Alexander Caicedo

A Novel Algorithm for the Automatic Detection of Sleep Apnea From Single-Lead ECG

Goal: This paper presents a methodology for the automatic detection of sleep apnea from single-lead ECG. Methods: It uses two novel features derived from the ECG, and two well-known features in heart rate variability analysis, namely the standard deviation and the serial correlation coefficients of the RR interval time series. The first novel feature uses the principal components of the QRS complexes, and it describes changes in their morphology caused by an increased sympathetic activity during apnea. The second novel feature extracts the information shared between respiration and heart rate using orthogonal subspace projections. Respiratory information is derived from the ECG by means of three state-of-the-art algorithms, which are implemented and compared here. All features are used as input to a least-squares support vector machines classifier, using an RBF kernel. In total, 80 ECG recordings were included in the study. Results: Accuracies of about 85% are achieved on a minute-by-minute basis, for two independent datasets including both hypopneas and apneas together. Separation between apnea and normal recordings is achieved with 100% accuracy. In addition to apnea classification, the proposed methodology determines the contamination level of each ECG minute. Conclusion: The performances achieved are comparable with those reported in the literature for fully automated algorithms. Significance: These results indicate that the use of only ECG sensors can achieve good accuracies in the detection of sleep apnea. Moreover, the contamination level of each ECG segment can be used to automatically detect artefacts, and to highlight segments that require further visual inspection.

Cerebral Tissue Oxygenation and Regional Oxygen Saturation Can Be Used to Study Cerebral Autoregulation in Prematurely Born Infants

The coupling of cerebral intravascular oxygenation (dHbD) with mean arterial blood pressure (MABP) was taken as a reflection of autoregulation assuming constant arterial oxygen content. However, this method is sensitive to movement artifacts. We examined whether the cerebral tissue oxygenation index (cTOI) and regional oxygen saturation (rScO2) may replace dHbD and changes in total Hb (dHbT), respectively. Correlation (COR) and coherence (COH) were used to measure the agreement of MABP with rScO2/dHbT and cTOI/dHbD. dHbD/cTOI and dHbT/rScO2 recordings of, respectively, 34 and 20 preterm infants in need for intensive care were studied during the first days of life. dHbD and cTOI were obtained with the NIRO300 and rScO2 and dHbT with the INVOS4100. Invasive MABP was measured continuously. COR and COH scores of MABP versus dHbD/dHbT were compared with the corresponding ones by replacing dHbD/dHbT by cTOI/rScO2, respectively. Generally, no significant score differences were found for dHbD/cTOI. Differences for dHbT/rScO2 were slightly larger but still within the normal variation of the parameters. Differences become insignificant when restricting calculations to epochs of larger variation in MABP (>10 mm Hg). Hence, we suggest that cTOI and rScO2 can be used to study cerebral autoregulation in newborns.

Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates

Background:Currently, reliable reference values of regional cerebral oxygen saturation (rScO2) for different gestational age (GA) groups are lacking, which hampers the implementation of near-infrared spectroscopy (NIRS) alongside monitoring arterial oxygen saturation (SaO2) and blood pressure in neonatal intensive care. The aim of this study was to provide reference values for rScO2 and cerebral fractional tissue oxygen extraction (cFTOE; (SaO2 − rScO2)/SaO2) for small adult and neonatal NIRS sensors.Methods:In this study, 999 infants born preterm (GA <32 wk) were monitored with NIRS during the first 72 h of life. Mixed modeling was used to generate reference curves grouped per 2 wk of GA. In addition, the influence of a hemodynamically significant patent ductus arteriosus, gender, and birth weight were explored.Results:Average rScO2 was ~65% at admission, increased with GA (1% per week) and followed a parabolic curve in relation to postnatal age with a peak at ~36 h. The cFTOE showed similar but inverse effects. On average, the neonatal sensor measured 10% higher than the adult sensor.Conclusion:rScO2 and cFTOE reference curves are provided for the first 72 h of life in preterm infants, which might support the broader implementation of NIRS in neonatal intensive care.

Impaired Cerebral Autoregulation Using Near-Infrared Spectroscopy and Its Relation to Clinical Outcomes in Premature Infants

The concordance between the change in the Mean Arterial Blood Pressure (MABP) and the Cerebral Blood Flow (CBF) is studied using the Correlation, Coherence and Partial Coherence methods in order to detect Impaired Cerebral Autoregulation in Neonates. The presence of impaired autoregulation is assessed by the use of the Critical Percentage of Recording Time (CPRT). The changes in CBF are reflected by the measurement of changes in cerebral intravascular oxygenation (HbD), regional cerebral oxygen saturation (rSO(2)), and cerebral tissue oxygenation (TOI), as measured by Near-Infrared Spectroscopy (NIRS) (INVOS4100 and NIRO300). The relation between impaired autoregulation and long term clinical outcomes in premature infants is studied.

Detection of cerebral autoregulation by near-infrared spectroscopy in neonates: performance analysis of measurement methods

Abstract. Cerebral Autoregulation, in clinical practice, is assessed by means of correlation or coherence analysis between mean arterial blood pressure (MABP) and cerebral blood flow (CBF). However, even though there is evidence linking cerebral autoregulation assessment with clinical outcome in preterm infants, available methods lack precision for clinical use. Classical methods, used for cerebral autoregulation, are influenced by the choice of parameters such as the length of the epoch under analysis and the choice of suitable frequency bands. The influence of these parameters, in the derived measurements for cerebral autoregulation, has not yet been evaluated. In this study, cerebral autoregulation was assessed using correlation, coherence, a modified version of coherence and transfer function gain, and phase. The influence of the extra-parameters on the final scores was evaluated by means of sensitivity analysis. The methods were applied to a database of 18 neonates with measurements of MABP and tissue oxygenation index (TOI). TOI reflects changes in CBF and was measured by means of near-infrared spectroscopy.

Propofol Dose-Finding to Reach Optimal Effect for (Semi-)Elective Intubation in Neonates

OBJECTIVE To define the effective dose for 50% of patients (ED50) of propofol for successful intubation and to determine the rate of successful extubation in those patients with planned intubation, surfactant administration, and immediate extubation (INSURE procedure). In addition, pharmacodynamic effects were assessed. STUDY DESIGN Neonates (n = 50) treated with propofol for (semi-)elective endotracheal intubation were stratified in 8 strata by postmenstrual and postnatal age. The first patient in each stratum received an intravenous bolus of 1 mg/kg propofol. Dosing for the next patient was determined using the up-and-down method. A propofol ED50 dose was calculated in each stratum with an effective sample size of at least 6, via the Dixon-Masey method, with simultaneous assessment of clinical scores and continuous vital sign monitoring. RESULTS Propofol ED50 values for preterm neonates <10 days of age varied between 0.713 and 1.350 mg/kg. Clinical recovery was not attained at the end of the 21-minute scoring period. Mean arterial blood pressure showed a median decrease between 28.5% and 39.1% from baseline with a brief decrease in peripheral and regional cerebral oxygen saturation. Variability in mean arterial blood pressure area under the curve could not be explained by weight or age. CONCLUSIONS Low propofol doses were sufficient to sedate neonates for intubation. Clinical recovery was accompanied by permissive hypotension (no clinical shock and no treatment). The propofol ED50 doses can be administered at induction, with subsequent up-titration if needed, while monitoring blood pressure. They can be used for further dosing optimalization and validation studies. TRIAL REGISTRATION ClinicalTrials.gov: NCT01621373; EudraCT: 2012-002648-26.

Oxygen transport to tissue XXXV

Preface.- Acknowledgements.- Remembering Professor Mamoru Tamura.- Part 1: Hypoxia.- Increased Kidney Metabolism as a Pathway to Kidney Tissue Hypoxia and Damage: Effects of Triiodothyronine and Dinitrophenol in Normoglycemic Rats.- Hypoxia-Induced Cerebral Angiogenesis in Mouse Cortex with Two-Photon Microscopy.- Reduction of Cytochrome c Oxidase During Vasovagal Hypoxia-Ischaemia in Human Adult Brain: A Case Study.- Increased HIF-1alpha and 2alpha Accumulation, but Decreased Microvascular Density, in Chronic Hyperoxia and Hypercapnia in the Mouse Cerebral Cortex.- Oxygen Delivery: The Principal Role of the Circulation.- Heart Rate Variability in Newborns with Hypoxic Brain Injury.- Part 2: Brain Oxygenation.- Simultaneous Monitoring of Brain and Skin Oxygenation during Haemorrhagic Shock in Piglets.- Hemispheric Differences of Motor Execution: A Near-Infrared Spectroscopy Study.- Acute Stress Exposure Preceding Global Brain Ischemia Accelerates Decreased Doublecortin Expression in the Rat Retrosplenial Cortex.- Effects of Transcranial Direct Current Stimulation of the Motor Cortex on Prefrontal Cortex Activation during a Neuromuscular Fatigue Task: An fNIRS Study.- The Effect of Inner Speech on Arterial CO2, Cerebral Hemodynamics and Oxygenation - A Functional NIRS Study.- Investigation of Frontal Lobe Activation with fNIRS and Systemic Changes during Video Gaming.- Effect of Valsalva Maneuver-induced Hemodynamic Changes on Brain Near-infrared Spectroscopy Measurements.- Cerebral Autoregulation in Premature Infants.- Brain Tissue Oxygen Saturation Increases during Sleep in Adolescents.- Changes of Cerebral Oxygen Metabolism and Hemodynamics during ECPR with Hypothermia Measured by Near Infrared Spectroscopy: A Pilot Study.- Part 3: Muscle Oxygenation.- Analysis of NIRS-based Muscle Oxygenation Parameters by Inclusion of Adipose Tissue Thickness.- Statistical Treatment of Oxygenation-related Data in Muscle Tissue.- O2 Saturation in the Intercostal Space during Moderate and Heavy Constant-load Exercise.- Muscle, Prefrontal and Motor Cortex Oxygenation Profiles during Prolonged Fatiguing Exercise.- Aging Affects Spatial Distribution of Leg Muscle Oxygen Saturation during Ramp Cycling Exercise.- Which is the Best Indicator of Muscle Oxygen Extraction during Exercise using NIRS? - Evidence that HHb is not the Candidate.- Tissue Oxygenation during Exercise Measured with NIRS: Reproducibility and Influence of Wavelengths.- Using Portable NIRS to Compare Arm and Leg Muscle Oxygenation during Roller-skiing in Bi-athletes: A Case Study.- The Use of Portable NIRS to measure Muscle Oxygenation and Haemodynamics during a Repeated Sprint Running Test.- Tumor Oxygenation.- Amifostine Acts upon Mitochondria to Stimulate Growth of Bone Marrow and Regulate Cytokines.- Hypoxia, Lactate Accumulation and Acidosis: Siblings Or Accomplices Driving Tumor Progression And Resistance To Therapy?.- Breast Cancer Detection of Large Size to DCIS by Hypoxia and Angiogenesis using NIRS.- Impact of Extracellular Acidosis on Intracellular pH Control and Cell Signaling in Tumor Cells.- Tumor Oxygenation: An Appraisal of Past and Present Concepts, and a Look into the Future.- In Vivo Metabolic Evaluation of Breast Tumor Mouse Xenografts for Predicting Aggressiveness Using the Hyperpolarized 13C-NMR Technique.- Mapping the Redox State of CHOP-treated Non-Hodgkins Lymphoma Xenografts in Mice.- Maternal Bias in Mouse Radiosensitivity: The Role of the Mitochondrial PTP.- Interleukin 11 Protects Bone Marrow Mitochondria from Radiation Damage.- Tumor Reoxygenation following Administration of the EGFR inhibitor, Gefitinib, in Experimental Tumors.- Radiation Affects the Responsiveness of Bone Marrow to G-CSF.- Application of MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) to Study Variations in Tumor Oxygenation.- Primo Vascular System and its Potential Role in Cancer Metastasis.- Part 5: Cell Metabolism.- Pancreaticoduodenectomy using Perioperative Zymogen Protein C to Help Prevent Blood Clotting. A Trilogy on Increased Patient Safety.- Inhibition of Mammalian Target of Rapamycin Induces Renal Mitochondrial Uncoupling in Rats.- Molecular Hydrogen Consumption in the Human Body during the Inhalation of Hydrogen Gas.- Oxidative Metabolism: Glucose vs Ketones.- Part 6: System Modelling.- Modelling Blood Flow and Metabolism in the Piglet Brain during Hypoxia-ischaemia: Simulating pH Changes.- Modelling Blood Flow and Metabolism in the Piglet Brain during Hypoxic-ischaemia: Simulating Brain Energetics.- Mathematical Modelling of Near Infrared Spectroscopy Signals and Intracranial Pressure in Brain Injured Patients.- Dependence on NIRS Source-Detector Spacing of Cytochrome C Oxidase Response to Hypoxia and Hypercapnia in the Adult Brain.- Modeling Hemoglobin Nitrite Reductase Activity as a Mechanism of Hypoxic Vasodilation?.- Part 7: Measurement Technologies.- Development of a Hybrid Microwave-optical Tissue Oxygenation Probe to Measure Thermal Response in the Deep Tissue.- Oxygen Sensitive Quantum Dots for Possible Nano-scale Oxygen Imaging in Cultured Cells.- Boron Tracedrug Design for Neutron Dynamic Therapeutics for LDL.- New Method of Analysing NIRS Data from Prefrontal Cortex at Rest.- Radiation Oxygen Biology with Pulse Electron Paramagnetic Resonance Imaging in Animal Tumors.- Wavelength Selection for the Improvement of the Signal to Noise Ratio for Imaging of Haemoglobin Oxygenation with RGB Reflectometry.- Improving Pulse Oximetry Accuracy by Removing Motion Artifacts from Photoplethysmograms using Relative Sensor Motion: A Preliminary Study.- Measuring the Vascular Diameter of Brain Sur-face and Parenchymal Arteries in Awake Mouse.- Simultaneous Imaging of Cortical Blood Flow and Haemoglobin Concentration with LASCA and RGB Reflectometry.- Quality Evaluation Method for Rat Brain Cryofixation Based on NADH Fluorescence.- Cerebral Cortex Activation Mapping upon Electrical Muscle Stimulation by 32-channel Time Domain Functional Near Infrared Spectroscopy.- NIRS-based Neurofeedback Learning Systems for Controlling Activity of the Prefrontal Cortex.- Cortical Mapping of 3D Optical Topography in Infants.- Monitoring of Hemodynamic Change in Patients with Carotid Artery Stenosis during the Tilt Test using Wearable Near-infrared Spectroscopy.- Index.

Canonical Correlation Analysis in the Study of Cerebral and Peripheral Haemodynamics Interrelations with Systemic Variables in Neonates Supported on ECMO

Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury due to haemodynamic instability. In order to monitor cerebral and peripheral (muscle) haemodynamic and oxygenation changes in this population we used a dual-channel near-infrared spectroscopy (NIRS) system. In addition, to assess interrelations between NIRS and systemic variables, collected simultaneously, canonical correlation analysis (CCA) was employed. CCA can quantify the relationship between a set of variables and assess levels of dependency. In four out of five patients, systemic variables were found to be less inter-related with cerebral rather than peripheral NIRS measurements. Moreover, during ECMO flow manipulations, we found that the interrelation between the systemic and the NIRS cerebral/peripheral variables changed. The CCA method presented here can be used to assess differences between NIRS cerebral and NIRS peripheral responses due to systemic variations which may be indicative of physiological differences in the mechanisms that regulate oxygenation and/or haemodynamics of the brain and the muscle.

Influence of the Maternal Use of Labetalol on the Neurogenic Mechanism for Cerebral Autoregulation Assessed by Means of NIRS

Labetalol is a drug used in the treatment of hypertensive disorders of pregnancy (HDP). In a previous study we investigated the influence of the maternal use of labetalol on the cerebral autoregulation (CA) mechanism of neonates. In that study, we found that labetalol induces impaired CA during the first day of life, with CA returning to a normal status by the third day after birth. This effect was hypothesized to be caused by labetalol-induced vasodilation. However, no strong evidence for this claim was found. In this study we aim to find stronger evidence for the vasodilation effect caused by labetalol, by investigating its effect on the neurogenic mechanism (NM) involved in CA. The status of the NM was assessed by means of transfer function analysis between the low frequency content of the autonomic control activity (LFA), obtained by processing of the heart rate (HR), and the regional cerebral oxygen saturation (rScO₂). We found that neonates from mothers treated with labetalol presented a lower LFA and an impaired NM response during the first day of life, with values returning to normal by the end of the third day. These results reflect a vasodilation effect caused by labetalol, and indicate that the impaired CA observed in the previous study is caused by vasodilation.

Effect of maternal use of labetalol on the cerebral autoregulation in premature infants.

Hypertensive disorders of pregnancy (HDP) are normally treated to avoid maternal complications. In this study we aimed to investigate if there was an effect of maternal HDP treatment on the cerebral autoregulation of the neonates by analysing measurements of mean arterial blood pressure (MABP) and rScO2 by means of correlation, coherence, and transfer function analysis. We found that these infants presented higher values of transfer function gain, which indicates impaired cerebral autoregulation, with a decreasing trend towards normality. We hypothesised that this trend was due to a vasodilation effect of the maternal use of labetalol due to accumulation, which disappeared by the third day after birth. Therefore, we investigated the values of pulse pressure in order to find evidence for a vasodilatory effect. We found that lower values of pulse pressure were present in these infants when compared with a control population, which, together with increased transfer function gain values, suggests an effect of the drug on the cerebral autoregulation.