Characterization and processing of novel neck photoplethysmography signals for cardiorespiratory monitoring

Epilepsy is a neurological disorder causing serious brain seizures that severely affect the patients' quality of life. Sudden unexpected death in epilepsy (SUDEP), for which no evident decease reason is found after post-mortem examination, is a common cause of mortality. The mechanisms leading to SUDEP are uncertain, but, centrally mediated apneic respiratory dysfunction, inducing dangerous hypoxemia, plays a key role. Continuous physiological monitoring appears as the only reliable solution for SUDEP prevention. However, current seizure-detection systems do not show enough sensitivity and present a high number of intolerable false alarms. A wearable system capable of measuring several physiological signals from the same body location, could efficiently overcome these limitations. In this framework, a neck wearable apnea detection device (WADD), sensing airflow through tracheal sounds, was designed. Despite the promising performance, it is still necessary to integrate an oximeter sensor into the system, to measure oxygen saturation in blood (SpO2) from neck photoplethysmography (PPG) signals, and hence, support the apnea detection decision. The neck is a novel PPG measurement site that has not yet been thoroughly explored, due to numerous challenges. This research work aims to characterize neck PPG signals, in order to fully exploit this alternative pulse oximetry location, for precise cardiorespiratory biomarkers monitoring. In this thesis, neck PPG signals were recorded, for the first time in literature, in a series of experiments under different artifacts and respiratory conditions. Morphological and spectral characteristics were analyzed in order to identify potential singularities of the signals. The most common neck PPG artifacts critically corrupting the signal quality, and other breathing states of interest, were thoroughly characterized in terms of the most discriminative features. An algorithm was further developed to differentiate artifacts from clean PPG signals. Both, the proposed characterization and classification model can be useful tools for researchers to denoise neck PPG signals and exploit them in a variety of clinical contexts. In addition to that, it was demonstrated that the neck also offered the possibility, unlike other body parts, to extract the Jugular Venous Pulse (JVP) non-invasively. Overall, the thesis showed how the neck could be an optimum location for multi-modal monitoring in the context of diseases affecting respiration, since it not only allows the sensing of airflow related signals, but also, the breathing frequency component of the PPG appeared more prominent than in the standard finger location. In this context, this property enabled the extraction of relevant features to develop a promising algorithm for apnea detection in near-real time. These findings could be of great importance for SUDEP prevention, facilitating the investigation of the mechanisms and risk factors associated to it, and ultimately reduce epilepsy mortality.Open Acces

Autonomic nervous system biomarkers from multi-modal and model-based signal processing in mental health and illness

Esta tesis se centra en técnicas de procesado multimodal y basado en modelos de señales para derivar parámetros fisiológicos, es decir, biomarcadores, relacionados con el sistema nervioso autónomo (ANS). El desarrollo de nuevos métodos para derivar biomarcadores de ANS no invasivos en la salud y la enfermedad mental ofrece la posibilidad de mejorar la evaluación del estrés y la monitorización de la depresión. Para este fin, el presente documento se estructura en tres partes principales. En la Parte I, se proporciona unaintroducción a la salud y la enfermedad mental (Cap. 1). Además, se presenta un marco teórico para investigar la etiología de los trastornos mentales y el papel del estrés en la enfermedad mental (Cap. 2). También se destaca la importancia de los biomarcadores no invasivos para la evaluación del ANS, prestando especial atención en la depresión clínica (Cap. 3, 4). En la Parte II, se proporciona el marco metodológico para derivar biomarcadores del ANS. Las técnicas de procesado de señales incluyen el análisis conjunto de la variabilidad del rítmo cardíaco (HRV) y la señal respiratoria (Cap. 6), técnicas novedosas para derivar la señal respiratoria del electrocardiograma (ECG) (Cap. 7) y un análisis robusto que se basa en modelar la forma de ondas del pulso del fotopletismograma (PPG) (Ch. 8). En la Parte III, los biomarcadores del ANS se evalúan en la quantificacióndel estrés (Cap. 9) y en la monitorización de la depresión (Ch. 10).Parte I: La salud mental no solo está relacionada con ese estado positivo de bienestar, en el que un individuo puede enfrentar a las situaciones estresantes de la vida, sino también con la ausencia de enfermedad mental. La enfermedad o trastorno mental se puede definir como un trastorno emocional, cognitivo o conductual que causa un deterioro funcional sustancial en una o más actividades importantes de la vida. Los trastornos mentales más comunes, que muchas veces coexisten, son la ansiedad y el trastorno depresivo mayor (MDD). La enfermedad mental tiene un impacto negativo en la calidad de vida, ya que se asocia con pérdidas considerables en la salud y el funcionamiento, y aumenta ignificativamente el riesgo de una persona de padecer enfermedades ardiovasculares.Un instigador común que subyace a la comorbilidad entre el MDD, la patologíacardiovascular y la ansiedad es el estrés mental. El estrés es común en nuestra vida de rítmo rapido e influye en nuestra salud mental. A corto plazo, ANS controla la respuesta cardiovascular a estímulos estresantes. La regulación de parámetros fisiológicos, como el rítmo cardíaco, la frecuencia respiratoria y la presión arterial, permite que el organismo responda a cambios repentinos en el entorno. Sin embargo, la adaptación fisiológica a un fenómeno ambiental que ocurre regularmente altera los sistemas biológicos involucrados en la respuesta al estrés. Las alteraciones neurobiológicas en el cerebro pueden alterar lafunción del ANS. La disfunción del ANS y los cambios cerebrales estructurales tienen un impacto negativo en los procesos cognitivos, emocionales y conductuales, lo que conduce al desarrollo de una enfermedad mental.Parte II: El desarrollo de métodos novedosos para derivar biomarcadores del ANS no invasivos ofrece la posibilidad de mejorar la evaluacón del estrés en individuos sanos y la disfunción del ANS en pacientes con MDD. El análisis conjunto de varias bioseñales (enfoquemultimodal) permite la cuantificación de interacciones entre sistemas biológicos asociados con ANS, mientras que el modelado de bioseãles y el análisis posterior de los parámetros del modelo (enfoque basado en modelos) permite la cuantificación robusta de cambios en mecanismos fisiológicos relacionados con el ANS. Un método novedoso, quetiene en cuenta los fenómenos de acoplo de fase y frecuencia entre la respiración y las señales de HRV para evaluar el acoplo cardiorrespiratorio no lineal cuadrático se propone en el Cap. 6.3. En el Cap. 7 se proponen nuevas técnicas paramejorar lamonitorización de la respiración. En el Cap. 8, para aumentar la robustez de algunas medidas morfológicas que reflejan cambios en el tonno arterial, se considera el modelado del pulso PPG como una onda principal superpuesta con varias ondas reflejadas.Parte III: Los biomarcadores del ANS se evalúan en la cuantificación de diferentes tipos de estrés, ya sea fisiológico o psicológico, en individuos sanos, y luego, en la monitorización de la depresión. En presencia de estrés mental (Cap. 9.1), inducido por tareas cognitivas, los sujetos sanos muestran un incremento en la frecuencia respiratoria y un mayor número de interacciones no lineales entre la respiración y la seãl de HRV. Esto podría estar asociado con una activación simpática, pero también con una respiración menos regular. En presencia de estrés hemodinámico (Cap. 9.2), inducido por un cambio postural, los sujetos sanos muestran una reducción en el acoplo cardiorrespiratoriono lineal cuadrático, que podría estar relacionado con una retracción vagal. En presencia de estrés térmico (Cap. 9.3), inducido por la exposición a emperaturas ambientales elevadas, los sujetos sanos muestran un aumento del equilibrio simpatovagal. Esto demuestra que los biomarcadores ANS son capaces de evaluar diferentes tipos de estrés y pueden explorarse más en el contexto de la monitorización de la depresión. En el Cap. 10, se evalúan las diferencias en la función del ANS entre elMDD y los sujetos sanos durante un protocolo de estrés mental, no solo con los valores brutos de los biomarcadores del ANS, sino también con los índices de reactividad autónoma, que reflejan la capacidad deun individuo para afrontar con una situación desafiante. Los resultados muestran que la depresión se asocia con un desequilibrio autonómico, que se caracteriza por una mayor actividad simpática y una reducción de la distensibilidad arterial. Los índices de reactividad autónoma cuantificados por cambios, entre etapas de estrés y de recuperación, en los sustitutos de la rigidez arterial, como la pérdida de amplitud de PPG en las ondas reflejadas, muestran el mejor rendimiento en términos de correlación con el grado de la depresión, con un coeficiente de correlación r = −0.5. La correlación negativa implicaque un mayor grado de depresión se asocia con una disminución de la reactividadautónoma. El poder discriminativo de los biomarcadores del ANS se aprecia también por su alto rendimiento diagnóstico para clasificar a los sujetos como MDD o sanos, con una precisión de 80.0%. Por lo tanto, se puede concluir que los biomarcadores del ANS pueden usarse para evaluar el estrés y que la distensibilidad arterial deteriorada podría constituir un biomarcador de salud mental útil en el seguimiento de la depresión.This dissertation is focused on multi-modal and model-based signal processing techniques for deriving physiological parameters, i.e. biomarkers, related to the autonomic nervous system (ANS). The development of novel approaches for deriving noninvasive ANS biomarkers in mental health and illness offers the possibility to improve the assessment of stress and the monitoring of depression. For this purpose, the present document is structured in three main parts. In Part I, an introduction to mental health and illness is provided (Ch. 1). Moreover, a theoretical framework for investigating the etiology of mental disorders and the role of stress in mental illness is presented (Ch. 2). The importance of noninvasive biomarkers for ANS assessment, paying particular attention in clinical depression, is also highlighted (Ch. 3, 4). In Part II, themethodological framework for deriving ANS biomarkers is provided. Signal processing techniques include the joint analysis of heart rate variability (HRV) and respiratory signals (Ch. 6), novel techniques for deriving the respiratory signal from electrocardiogram (ECG) (Ch. 7), and a robust photoplethysmogram(PPG)waveform analysis based on amodel-based approach (Ch. 8). In Part III, ANS biomarkers are evaluated in stress assessment (Ch. 9) and in the monitoring of depression (Ch. 10). Part I:Mental health is not only related to that positive state ofwell-being, inwhich an individual can cope with the normal stresses of life, but also to the absence of mental illness. Mental illness or disorder can be defined as an emotional, cognitive, or behavioural disturbance that causes substantial functional impairment in one or more major life activities. The most common mental disorders, which are often co-occurring, are anxiety and major depressive disorder (MDD). Mental illness has a negative impact on the quality of life, since it is associated with considerable losses in health and functioning, and increases significantly a person’s risk for cardiovascular diseases. A common instigator underlying the co-morbidity between MDD, cardiovascular pathology, and anxiety is mental stress. Stress is common in our fast-paced society and strongly influences our mental health. In the short term, ANS controls the cardiovascular response to stressful stimuli. Regulation of physiological parameters, such as heart rate, respiratory rate, and blood pressure, allows the organism to respond to sudden changes in the environment. However, physiological adaptation to a regularly occurring environmental phenomenon alters biological systems involved in stress response. Neurobiological alterations in the brain can disrupt the function of the ANS. ANS dysfunction and structural brain changes have a negative impact on cognitive, emotional, and behavioral processes, thereby leading to development of mental illness. Part II: The development of novel approaches for deriving noninvasive ANS biomarkers offers the possibility to improve the assessment of stress in healthy individuals and ANS dysfunction in MDD patients. Joint analysis of various biosignals (multi-modal approach) allows for the quantification of interactions among biological systems associated with ANS, while the modeling of biosignals and subsequent analysis of the model’s parameters (model-based approach) allows for the robust quantification of changes in physiological mechanisms related to the ANS. A novel method, which takes into account both phase and frequency locking phenomena between respiration and HRV signals, for assessing quadratic nonlinear cardiorespiratory coupling is proposed in Ch. 6.3. Novel techniques for improving the monitoring of respiration are proposed in Ch. 7. In Ch. 8, to increase the robustness for some morphological measurements reflecting arterial tone changes, the modeling of the PPG pulse as amain wave superposed with several reflected waves is considered. Part III: ANS biomarkers are evaluated in the assessment of different types of stress, either physiological or psychological, in healthy individuals, and then, in the monitoring of depression. In the presence of mental stress (Ch. 9.1), induced by cognitive tasks, healthy subjects show an increment in the respiratory rate and higher number of nonlinear interactions between respiration and HRV signal, which might be associated with a sympathetic activation, but also with a less regular breathing. In the presence of hemodynamic stress (Ch. 9.2), induced by a postural change, healthy subjects show a reduction in strength of the quadratic nonlinear cardiorespiratory coupling, whichmight be related to a vagal withdrawal. In the presence of heat stress (Ch. 9.3), induced by exposure to elevated environmental temperatures, healthy subjects show an increased sympathovagal balance. This demonstrates that ANS biomarkers are able to assess different types of stress and they can be further explored in the context of depression monitoring. In Ch. 10, differences in ANS function between MDD and healthy subjects during a mental stress protocol are assessed, not only with the raw values of ANS biomarkers but also with autonomic reactivity indices, which reflect the ability of an individual to copewith a challenging situation. Results show that depression is associated with autonomic imbalance, characterized by increased sympathetic activity and reduced arterial compliance. Autonomic reactivity indices quantified by changes, from stress to recovery, in arterial stiffness surrogates, such as the PPG amplitude loss in wave reflections, show the best performance in terms of correlation with depression severity, yielding to correlation coefficient r = −0.5. The negative correlation implies that a higher degree of depression is associated with a decreased autonomic reactivity. The discriminative power of ANS biomarkers is supported by their high diagnostic performance for classifying subjects as having MDD or not, yielding to accuracy of 80.0%. Therefore, it can be concluded that ANS biomarkers can be used for assessing stress and that impaired arterial compliance might constitute a biomarker of mental health useful in the monitoring of depression.<br /

Multivariate assessment of linear and non-linear causal coupling pathways within the central-autonomic-network in patients suffering from schizophrenia

Im Bereich der Zeitreihenanalyse richtet sich das Interesse zunehmend darauf, wie Einblicke in die Interaktions- und Regulationsprozesse von pathophysiologischen- und physiologischen Zuständen erlangt werden können. Neuste Fortschritte in der nichtlinearen Dynamik, der Informationstheorie und der Netzwerktheorie liefern dabei fundiertes Wissen über Kopplungswege innerhalb (patho)physiologischer (Sub)Systeme. Kopplungsanalysen zielen darauf ab, ein besseres Verständnis dafür zu erlangen, wie die verschiedenen integrierten regulatorischen (Sub)Systeme mit ihren komplexen Strukturen und Regulationsmechanismen das globale Verhalten und die unterschiedlichen physiologischen Funktionen auf der Ebene des Organismus beschreiben. Insbesondere die Erfassung und Quantifizierung der Kopplungsstärke und -richtung sind wesentliche Aspekte für ein detaillierteres Verständnis physiologischer Regulationsprozesse. Ziel dieser Arbeit war die Charakterisierung kurzfristiger unmittelbarer zentral-autonomer Kopplungspfade (top-to-bottom und bottom to top) durch die Kopplungsanalysen der Herzfrequenz, des systolischen Blutdrucks, der Atmung und zentraler Aktivität (EEG) bei schizophrenen Patienten und Gesunden. Dafür wurden in dieser Arbeit neue multivariate kausale und nicht-kausale, lineare und nicht-lineare Kopplungsanalyseverfahren (HRJSD, mHRJSD, NSTPDC) entwickelt, die in der Lage sind, die Kopplungsstärke und -richtung, sowie deterministische regulatorische Kopplungsmuster innerhalb des zentralen-autonomen Netzwerks zu quantifizieren und zu klassifizieren. Diese Kopplungsanalyseverfahren haben ihre eigenen Besonderheiten, die sie einzigartig machen, auch im Vergleich zu etablierten Kopplungsverfahren. Sie erweitern das Spektrum neuartiger Kopplungsansätze für die Biosignalanalyse und tragen auf ihre Weise zur Gewinnung detaillierter Informationen und damit zu einer verbesserten Diagnostik/Therapie bei. Die Hauptergebnisse dieser Arbeit zeigen signifikant schwächere nichtlineare zentral-kardiovaskuläre und zentral-kardiorespiratorische Kopplungswege und einen signifikant stärkeren linearen zentralen Informationsfluss in Richtung des Herzkreislaufsystems auf, sowie einen signifikant stärkeren linearen respiratorischen Informationsfluss in Richtung des zentralen Nervensystems in der Schizophrenie im Vergleich zu Gesunden. Die detaillierten Erkenntnisse darüber, wie die verschiedenen zentral-autonomen Netzwerke mit paranoider Schizophrenie assoziiert sind, können zu einem besseren Verständnis darüber führen, wie zentrale Aktivierung und autonome Reaktionen und/oder Aktivierung in physiologischen Netzwerken unter pathophysiologischen Bedingungen zusammenhängen.In the field of time series analysis, increasing interest focuses on insights gained how the coupling pathways of regulatory mechanisms work in healthy and ill states. Recent advances in non-linear dynamics, information theory and network theory lead to a new sophisticated body of knowledge about coupling pathways within (patho)physiological (sub)systems. Coupling analyses aim to provide a better understanding of how the different integrated physiological (sub)systems, with their complex structures and regulatory mechanisms, describe the global behaviour and distinct physiological functions at the organism level. In particular, the detection and quantification of the coupling strength and direction are important aspects for a more detailed understanding of physiological regulatory processes. This thesis aimed to characterize short-term instantaneous central-autonomic-network coupling pathways (top-to-bottom and bottom to top) by analysing the coupling of heart rate, systolic blood pressure, respiration and central activity (EEG) in schizophrenic patients and healthy participants. Therefore, new multivariate causal and non-causal linear and non-linear coupling approaches (HRJSD, mHRJSD, NSTPDC) that are able to determine the coupling strength and direction were developed. Whereby, the HRJSD and mHRJSD approaches allow the quantification and classification of deterministic regulatory coupling patterns within and between the cardiovascular- the cardiorespiratory system and the central-autonomic-network were developed. These coupling approaches have their own unique features, even as compared to well-established coupling approaches. They expand the spectrum of novel coupling approaches for biosignal analysis and thus contribute in their own way to detailed information obtained, and thereby contribute to improved diagnostics/therapy. The main findings of this thesis revealed significantly weaker non-linear central-cardiovascular and central-cardiorespiratory coupling pathways, and significantly stronger linear central information flow in the direction of the cardiac- and vascular system, and a significantly stronger linear respiratory information transfer towards the central nervous system in schizophrenia in comparison to healthy participants. This thesis provides an enhanced understanding of the interrelationship of central and autonomic regulatory mechanisms in schizophrenia. The detailed findings on how variously-pronounced, central-autonomic-network pathways are associated with paranoid schizophrenia may enable a better understanding on how central activation and autonomic responses and/or activation are connected in physiology networks under pathophysiological conditions

Multichannel near infrared spectroscopy to monitor cerebral oxygenation in infants and children supported in extracorporeal membrane oxygenation (ECMO)

Extracorporeal membrane oxygenation is a life support system for infants and children with intractable cardiorespiratory failure. The risk for developing neurological injuries in this group of patients is considerable. The causes are multifactorial and are not yet fully understood. Induction of ECMO involves ligation of the major neck vessels – common carotid artery and internal jugular vein – which may cause lateralised cerebrovascular injury. Physiologic changes such as hypoxia, hypotension and hypercarbia associated with ECMO can disrupt cerebral autoregulation. Near infrared spectroscopy (NIRS) offers the advantage of continuous non invasive means of monitoring cerebral oxygenation at the bedside. To date, NIRS systems used clinically are single or dual channel systems and do not allow evaluation of the status of cerebral circulation in the extended cerebral regions. This work involves the development of a multichannel NIRS system for use in paediatric cardiothoracic intensive care with specific application on patients supported on extracorporeal circulation. A novel flexible neonatal cap was designed and constructed to accommodate an array of sources and detectors that provide measurements of multisite cerebral oxygenation from 12 channels. Multimodal data collection (systemic and ECMO circuit parameters) simultaneous with multichannel NIRS was established to allow monitoring of multisite cerebral oxygenation and haemodynamics. A novel method of analysis, wavelet cross-correlation, was generated to study the concordance between multisite oxyhaemoglobin concentration (HbO2) and mean arterial pressure (MAP) as a means to investigate regional variations in cerebral circulation and assess cerebral autoregualtion. Group data of 6 patients showed statistically significant differences in WCC between right and left hemispheres during sequential changes in ECMO circuit blood flow. WCC between HbO2 and MAP provides a useful method to investigate the dynamics of cerebral autoregulation during ECMO. Modest manipulations of ECMO flows are associated with regional changes in cerebral autoregulation which may potentially have an important bearing on clinical outcome

Autonomic Nervous System Dynamics for Mood and Emotional-State Recognition: Wearable Systems, Modeling, and Advanced Biosignal Processing

This thesis aims at investigating how electrophysiological signals related to the autonomic nervous system (ANS) dynamics could be source of reliable and effective markers for mood state recognition and assessment of emotional responses. In-depth methodological and applicative studies of biosignals such as electrocardiogram, electrodermal response, and respiration activity along with information coming from the eyes (gaze points and pupil size variation) were performed. Supported by the current literature, I found that nonlinear signal processing techniques play a crucial role in understanding the underlying ANS physiology and provide important quantifiers of cardiovascular control dynamics with prognostic value in both healthy subjects and patients. Two main applicative scenarios were identified: the former includes a group of healthy subjects who was presented with sets of images gathered from the International Affective Picture System hav- ing five levels of arousal and five levels of valence, including both a neutral reference level. The latter was constituted by bipolar patients who were followed for a period of 90 days during which psychophysical evaluations were performed. In both datasets, standard signal processing techniques as well as nonlinear measures have been taken into account to automatically and accurately recognize the elicited levels of arousal and valence and mood states, respectively. A novel probabilistic approach based on the point-process theory was also successfully applied in order to model and characterize the instantaneous ANS nonlinear dynamics in both healthy subjects and bipolar patients. According to the reported evidences on ANS complex behavior, experimental results demonstrate that an accurate characterization of the elicited affective levels and mood states is viable only when non- linear information are retained. Moreover, I demonstrate that the instantaneous ANS assessment is effective in both healthy subjects and patients. Besides mathematics and signal processing, this thesis also contributes to pragmatic issues such as emotional and mood state mod- eling, elicitation, and noninvasive ANS monitoring. Throughout the dissertation, a critical review on the current state-of-the-art is reported leading to the description of dedicated experimental protocols, reliable mood models, and novel wearable systems able to perform ANS monitoring in a naturalistic environment

Photoplethysmography-Based Biomedical Signal Processing

In this dissertation, photoplethysmography-based biomedical signal processing methods are developed and analyzed. The developed methods solve problems concerning the estimation of the heart rate during physical activity and the monitoring of cardiovascular health. For the estimation of heart rate during physical activity, two methods are presented that are very accurate in estimating the instantaneous heart rate at the wrist and, at the same time, are computationally efficient so that they can easily be integrated into wearables. In the context of cardiovascular health monitoring, a method for the detection of atrial fibrillation using the video camera of a smartphone is proposed that achieves a high detection rate of atrial fibrillation (AF) on a clinical pre-study data set. Further monitoring of cardiovascular parameters includes the estimation of blood pressure (BP), pulse wave velocity (PWV), and vascular age index (VAI), for which an approach is presented that requires only a single photoplethysmographic (PPG) signal. Heart rate estimation during physical activity using PPG signals constitutes an important research focus of this thesis. In this work, two computationally efficient algorithms are presented that estimate the heart rate from two PPG signals using a three axis accelerometer. In the first approach, adaptive filters are applied to estimate motion artifacts that severely deteriorate the signal quality. The non-stationary relationship between the measured acceleration signals and the artifacts is modeled as a linear system. The outputs of the adaptive filters are combined to further enhance the signal quality and a constrained heart rate tracker follows the most probable high energy continuous line in the spectral domain. The second approach is modest in computational complexity and very fast in execution compared to existing approaches. It combines correlation-based fundamental frequency indicating functions and spectral combination to enhance the correlated useful signal and suppress uncorrelated noise. Additional harmonic noise damping further reduces the impact of strong motion artifacts and a spectral tracking procedure uses a linear least squares prediction. Both approaches are modest in computational complexity and especially the second approach is very fast in execution, as it is shown on a widely used benchmark data set and compared to state-of-the-art methods. The second research focus and a further major contribution of this thesis lies in the monitoring of the cardiovascular health with a single PPG signal. Two methods are presented, one for detection of AF and one for the estimation of BP, PWV, and VAI. The first method is able to detect AF based on a smartphone filming the finger placed on the video camera. The algorithm transforms the video into a PPG signal and extracts features which are then used to discriminate between AF and normal sinus rhythm (NSR). Perfect detection of AF is already achieved on a data set of 326 measurements (including 20 with AF) that were taken at a clinical pre-study using an appropriate pair of features whereby a decision is formed through a simple linear decision equation. The second method aims at estimating cardiovascular parameters from a single PPG signal without the conventional use of an additional electrocardiogram (ECG). The proposed method extracts a large number of features from the PPG signal and its first and second order difference series, and reconstructs missing features by the use of matrix completion. The estimation of cardiovascular parameters is based on a nonlinear support vector regression (SVR) estimator and compared to single channel PPG based estimators using a linear regression model and a pulse arrival time (PAT) based method. If the training data set contains the person for whom the cardiovascular parameters are to be determined, the proposed method can provide an accurate estimate without further calibration. All proposed algorithms are applied to real data that we have either recorded ourselves in our biomedical laboratory, that have been recorded by a clinical research partner, or that are freely available as benchmark data sets

EVALUACIÓN ANALGÉSICA PERIOPERATORIA DEL ACETAMINOFÉN EN PERRAS SOMETIDAS A OVARIOHISTERECTOMÍA ELECTIVA

Tesis de doctorado que evalúa el efecto analgésico del acetaminofén en perras ovarihisterectomizadas.La administración de analgésicos antiinflamatorios no esteroidales (AINES) para el control del dolor post-quirúrgico en perros es una práctica común, debido a sus efectos analgésicos, antiinflamatorios y antipiréticos. En el presente trabajo se realizaron dos estudios. En el experimento 1, el objetivo fue evaluar la analgesia post-operatoria del acetaminofén (paracetamol) a través de la utilización de las escalas de reconocimiento clínico del dolor DIVAS (Escala Dinámica e Interactiva Analógica Visual) y UMPS (Escala de la Universidad de Melbourne), en perras sometidas a ovariohisterectomía electiva. Además de valorar la seguridad y eficacia clínica del uso del acetaminofén en perros mediante pruebas de funcionamiento hepático y renal en el post-operatorio inmediato. Para ello, se utilizaron 30 perras de diferentes razas que fueron asignadas aleatoriamente a uno de los tres grupos de tratamiento: acetaminofén [GACET; n=10, 15 mg kg-1 intravenoso (IV)], carprofeno (GCARP; n=10, 4 mg kg-1 IV) y meloxicam (GMELOX; n=10, 0.2 mg kg-1 IV). Todos los tratamientos se administraron 30 minutos antes de la cirugía y posterior a esta durante 48 horas. En este período el acetaminofén se administró por vía oral cada 8 horas (15 mg kg-1); el carprofeno (4 mg kg-1) y el meloxicam (0.1 mg kg-1) se administraron por vía IV cada 24 horas. Durante el postoperatorio, los sistemas de puntuación del dolor DIVAS y UMPS fueron medidos a las 1, 2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas post-cirugía. Para evaluar la seguridad clínica de los tratamientos, se recolectaron muestras de sangre de la vena yugular para realizar la medición de enzimas ALT, AST, ALP, y los metabolitos bilirrubina directa, bilirrubina indirecta, bilirrubina total, creatinina, urea, albúmina y glucosa. Esto fue realizado en T0 (pre-anestesia; TBASAL), 48 y 96 horas después de la cirugía (T48, T96). Los resultados indican que en la evaluación clínica del dolor de todos los grupos de estudio, hubo una reducción gradual en la percepción del mismo durante el postoperatorio en ambos sistemas de puntuación; no obstante, también fue observado que ninguna escala difirió significativamente entre los tres grupos de tratamiento (P>0.05) en cada momento de evaluación durante las 48 horas post-cirugía. En cuanto a los parámetros bioquímico séricos, sólo la ALT aumentó significativamente en T96 en el GACET y GCARP con respecto a los valores basales (P<0.01). El resto de los analitos séricos evaluados se mantuvo en rangos normales. En el experimento 2 bajo el mismo diseño experimental de tratamientos administrados, el objetivo fue evaluar el efecto analgésico perioperatorio del acetaminofén 2 administrado pre y post-quirúrgicamente en perras sometidas a ovariohisterectomía electiva a través de la medición del índice de la actividad del tono parasimpático (PTA). Este parámetro hemodinámico fue medido 60 minutos antes de la cirugía (TBASAL) y durante el transquirúrgico en la aplicación de estímulos nociceptivos: colocación de las pinzas de campo backhouse (TPINZ), incisión de piel y abordaje quirúrgico primario (TINC), ligadura y extracción de pedículo ovárico izquierdo (TOVI) y derecho (TOVD), ligadura y transfixión del cuello uterino (TLIGUT), sección quirúrgica del cuello uterino (TCUT), reconstrucción de peritoneo y planos anatómicos musculares (TMUSC) y sutura de piel (TSUT). Durante el postoperatorio, el índice PTA fue valorado a las 1, 2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas, en los mismos tiempos en que fueron evaluadas las escalas de reconocimiento de dolor DIVAS y UMPS. Los resultados obtenidos en la medición del índice PTA basal para GACET fue 65 ± 8, para GCARP 65 ± 7 y para GMELOX 62 ± 5. Durante los diferentes tiempos transquirúrgicos, los valores promedio de índice PTA indican que GACET (76 ± 14) y GMELOX (72 ± 18) muestran tendencia a manifestar mayores niveles en comparación con GCARP (62 ± 13) desde el inicio del procedimiento quirúrgico sin que esto pudiera comprobarse estadísticamente, ya que no hubo diferencias significativas entre grupos de tratamiento ni entre los tiempos quirúrgicos evaluados (P>0.05). En el postoperatorio, el índice PTA fue de 65 ± 9 en el GACET, 63 ± 8 en el GCARP y 65 ± 8 en el GMELOX. Los resultados tampoco mostraron diferencias estadísticamente significativas con los valores basales o entre los tratamientos (P>0.05). El índice PTA postoperatorio mostró una sensibilidad del 40%, especificidad del 98.46% y valor predictivo negativo del 99.07% con respecto a la escala validada de UMPS. En conclusión, el acetaminofén puede considerarse una herramienta para el tratamiento efectivo del dolor perioperatorio agudo en perros, ya que mostró la misma eficacia clínica que el meloxicam y el carprofeno para la analgesia postquirúrgica en perras sometidas a ovariohisterectomía electiva. Además, la evidencia del uso de este medicamento no condujo a reacciones adversas o cambios en los parámetros evaluados, lo que indica su seguridad clínica. Finalmente, destacar que el índice PTA representa una medición objetiva del comfort y analgesia postoperatoria, por lo que es una herramienta que podría ayudar a predecir las respuestas hemodinámicas asociadas con el dolor

Remote Assessment of the Cardiovascular Function Using Camera-Based Photoplethysmography

Camera-based photoplethysmography (cbPPG) is a novel measurement technique that allows the continuous monitoring of vital signs by using common video cameras. In the last decade, the technology has attracted a lot of attention as it is easy to set up, operates remotely, and offers new diagnostic opportunities. Despite the growing interest, cbPPG is not completely established yet and is still primarily the object of research. There are a variety of reasons for this lack of development including that reliable and autonomous hardware setups are missing, that robust processing algorithms are needed, that application fields are still limited, and that it is not completely understood which physiological factors impact the captured signal. In this thesis, these issues will be addressed. A new and innovative measuring system for cbPPG was developed. In the course of three large studies conducted in clinical and non-clinical environments, the system’s great flexibility, autonomy, user-friendliness, and integrability could be successfully proven. Furthermore, it was investigated what value optical polarization filtration adds to cbPPG. The results show that a perpendicular filter setting can significantly enhance the signal quality. In addition, the performed analyses were used to draw conclusions about the origin of cbPPG signals: Blood volume changes are most likely the defining element for the signal's modulation. Besides the hardware-related topics, the software topic was addressed. A new method for the selection of regions of interest (ROIs) in cbPPG videos was developed. Choosing valid ROIs is one of the most important steps in the processing chain of cbPPG software. The new method has the advantage of being fully automated, more independent, and universally applicable. Moreover, it suppresses ballistocardiographic artifacts by utilizing a level-set-based approach. The suitability of the ROI selection method was demonstrated on a large and challenging data set. In the last part of the work, a potentially new application field for cbPPG was explored. It was investigated how cbPPG can be used to assess autonomic reactions of the nervous system at the cutaneous vasculature. The results show that changes in the vasomotor tone, i.e. vasodilation and vasoconstriction, reflect in the pulsation strength of cbPPG signals. These characteristics also shed more light on the origin problem. Similar to the polarization analyses, they support the classic blood volume theory. In conclusion, this thesis tackles relevant issues regarding the application of cbPPG. The proposed solutions pave the way for cbPPG to become an established and widely accepted technology