-frecuencia de señales de ICG están relacionadas con el gasto cardíaco de los pacientes. Finalmente, se presenta un estudio de validación del monitor qCO, diseñado con alguna de las técnicas que son consecuencia de esta Tesis Doctoral. Las principales conclusiones de este trabajo han sido protegidas con una patente que ya ha sido registrada. Como conclusión, esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos y una variedad de técnicas de procesado y análisis de señales de cardiografía de impedancia que han sido incluidas en dispositivos biomédicos disponibles en el mercad