Cardiorespiratory Coherence Analysis of Abnormal Heart Rate Responses during Deep Breathing

Abstract Although the heart rate variability (HRV

Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates

Abstract: Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication.For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury.Continuous multimodal monitoring as well as monitoring of sleep, sleep–wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care

Retinal vascular reactivity study using optical coherence tomography angiography

A retina, o tecido que mais oxigénio consome por unidade de área, possui um complexo sistema de autorregulação vascular. Este mecanismo permite manter o adequado fornecimento de oxigénio e nutrientes à retina em condições de hipóxia ou alterações da pressão arterial, por exemplo. Na maior parte dos estudos existentes, as respostas vasculares da retina foram avaliadas com recurso a técnicas de imagem que se limitam à avaliação dos vasos de maior calibre. A possibilidade de analisar em maior detalhe estes mecanismos poderá ajudar a compreender melhor os processos envolvidos na autorregulação microvascular da retina, tanto em condições fisiológicas como de doença. A angiografia por tomografia de coerência ótica (OCTA) é um exame rápido, seguro, não-invasivo, tridimensional e de alta resolução da microvasculatura retiniana. O objetivo principal desta tese foi estudar a reatividade vascular da retina usando OCTA, em indivíduos saudáveis e com diabetes tipo 1 (DM1), e discutir potenciais aplicações clínicas. Nesse sentido, desenvolvemos uma série de trabalhos experimentais multidisciplinares. A primeira publicação constitui a prova de conceito sobre a capacidade daOCTA detetar uma resposta vascular retiniana. No segundo artigo, utilizou-se OCTA para estudar alterações microvasculares estruturais da retina em pacientes com DM1 sem retinopatia. O terceiro manuscrito consiste num protocolo metodológico em que a OCTA é utilizado para estudar respostas vasculares retinianas a estímulos vasodilatadores e vasoconstritores, utilizando dois testes padronizados - hipóxia e exercício isométrico, respetivamente. Na última publicação, aplicou-se este protocolo a doentes com DM1 sem evidência de retinopatia, e verificou-se que estes apresentam alterações nas respostas autorregulatórias da retina. Os estudos realizados no âmbito desta tese destacam o potencial de otimização da tecnologia OCTA no sentido de combinar uma análise funcional ao angiograma estrutural atualmente isponível. A metodologia desenvolvida nesta tese para o estudo da microcirculação retiniana constitui um ponto de partida para futuras aplicações clínicas da OCTA, não só em Oftalmologia mas também em outras áreas, como a Medicina Cardiovascular e Neurociências.As the highest oxygen-consuming tissue of the human body, the retina has evolved to have an intricate vascular autoregulatory system. This mechanism ensures adequate supply of oxygen and nutrients to retinal tissues in conditions such as high blood pressure or hypoxia. Most studies on retinal vascular responses used imaging techniques that were limited to the assessment of the larger vessels. Novel and more detailed ways of analysing retinal vascular responses could provide insights on retinal autoregulation in both health and disease. Optical coherence tomography angiography (OCTA) allows a fast, safe, non-invasive and three-dimensional angiographic scan of the retinal microvasculature with unprecedented high-resolution. The main goal of this thesis was to dynamically study retinal vascular reactivity in healthy subjects and in a cohort of patients with type 1 diabetes (T1D) using OCTA, and to explore potential applications in ophthalmology and other medical fields. With this purpose, we developed a series of experimental multidisciplinary works. The first publication constitutes the proof of concept on the capacity of OCTA to detect a retinal vascular response. In the second, OCTA was used to study early structural retinal microvascular changes in patients with T1D before clinically evident retinopathy. The third paper consists of a methodological protocol on the use of OCTA to study retinal vascular responses of both vasodilation and vasoconstriction, using two standardized stress tests – hypoxia and isometric exercise. The last publication applied these methods to the disease setting (i.e. T1D patients with no evidence of retinopathy), and significant changes in retinal autoregulatory responses were found. The studies developed within this thesis highlight the potential of optimizing OCTA technology in order to combine a functional analysis to the currently available single structural angiogram. It provides a basis for future applications of this concept in ophthalmology and many other fields, such as neurological and cardiovascular research.Bolsa de Doutoramento da Universidade de Lisboa14ª Bolsa Investigação Fundação AstraZeneca/FMU

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

Evidence and clinical relevance of maternal-fetal cardiac coupling:A scoping review

BACKGROUND: Researchers have long suspected a mutual interaction between maternal and fetal heart rhythms, referred to as maternal-fetal cardiac coupling (MFCC). While several studies have been published on this phenomenon, they vary in terms of methodologies, populations assessed, and definitions of coupling. Moreover, a clear discussion of the potential clinical implications is often lacking. Subsequently, we perform a scoping review to map the current state of the research in this field and, by doing so, form a foundation for future clinically oriented research on this topic.METHODS: A literature search was performed in PubMed, Embase, and Cochrane. Filters were only set for language (English, Dutch, and German literature were included) and not for year of publication. After screening for the title and the abstract, a full-text evaluation of eligibility followed. All studies on MFCC were included which described coupling between heart rate measurements in both the mother and fetus, regardless of the coupling method used, gestational age, or the maternal or fetal health condition.RESULTS: 23 studies remained after a systematic evaluation of 6,672 studies. Of these, 21 studies found at least occasional instances of MFCC. Methods used to capture MFCC are synchrograms and corresponding phase coherence indices, cross-correlation, joint symbolic dynamics, transfer entropy, bivariate phase rectified signal averaging, and deep coherence. Physiological pathways regulating MFCC are suggested to exist either via the autonomic nervous system or due to the vibroacoustic effect, though neither of these suggested pathways has been verified. The strength and direction of MFCC are found to change with gestational age and with the rate of maternal breathing, while also being further altered in fetuses with cardiac abnormalities and during labor.CONCLUSION: From the synthesis of the available literature on MFCC presented in this scoping review, it seems evident that MFCC does indeed exist and may have clinical relevance in tracking fetal well-being and development during pregnancy.</p

Multimodal Signal Processing for Diagnosis of Cardiorespiratory Disorders

This thesis addresses the use of multimodal signal processing to develop algorithms for the automated processing of two cardiorespiratory disorders. The aim of the first application of this thesis was to reduce false alarm rate in an intensive care unit. The goal was to detect five critical arrhythmias using processing of multimodal signals including photoplethysmography, arterial blood pressure, Lead II and augmented right arm electrocardiogram (ECG). A hierarchical approach was used to process the signals as well as a custom signal processing technique for each arrhythmia type. Sleep disorders are a prevalent health issue, currently costly and inconvenient to diagnose, as they normally require an overnight hospital stay by the patient. In the second application of this project, we designed automated signal processing algorithms for the diagnosis of sleep apnoea with a main focus on the ECG signal processing. We estimated the ECG-derived respiratory (EDR) signal using different methods: QRS-complex area, principal component analysis (PCA) and kernel PCA. We proposed two algorithms (segmented PCA and approximated PCA) for EDR estimation to enable applying the PCA method to overnight recordings and rectify the computational issues and memory requirement. We compared the EDR information against the chest respiratory effort signals. The performance was evaluated using three automated machine learning algorithms of linear discriminant analysis (LDA), extreme learning machine (ELM) and support vector machine (SVM) on two databases: the MIT PhysioNet database and the St. Vincent’s database. The results showed that the QRS area method for EDR estimation combined with the LDA classifier was the highest performing method and the EDR signals contain respiratory information useful for discriminating sleep apnoea. As a final step, heart rate variability (HRV) and cardiopulmonary coupling (CPC) features were extracted and combined with the EDR features and temporal optimisation techniques were applied. The cross-validation results of the minute-by-minute apnoea classification achieved an accuracy of 89%, a sensitivity of 90%, a specificity of 88%, and an AUC of 0.95 which is comparable to the best results reported in the literature

The effects of an integrated exercise and recreation therapy intervention on breast cancer survivors

Researchers investigated effects of a 20-week integrative intervention (IIG) assessing the physical and psychosocial health of breast cancer survivors. This retrospective study included 70 survivors randomized into 4 groups: IIG, exercise only (EX), recreation therapy only (RT), or control group (CO) and assessed at baseline, week 8, and post intervention. Three days a week the IIG exercised at low to moderate-intensity 60 minutes, and recreation therapy 30 minutes, EX did exercise only, RT did recreation therapy only and the control group, no intervention for the first 8 weeks. Following week 8 assessments, all groups received IIG intervention. Results revealed that the IIG promoted positive changes in cardiorespiratory function (p= .001), muscular fitness (p≤.0005), fatigue (p≤.0005), and quality of life (p= .001) within the first 8 weeks of a 20-week rehabilitation program. In conclusion, a combined exercise and psychosocial intervention promotes improvements in physiological and psychological needs of breast cancer survivors

Cardiovascular autonomic control after spinal cord injury: Comprehensive investigations into classification and care

Over 86,000 Canadians live with the consequences of a spinal cord injury (SCI). Injury to spinal autonomic pathways can lead to profound cardiovascular autonomic dysfunction. Key areas of concern identified by individuals living with SCI relate to continence and cardiovascular dysfunction. Conditions that result from autonomic dysfunction, such as autonomic dysreflexia (sudden extreme hypertension) are of particular concern. This thesis examined the cardiovascular autonomic consequences of SCI and their relationship to bowel care, the most potent stimulus for dysreflexia, and a key factor that negatively impacts quality of life after SCI. To assess cardiovascular autonomic control, first a quantitative marker of autonomic dysfunction following SCI had to be identified. In Aim 1 (Chapter 3), cardiovascular dysfunction during, and beyond, the first year of injury (n=63) was assessed using a novel quantitative non-invasive marker of cardiovascular autonomic control. From here, a randomized double-blind placebo-controlled crossover clinical trial to determine the effect of topical afferent blockade (lidocaine) on dysreflexia severity during bowel care was conducted (n=13). Aim 2 (Chapter 4) provides evidence that, contrary to current clinical guidelines, topical lidocaine prolongs bowel care, worsens dysreflexia, and increases cardiovascular symptoms. Despite bowel care concerns, past research shows that individuals do not change bowel care practices, highlighting knowledge translation gaps concerning evidence-based bowel management strategies. To address this, in Aim 3 (Chapter 5), semi-structured interviews (n=13) were used to examine the barriers and facilitators to changing bowel care. The largest influences on changing bowel care and potentially relevant intervention options were identified. Finally, during dysreflexia profound sympathetic stimulation may increase risk for cardiac arrhythmia. Aim 4 (Chapter 6) evaluated susceptibility to arrhythmia in a rodent-model of SCI, the impact of the sympathomimetic drug dobutamine on arrhythmia risk, and the potential mitigating effect of exercise training. SCI increased susceptibility to cardiac arrhythmia, with dobutamine further increasing susceptibility in high-level SCI. Exercise training ameliorated markers of arrhythmia risk during dobutamine. The research conducted in this thesis uses a translational and patient-orientated approach to bridge the gap between physiological understanding and meaningful improvement in the clinical setting for individuals living with cardiovascular and continence implications of SCI