Cerebral Tissue Oxygenation Research Articles

Near-Infrared Spectroscopy (NIRS) in the Assessment of Cerebral Tissue Oxygenation (rSO2): Methodological Issues and Dilemmas

Introduction: Monitoring cerebral perfusion in patients with brain injury is a major clinical challenge. Monitoring cerebral oxygenation (rSO2) via NIRS was introduced in the early 1980s, and many clinicians believed it to be a valuable method for assessing cerebral perfusion and subsequent measures to optimize cerebral flow. The main problem with the use of NIRS is the presence of intermediate structures—the skin, skull, meninges, cerebrospinal fluid—and their influence on the test result. Therefore, it seems that NIRS assessment performed on a patient during brain death can give an idea of the magnitude of the influence of these intermediate structures on the monitoring result. Case presentation: We present a case study of cerebral oxygenation measurements in a patient undergoing a brain death diagnostic procedure. A clinical situation in which cerebral blood flow is stopped can give an idea of the specificity of this method, in particular of the influence of intermediate structures on the monitoring result. In this case, the result obtained using NIRS is increased by the patient’s oxygenation before the apnea test. The influence of chromophores in the tissues surrounding the CNS and reflections and scattering of the light wave spectrum have a very significant effect on the final result of cerebral saturation measurement. Discussion: The majority of observations in existing research describing changes in cerebral perfusion or its optimization may be burdened by the problem described here, i.e., by the significant influence of measured intermediate structure oxygenation. The specificity of NIRS in assessing cerebral perfusion requires careful analysis. The therapeutic implications of monitoring cerebral oxygenation with NIRS are of great importance, and based on the example presented and the literature provided, this method should be used with caution. It has been shown that in a patient with brain death, the result of NIRS oxygenation measurements depends on the structures surrounding the brain.

Blood pressure and cerebral oxygenation with physiologically-based cord clamping: sub-study of the BabyDUCC trial

BackgroundCord-clamping strategies may modify blood pressure (BP) and cerebral tissue oxygen saturation (rStO2) immediately after birth.MethodsWe conducted a sub-study nested within the Baby-Directed Umbilical Cord-Clamping trial. Infants ≥32+0 weeks’ gestation assessed as requiring resuscitation were randomly allocated to either physiologically-based cord clamping (PBCC), where resuscitation commenced prior to umbilical cord clamping, or standard care where cord clamping occurred early (ECC). In this single-site sub-study, we obtained additional measurements of pre-ductal BP and rStO2. In a separate observational arm, non-randomised vigorous infants received 2 min of deferred cord clamping (DCC) and contributed data for reference percentiles.ResultsAmong 161 included infants, n = 55 were randomly allocated to PBCC (n = 30) or ECC (n = 25). The mean (SD) BP at 3–4 min after birth (primary outcome) in the PBCC group was 64 (10) mmHg compared to 62 (10) mmHg in the ECC group, mean difference 2 mmHg (95% confidence interval −3–8 mmHg, p = 0.42). BP and rStO2 were similar across both randomised arms and the observational arm (n = 106).ConclusionWe found no difference in BP or rStO2 with the different cord clamping strategies. We report reference ranges for BP and rStO2 for late-preterm and full-term infants receiving DCC.ImpactAmong late-preterm and full-term infants receiving varying levels of resuscitation, blood pressure (BP, at 3–4 minutes and 6 min) and cerebral tissue oxygen saturation (rStO2) are not influenced by timing of cord clamping in relation to establishment of ventilation.Infants in this study did not require advanced resuscitation, where cord clamping strategies may yet influence BP and rStO2.The reference ranges for BP and rStO2 represent the first, to our knowledge, for vigorous late-preterm and full-term infants receiving deferred cord clamping.rStO2 > 90% (~90th percentile) may be used to define cerebral hyperoxia, for instance when studying oxygen supplementation after birth.

Results of using thoraflextm hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital

Background: The aim of this study was to introduce and evaluate the early results after the frozen elephant trunk (FET) procedure with ThoraflexTM Hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital. Methods: This is a retrospective descriptive study of all acceptable patients after the frozen elephant trunk (FET) procedure with ThoraflexTM Hybrid prothesis at Viet Duc University Hospital from January 2021 to May 2023. Results: There were 21 patients with a male rate of 85.7% and an average age 58.2±10 years old (range 40–73). History of patients with hypertension: 19 (90.5%); post-dissection aortic aneurysm: 2 (9.5%) patients. By cause, the number of patients with thoracic aortic aneurysm was 03 (14.3%), acute aortic dissection type A was 16 (76.1%), and aortic dissection type B was 02 (9.5%). In which there were 16 cases of emergency surgery (76.1%). Replacement of the aortic arch was performed under moderate hypothermic (280 °C on average) circulatory arrest and bilateral selective antegrade cerebral perfusion with permanent monitoring of cerebral tissue oxygenation by the MASIMO machine. Average cardio-pulmonary bypass time, aortic cross clamp time, distal hypothermic circulatory arrest time, and operating time were 137,5±22,9 minutes; 86,3±17,6 minutes; 25,2±8,9 minutes; and 7,7±10,3 hours. The average ventilation time, length of intensive care unit stay, and hospital stay were 7,2±9,7 days, 18,8±20,7 days, and 19,9 ± 6,5 days. There was one patient with post-operative cerebrospinal fluid drainage. No patient had bleeding complications, recurrent nerve palsy, reoperation, or in-hospital mortality. Conclusion: The initial results after the frozen elephant trunk procedure with ThoraflexTM Hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital were safe, good, and feasible.

Application of the Single Source-Detector Separation Algorithm in Wearable Neuroimaging Devices: A Step toward Miniaturized Biosensor for Hypoxia Detection.

Most currently available wearable devices to noninvasively detect hypoxia use the spatially resolved spectroscopy (SRS) method to calculate cerebral tissue oxygen saturation (StO2). This study applies the single source-detector separation (SSDS) algorithm to calculate StO2. Near-infrared spectroscopy (NIRS) data were collected from 26 healthy adult volunteers during a breath-holding task using a wearable NIRS device, which included two source-detector separations (SDSs). These data were used to derive oxyhemoglobin (HbO) change and StO2. In the group analysis, both HbO change and StO2 exhibited significant change during a breath-holding task. Specifically, they initially decreased to minimums at around 10 s and then steadily increased to maximums, which were significantly greater than baseline levels, at 25-30 s (p-HbO < 0.001 and p-StO2 < 0.05). However, at an individual level, the SRS method failed to detect changes in cerebral StO2 in response to a short breath-holding task. Furthermore, the SSDS algorithm is more robust than the SRS method in quantifying change in cerebral StO2 in response to a breath-holding task. In conclusion, these findings have demonstrated the potential use of the SSDS algorithm in developing a miniaturized wearable biosensor to monitor cerebral StO2 and detect cerebral hypoxia.

Coupling between Regional Oxygen Saturation of the Brain and Vital Signs during Immediate Transition after Birth

Introduction: The primary aim was to analyze any coupling of heart rate (HR)/arterial oxygen saturation (SpO₂) and regional cerebral oxygen saturation (rScO₂) and regional cerebral fractional tissue oxygen extraction (cFTOE) during immediate transition after birth in term and preterm neonates to gain more insight into interactions. Methods: The present study is a post hoc analysis of data from 106 neonates, obtained from a prospective, observational study. Measurements of HR, SpO₂, rScO₂, and cFTOE were performed during the first 15 min after birth. The linear and nonlinear correlation were computed between these parameters in a sliding window. The resulting coupling curves were clustered. After clustering, demographic data of the clusters were de-blinded and compared. Results: Due to missing data, 58 out of 106 eligible patients were excluded. Two clusters were obtained: cluster 1 (N = 39) and cluster 2 (N = 9). SpO₂ had linear and nonlinear correlations with rScO₂ and cFTOE, whereby the correlations with rScO₂ were more pronounced in cluster 2. HR-rScO₂ and HR-cFTOE demonstrated a nonlinear correlation in both clusters, again being more pronounced in cluster 2, whereby linear correlations were mainly absent. After de-blinding, the demographic data revealed that the neonates in cluster 2 had significantly lower gestational age (mainly preterm) compared to cluster 1 (mainly term). Discussion: Besides SpO₂, also HR demonstrated a nonlinear correlation with rScO₂ and cFTOE in term and preterm neonates during immediate transition after birth. In addition, the coupling of SpO₂ and HR with cerebral oxygenation was more pronounced in neonates with a lower gestational age.

Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Impact of catheterized ductal closure on renal and cerebral oximetry in premature neonates.

Percutaneous catheter-based closure is increasingly utilized in premature newborns. While near-infrared spectroscopy (NIRS) has been examined for assessment of interventional closure in surgical ligation, its application in percutaneous transcatheter closure remains unexplored. This study aims to assess cerebral and renal hemodynamic changes using NIRS during percutaneous closure compared to surgical closure in preterm infants. A prospective observational study enrolled preterm infants born at 32 weeks of gestation or less and diagnosed with hsPDA between January 2020 and December 2022. These infants received either surgical or catheter-based closure of the PDA. Cerebral and renal oxygen saturation was monitored using the INVOS 5100 device from 12 h before the intervention until 24 h after. Linear mixed-effects models were used to analyze time-dependent variables. Twenty-two patients were enrolled, with catheter-based closure performed in 16 cases and conventional surgery in 6 cases. Following ductal closure, a significant increase in renal and cerebral oximetry was observed alongside a decrease in renal and cerebral tissue oxygen extraction. These changes were particularly pronounced in the renal territory. No differences were detected between catheterization and surgical closure. Conclusion: An improvement in cerebral and renal oximetry following hsPDA closure was observed. However, we did not identify differences in this pattern based on the type of interventional procedure for PDA, whether surgery or catheterization. What is Known: •The presence of a significant ductus is common in premature patients. Studies have shown that it affects cerebral and renal hemodynamics negatively, leading to decreased oximetry values in these areas. It has been reported that closure of the ductus, either pharmacologically or surgically, results in improved oximetry values. What is New: •This study assess the impact of percutaneous closure of ductus, revealing increased oximetry values in cerebral and renal territories without significant differences compared to surgical ligation. Notably, renal oximetry values showed a greater increase, underscoring the importance of multi-location monitoring.

Hemorrhage at high altitude: impact of sustained hypobaric hypoxia on cerebral blood flow, tissue oxygenation, and tolerance to simulated hemorrhage in humans.

With ascent to high altitude (HA), compensatory increases in cerebral blood flow and oxygen delivery must occur to preserve cerebral metabolism and consciousness. We hypothesized that this compensation in cerebral blood flow and oxygen delivery preserves tolerance to simulated hemorrhage (via lower body negative pressure, LBNP), such that tolerance is similar during sustained exposure to HA vs. low altitude (LA). Healthy humans (4F/4M) participated in LBNP protocols to presyncope at LA (1130m) and 5-7days following ascent to HA (3800m). Internal carotid artery (ICA) blood flow, cerebral delivery of oxygen (CDO2) through the ICA, and cerebral tissue oxygen saturation (ScO2) were determined. LBNP tolerance was similar between conditions (LA: 1276 ± 304s vs. HA: 1208 ± 306s; P = 0.58). Overall, ICA blood flow and CDO2 were elevated at HA vs. LA (P ≤ 0.01) and decreased with LBNP under both conditions (P < 0.0001), but there was no effect of altitude on ScO2 responses (P = 0.59). Thus, sustained exposure to hypobaric hypoxia did not negatively impact tolerance to simulated hemorrhage. These data demonstrate the robustness of compensatory physiological mechanisms that preserve human cerebral blood flow and oxygen delivery during sustained hypoxia, ensuring cerebral tissue metabolism and neuronal function is maintained.

Changes in regional tissue oxygen saturation values during the first week of life in stable preterm infants.

Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. Prospective observational study of infants born 30-34weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, andatseven days. Subjects were divided into gestational age(GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio(SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use whenmonitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants.

Reference Ranges for Regional Cerebral Oxygen Saturation with Masimo O3 after Birth and Differences with Other Devices.

Cerebral oximetry using near-infrared spectroscopy (NIRS) is a noninvasive optical technology widely used in neonatology. The present study aimed to define reference ranges for cerebral tissue oxygen saturation (crSO2) with a new four-wavelength NIRS device, Masimo O3 oximeter, during immediate transition after birth and compare values with those obtained previously with NIRO 200NX®. This was a prospective observational study using Masimo O3 device to measure crSO2 and regional cerebral fractional tissue oxygen extraction (cFTOE) in healthy term newborns delivered by primary cesarean section, during the 15 minutes after cord clamping. The neonates who required any medical support were excluded. The NIRS sensor was placed on the right forehead. Peripheral oxygen saturation and heart rate were continuously measured by pulse oximetry. Previous studies which established centiles for crSO2 with NIRO 200NX were used for comparison. A total of 44 newborns were included. The median crSO2 and cFTOE (interquartile range) at 2, 5, and 7 minutes was 54% (49-54), 71% (64-86), and 79% (73-84) and 0,25 (0,18-0,33), 0,19 (0,15-0,23), and 0,16 (0,12-0,21), respectively, with no further changes afterwards. The crSO2 measurements were significantly higher with Masimo O3 compared with NIRO-200NX. The present observational study presented reference ranges for crSO2 and cFTOE measured with Masimo O3 oximeter during the immediate neonatal transition. Values obtained with O3 were higher than those obtained with other oximeters. For this reason, crSO2 is device-specific so there must be known reference values for each oximeter to define therapeutic interventions based on crSO2 and assess cerebral oxygenation in clinical studies. · Masimo O3 uses four wavelengths to measure regional oxygen saturation value.. · O3 values of crSO2 and cFTOE differ with other neonatal oximeters at birth.. · Knowledge of reference range of O3 at birth is essential to guide resuscitation..

Cerebral oxygenation and perfusion kinetics monitoring of military aircrew at high G using novel fNIRS wearable system.

Real-time physiological episode (PE) detection and management in aircrew operating high-performance aircraft (HPA) is crucial for the US Military. This paper addresses the unique challenges posed by high acceleration (G-force) in HPA aircrew and explores the potential of a novel wearable functional near-infrared spectroscopy (fNIRS) system, named NIRSense Aerie, to continuously monitor cerebral oxygenation during high G-force exposure. The NIRSense Aerie system is a flight-optimized, wearable fNIRS device designed to monitor tissue oxygenation 13-20 mm below the skin's surface. The system includes an optical frontend adhered to the forehead, an electronics module behind the earcup of aircrew helmets, and a custom adhesive for secure attachment. The fNIRS optical layout incorporates near-distance, middle-distance, and far-distance infrared emitters, a photodetector, and an accelerometer for motion measurements. Data processing involves the modified Beer-Lambert law for computing relative chromophore concentration changes. A human evaluation of the NIRSense Aerie was conducted on six subjects exposed to G-forces up to +9 Gz in an Aerospace Environmental Protection Laboratory centrifuge. fNIRS data, pulse oximetry, and electrocardiography (HR) were collected to analyze cerebral and superficial tissue oxygenation kinetics during G-loading and recovery. The NIRSense Aerie successfully captured cerebral deoxygenation responses during high G-force exposure, demonstrating its potential for continuous monitoring in challenging operational environments. Pulse oximetry was compromised during G-loading, emphasizing the system's advantage in uninterrupted cerebrovascular monitoring. Significant changes in oxygenation metrics were observed across G-loading levels, with distinct responses in Deoxy-Hb and Oxy-Hb concentrations. HR increased during G-loading, reflecting physiological stress and the anti-G straining maneuver. The NIRSense Aerie shows promise for real-time monitoring of aircrew physiological responses during high G-force exposure. Despite challenges, the system provides valuable insights into cerebral oxygenation kinetics. Future developments aim for miniaturization and optimization for enhanced aircrew comfort and wearability. This technology has potential for improving anti-G straining maneuver learning and retention through real-time cerebral oxygenation feedback during centrifuge training.

Preterm infants experience a nadir in cerebral oxygenation during sleep three months after hospital discharge.

Preterm infants are at increased risk of Sudden Infant Death Syndrome (SIDS) and frequently experience short central apnoeas which can occur in isolation or a repetitive pattern (periodic breathing). We investigated the relationship between central apnoeas experienced before and over the 6 months after hospital discharge and cerebral oxygenation. Preterm infants born between 28 and 32 weeks gestational age (GA) were studied during supine daytime sleep at 32-36 weeks post menstrual age (PMA) (n = 40), 36-40 weeks PMA (n = 27), 3-months corrected age (CA) (n = 20) and 6-months CA (n = 26). Cerebral tissue oxygenation (TOI), peripheral oxygenation (SpO2) and heart rate were recorded continuously. The percentage total sleep time (%TST) spent having central apnoeas at each study and cerebral fractional oxygen extraction (SpO2-TOI/SpO2) were calculated. %TST spent with central apnoeas decreased with increasing age in both active sleep (AS) and quiet sleep (QS). TOI tended to be lower and cerebral fractional oxygen extraction higher at 3 months compared to the other studies and this reached statistical significance compared to 32-36 weeks in QS. The nadir in cerebral tissue oxygenation at 3 months of age coincides with the peak risk period for SIDS and this may contribute to increased risk in these infants.

Modeling cerebrovascular responses to assess the impact of the collateral circulation following middle cerebral artery occlusion.

An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.

Impact of Skin Pigmentation on Cerebral Regional Saturation of Oxygen Using Near-Infrared Spectroscopy: A Systematic Review.

Near-infrared spectroscopy (NIRS) is used in critical care settings to measure regional cerebral tissue oxygenation (rSo2). However, the accuracy of such measurements has been questioned in darker-skinned individuals due to the confounding effects of light absorption by melanin. In this systematic review, we aim to synthesize the available evidence on the effect of skin pigmentation on rSo2 readings. We systematically searched MEDLINE, Cochrane Database of Systematic Reviews, Embase, and Google Scholar from inception to July 1, 2023. In compliance with our PROSPERO registration (CRD42022347548), we selected articles comparing rSo2 measurements in adults either between racial groups or at different levels of skin pigmentation. Two independent reviewers conducted full-text reviews of all potentially relevant articles. We extracted data on self-reported race or level of skin pigmentation and mean rSo2 values. Of the 11,495 unique records screened, two studies (n = 7,549) met our inclusion criteria for systematic review. Sun et al (2015) yielded significantly lower rSo2 values for African Americans compared with Caucasians, whereas Stannard et al (2021) found little difference between self-reported racial groups. This discrepancy is likely because Stannard et al (2021) used a NIRS platform which specifically purports to control for the effects of melanin. Several other studies that did not meet our inclusion criteria corroborated the notion that skin pigmentation results in lower rSo2 readings. Skin pigmentation likely results in attenuated rSo2 readings. However, the magnitude of this effect may depend on the specific NIRS platform used.

Evaluation of cerebral autoregulation of oxygen by NIRS method during postnatal transition period in term and late preterm newborns without resuscitation requirement.

Pulse oximetry is commonly used to monitor arterial oxygen saturation and heart rate during the transition period and reference intervals have been determined. However, the effect of the change in arterial oxygen saturation on tissue oxygenation does not seem to be the same. So, a non-invasive method for monitoring cerebral or regional tissue oxygenation will be potentially useful for vulnerable infants. This study aims to evaluate the effectiveness of cerebral autoregulation in the first 10 min after delivery in term and late preterm newborns without resuscitation requirement. Cerebral tissue oxygen saturation was measured in the first 10 min after birth with near-infrared spectroscopy (NIRS) from the left forehead. Peripheral oxygen saturation was measured with pulse oximetry from the right hand and cerebral fractional tissue oxygen extraction was calculated. Nineteen late preterms and 20 term infants were included in the study. There was no statistically significant difference between median cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction values of late preterm and term infants (p < 0.001). There was a strong inverse relationship between cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction (p < 0.001). In late preterm infants similar to term infants, arterial oxygen saturation and cerebral tissue oxygen saturation increased with time, but inverse reduction of cerebral fractional tissue oxygen extraction showed the presence of an active autoregulation in the brain. This can be interpreted as the ability of the brain to protect itself from hypoxia by regulating oxygen uptake during normal fetal-neonatal transition process. A larger scale multi-center randomized control trial is now needed to further inform practice.

Cerebrovascular responses to a 90° tilt in healthy neonates

BackgroundTilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates.MethodsWe performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt.ResultsrcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters.ConclusionA 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations.ImpactHealthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt.We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts.No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling.

Hypercapnia increases cerebral blood flow. The effects on cerebral metabolism remain incompletely understood although studies show an oxidation of cytochrome c oxidase, Complex IV of the mitochondrial respiratory chain. Systems modelling was combined with previously published non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity with transcranial Doppler ultrasound. Data collected during 5-min hypercapnia in awake human volunteers were analysed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on mechanisms. Either a decrease in metabolic substrate supply or an increase in metabolic demand modelled the cytochrome oxidation in hypercapnia. However, only the decrease in substrate supply explained both the enzyme redox state changes and the Fick-calculated drop in brain oxygen consumption. These modelled outputs are consistent with previous reports of CO2 inhibition of mitochondrial succinate dehydrogenase and isocitrate dehydrogenase. Hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signalling pathways in health and disease.

Alleviation of Post-sepsis Ischaemia by Drag-Reducing Polymers.

Sepsis, leading to septic shock and multiple organ dysfunction syndrome, is characterised by inflammation, coagulopathy, and microvascular dysfunction, the primary cause of in-hospital mortality. Novel approaches are needed to prevent the consequences of sepsis. We showed that nanomolar concentrations of intravascular blood-soluble drag-reducing polymers (DRPs) significantly improve microvascular perfusion and tissue oxygenation and protect neurons in rat brains after traumatic brain injury and haemorrhagic shock. The aim of this work was to determine whether DRPs-enhanced perfusion could alleviate sepsis-associated microvascular dysregulation in a mouse model of lipopolysaccharide (LPS)-induced sepsis. LPS (Salmonella Thyphosa, 10mg/kg, i.v.) was administered intravenously to induce acute sepsis in C57BL/6 J mice. DRPs (final concentration 5ppm in the blood) or saline was injected i.v. (10 mice/group) 1h after LPS injection to evaluate the efficacy of haemorheological modulation of microvascular dysregulation. In-vivo two-photon laser scanning microscopy was used to monitor cerebral (parietal cortex) and peripheral (ear) microcirculation (i.v. fluorescein isothiocyanate dextran) and tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence) at a baseline and during 4h after septic shock induction. Differences between groups were determined using a two-way analysis of variance for multiple comparisons with post hoc testing. The statistical significance was set at p<0.05. LPS-induced sepsis led to microvascular dysfunction and tissue hypoxia in the brain and peripheral tissue (ear). DRPs alleviated microthrombosis formation, microvascular dysfunction, and tissue hypoxia in the brain and peripheral tissue compared to the saline control group (p<0.05). Therefore, haemorheological modulation of blood flow by DRPs effectively improves systemic and peripheral circulation, reducing microthrombosis formation, microvascular dysfunction, and tissue hypoxia that can alleviate sepsis, shock, and multiple organ dysfunction syndrome.

Chassis-based fiber-coupled opticalprobe design for reproducible quantitative diffuse optical spectroscopy measurements.

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20). The chassis-based probe design comprises a detachable fiber housing which snaps into a 3D-printed, circumferential chassis piece that is secured to the skin. To validate its reproducibility, eight measurement repetitions of cerebral tissue blood flow index (BFI), oxygen saturation (StO2), and oxy-, deoxy- and total hemoglobin concentration were acquired at the same demarcated measurement location for each pig. The probe was detached after each measurement. Of the eight measurements, four were acquired by placing the probe into a secured chassis, and four were visually aligned and manually held. We compared the absolute value and intra-subject coefficient of variation (CV) of chassis versus manual measurements. No significant differences were observed in either absolute value or CV between chassis and manual measurements (p > 0.05). However, the CV for BFI (mean ± SD: manual, 19.5% ± 9.6; chassis, 19.0% ± 10.8) was significantly higher than StO2 (manual, 5.8% ± 6.7; chassis, 6.6% ± 7.1) regardless of measurement methodology (p<0.001). The chassis-based DOS/DCS probe design facilitated rapid probe attachment/re-attachment and demonstrated comparable accuracy and reproducibility to conventional, manual alignment. In the future, this design may be adapted for clinical applications to allow for non-invasive monitoring of cerebral health during pediatric critical care.

Dependence of Cerebral Oxygenation and Task Performance on Coloured Light Exposure and Chronotype: Blue and Red Do Not Have the Same Effects on the Prefrontal Cortex.

In our previous studies, we investigated the right-left asymmetry (RLA) of cerebral tissue oxygenation (StO2) at rest in humans and the influence of the individual chronotype (i.e. individual chronobiological disposition) on StO2. The aim of the current study was to investigate (i) whether the RLA exists during a cognitive task and coloured light exposure (CLE), and (ii) how changes in StO2 induced by CLE and cognitive performance during a 2-back task are related to the subject's chronotype. 36 healthy subjects (22 female, 14 male, age 26.3 ± 5.7 years) were studied twice on two different days. They were exposed to a sequence of blue followed by red light or vice versa in a randomised crossover study design. During CLE, subjects were asked to perform a 2-back task. We measured StO2 of the right and left prefrontal cortex (PFC) as well as the right and left visual cortex with functional near-infrared spectroscopy (fNIRS). At the behavioural level, we recorded the number of correct and incorrect answers given by the subjects. The chronotype was determined with the Horne and Östberg morningness-eveningness questionnaire. (i) We found that the blue and red light caused a RLA in the PFC. For red light exposure, the 2-back performance was negatively correlated with StO2 in the right PFC (r=-0.283, p=0.016), and for blue light, exposure in the left PFC (r=-0.326, p=0.005). (ii) 83% of subjects who performed the 2-back task at their optimal time of day according to their chronotype showed increased and higher changes in StO2 (ΔStO2>1%) compared to subjects who did not exercise at their optimal time of day. (iii) No correlation was found between chronotype and 2-back task performance (red: p=0.38; blue: p=0.42). We found for the first time that blue and red lightexposure target different regions of the PFC during performance of a 2-back task, which can be explained by the approach and withdrawal model. These results illustrate that studying the subregions (i.e. right, left, and even centre) of the cortex provides a better understanding of the CLE effects in the human brain. Our study also shows that individual chronotype plays an important role in the individual changes in StO2 induced by CLE.