Cerebral Blood Flow Index Research Articles

Associations between neurological examination at term-equivalent age and cerebral hemodynamics and oxygen metabolism in infants born preterm.

Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA). Preterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA. Steeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA. In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

Fetal cardiac and neonatal cerebral hemodynamics and oxygen metabolism in transposition of the great arteries.

Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls. Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2 ) and an index of microvascular cerebral blood flow (CBFi ), along with peripheral arterial oxygen saturation (SpO2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA-VSD group. During the predischarge period, SO2 was higher in TGA-IVS than in TGA-VSD neonates, while CBFi was lower. Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease. Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients. Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test. Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.

Associations of Human Milk Oligosaccharides with Infant Brain Tissue Organization and Regional Blood Flow at 1 Month of Age.

Animal studies have shown that human milk oligosaccharides (HMOs) are important in early brain development, yet their roles have not been assessed in humans. The purpose of this study was to determine the associations of HMOs with MRI indices of tissue microstructure and regional cerebral blood flow (rCBF) in infants. Mother–infant pairs (N = 20) were recruited at 1 month postpartum. Milk was assayed for the concentrations of the HMOs 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), and 6′-sialyllactose (6′SL). Diffusion and arterial spin labeling measures were acquired using a 3.0-Tesla MRI scanner. Multiple linear regression was used to assess the voxel-wise associations of HMOs with fractional anisotropy (FA), mean diffusivity (MD), and rCBF values across the brain. After adjusting for pre-pregnancy BMI, sex, birthweight, and postmenstrual age at time of scan, a higher 2′FL concentration was associated with reduced FA, increased MD, and reduced rCBF in similar locations within the cortical mantle. Higher 3FL and 3′SL concentrations were associated with increased FA, reduced MD, and increased rCBF in similar regions within the developing white matter. The concentration of 6′SL was not associated with MRI indices. Our data reveal that fucosylated and sialylated HMOs differentially associate with indices of tissue microstructure and rCBF, suggesting specific roles for 2′FL, 3FL, and 3′SL in early brain maturation.

Cerebral hemodynamic changes to transcranial Doppler sonography in celiac disease: A pilot study.

BackgroundSonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography.Materials and methodsMontreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT).ResultsWorse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted.ConclusionThese treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement.

Ingestion of carbonated water increases middle cerebral artery blood velocity and improves mood states in resting humans exposed to ambient heat stress

Sugar-free carbonated water is consumed worldwide. The consumption of carbonated water is high in summer, when the heat loss responses of sweating and skin vasodilation are activated, and thermal perceptions (thermal sensation and comfort) and mood states are negatively modulated. However, whether ingesting carbonated water under ambient heat exposure modulates cerebral blood flow index, heat loss responses, thermal perceptions, and mood states remains to be determined. In this study, 17 healthy, habitually active, young adults (eight women) ingested 4 °C noncarbonated or carbonated water under 37 °C ambient heat-stressed resting conditions. Both drinks increased the middle cerebral artery mean blood velocity, an index of cerebral blood flow, and mean arterial pressure, with carbonated water exhibiting higher elevations than noncarbonated water (P < 0.05). However, the heart rate, sweat rate, and skin blood flow during and after drinking remained unchanged between the two conditions (P > 0.05). The thermal sensation and comfort after drinking remained unchanged between the two conditions (P > 0.05); but, a drink-induced reduction in sleepiness was higher, and drink-induced elevations in motivation and exhilaration were higher after ingesting carbonated water than those after ingesting noncarbonated water (P < 0.05). The analyses suggest that in humans under ambient heat-stressed resting conditions, ingestion of cold carbonated water increases the cerebral blood flow index, blood pressure, motivation, and exhilaration, whereas it decreases sleepiness relative to ingestion of noncarbonated cold water. However, ingestion of cold carbonated water fails to modulate thermoregulatory responses and thermal perception as opposed to noncarbonated cold water.

Intraoperative Cerebral Hemodynamic Monitoring during Carotid Endarterectomy via Diffuse Correlation Spectroscopy and Near-Infrared Spectroscopy.

Objective: This pilot study aims to show the feasibility of noninvasive and real-time cerebral hemodynamic monitoring during carotid endarterectomy (CEA) via diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). Methods: Cerebral blood flow index (CBFi) was measured unilaterally in seven patients and bilaterally in seventeen patients via DCS. In fourteen patients, hemoglobin oxygenation changes were measured bilaterally and simultaneously via NIRS. Cerebral autoregulation (CAR) and cerebrovascular resistance (CVR) were estimated using CBFi and arterial blood pressure data. Further, compensatory responses to the ipsilateral hemisphere were investigated at different contralateral stenosis levels. Results: Clamping of carotid arteries caused a sharp increase of CVR (~70%) and a marked decrease of ipsilateral CBFi (57%). From the initial drop, we observed partial recovery in CBFi, an increase of blood volume, and a reduction in CVR in the ipsilateral hemisphere. There were no significant changes in compensatory responses between different contralateral stenosis levels as CAR was intact in both hemispheres throughout the CEA phase. A comparison between hemispheric CBFi showed lower ipsilateral levels during the CEA and post-CEA phases (p < 0.001, 0.03). Conclusion: DCS alone or combined with NIRS is a useful monitoring technique for real-time assessment of cerebral hemodynamic changes and allows individualized strategies to improve cerebral perfusion during CEA by identifying different hemodynamic metrics.

A Bayesian estimation method for cerebral blood flow measurement by area-detector CT perfusion imaging.

Bayesian estimation with advanced noise reduction (BEANR) in CT perfusion (CTP) could deliver more reliable cerebral blood flow (CBF) measurements than the commonly used reformulated singular value decomposition (rSVD). We compared the efficacy of CBF measurement by CTP using BEANR and rSVD, evaluating both relative to N-isopropyl-p-[(123) I]- iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT) as a reference standard, in patients with cerebrovascular disease. Thirty-one patients with suspected cerebrovascular disease underwent both CTP on a 320 detector-row CT system and SPECT. We applied rSVD and BEANR in the ischemic and contralateral regions to create CBF maps and calculate CBF ratios from the ischemic side to the healthy contralateral side (CBF index). The analysis involved comparing the CBF index between CTP methods and SPECT using Pearson's correlation and limits of agreement determined with Bland-Altman analyses, before comparing the mean difference in the CBF index between each CTP method and SPECT using the Wilcoxon matched pairs signed-rank test. The CBF indices of BEANR and 123I-IMP SPECT were significantly and positively correlated (r = 0.55, p < 0.0001), but there was no significant correlation between the rSVD method and SPECT (r = 0.15, p > 0.05). BEANR produced smaller limits of agreement for CBF than rSVD. The mean difference in the CBF index between BEANR and SPECT differed significantly from that between rSVD and SPECT (p < 0.001). BEANR has a better potential utility for CBF measurement in CTP than rSVD compared to SPECT in patients with cerebrovascular disease.

Quantifying the Cerebral Hemometabolic Response to Blood Transfusion in Pediatric Sickle Cell Disease With Diffuse Optical Spectroscopies.

Red blood cell transfusions are common in patients with sickle cell disease who are at increased risk of stroke. Unfortunately, transfusion thresholds needed to sufficiently dilute sickle red blood cells and adequately restore oxygen delivery to the brain are not well defined. Previous work has shown that transfusion is associated with a reduction in oxygen extraction fraction and cerebral blood flow, both of which are abnormally increased in sickle patients. These reductions are thought to alleviate hemometabolic stress by improving the brain's ability to respond to increased metabolic demand, thereby reducing susceptibility to ischemic injury. Monitoring the cerebral hemometabolic response to transfusion may enable individualized management of transfusion thresholds. Diffuse optical spectroscopies may present a low-cost, non-invasive means to monitor this response. In this study, children with SCD undergoing chronic transfusion therapy were recruited. Diffuse optical spectroscopies (namely, diffuse correlation spectroscopy combined with frequency domain near-infrared spectroscopy) were used to quantify oxygen extraction fraction (OEF), cerebral blood volume (CBV), an index of cerebral blood flow (CBFi), and an index of cerebral oxygen metabolism (CMRO2i) in the frontal cortex immediately before and after transfusion. A subset of patients receiving regular monthly transfusions were measured during a subsequent transfusion. Data was captured from 35 transfusions in 23 patients. Transfusion increased median blood hemoglobin levels (Hb) from 9.1 to 11.7 g/dL (p < 0.001) and decreased median sickle hemoglobin (HbS) from 30.9 to 21.7% (p < 0.001). Transfusion decreased OEF by median 5.9% (p < 0.001), CBFi by median 21.2% (p = 0.020), and CBV by median 18.2% (p < 0.001). CMRO2i did not statistically change from pre-transfusion levels (p > 0.05). Multivariable analysis revealed varying degrees of associations between outcomes (i.e., OEF, CBFi, CBV, and CMRO2i), Hb, and demographics. OEF, CBFi, and CBV were all negatively associated with Hb, while CMRO2i was only associated with age. These results demonstrate that diffuse optical spectroscopies are sensitive to the expected decreases of oxygen extraction, blood flow, and blood volume after transfusion. Diffuse optical spectroscopies may be a promising bedside tool for real-time monitoring and goal-directed therapy to reduce stroke risk for sickle cell disease.

Influence of source-detector separation on diffuse correlation spectroscopy measurements of cerebral blood flow with a multilayered analytical model.

.Significance: Diffuse correlation spectroscopy (DCS) is an emerging noninvasive optical technology for bedside monitoring of cerebral blood flow. However, extracerebral hemodynamics can significantly influence DCS estimations of cerebral perfusion. Advanced analytical models can be used to remove the contribution of extracerebral hemodynamics; however, these models are highly sensitive to measurement noise. There is a need for an empirical determination of the optimal source–detector separation(s) (SDS) that improves the accuracy and reduces sensitivity to noise in the estimation of cerebral blood flow with these models.Aim: To determine the influence of SDS on solution uniqueness, measurement accuracy, and sensitivity to inaccuracies in model parameters when using the three-layer model to estimate cerebral blood flow with DCS.Approach: We performed a series of in silico simulations on samples spanning a wide range of physiologically-relevant layer optical properties, thicknesses, and flow. Data were simulated at SDS ranging from 0.5 to 3.0 cm using the three-layer solution to the correlation diffusion equation (with and without noise added) and using three-layer slab Monte Carlo simulations. We quantified the influence of SDS on uniqueness, accuracy, and sensitivity to inaccuracies in model parameters using the three-layer inverse model.Results: Two SDS are required to ensure a unique solution of cerebral blood flow index (CBFi). Combinations of 0.5/1.0/1.5 and 2.5 cm provide the optimal choice for balancing the depth penetration with signal-to-noise ratio to minimize the error in CBFi across a wide range of samples with varying optical properties, thicknesses, and dynamics.Conclusions: These results suggest that the choice of SDS is critical for minimizing the estimated error of cerebral blood flow when using the three-layer model to analyze DCS data.

Some aspects of cardio-cerebral relationship in surgical patients with multifocal atherosclerosis and heart failure

Relevance . The level of cerebral perfusion in patients with multifocal atherosclerosis depends not only on the restriction of blood flow through the carotid arteries, but also on the degree of myocardial changes. Goal of investigation. Determine the presence of a relationship between the indices of regional cerebral blood flow according to SPECT data and echocardiographic parameters of cardiac activity and analyze the mechanism of their relationship. Material and methods . We examined 22 patients (18 men and 4 women aged 64 ± 6.5 years) with signs of chronic heart failure and multifocal atherosclerosis with the involvement of carotid and coronary arteries, who underwent simultaneous surgery. All patients underwent echocardiographic examination of the heart and SPECT of the brain. Results . Moderate direct correlations were revealed between the indices of regional cerebral blood flow (CBF) and ejection fraction (p = 0.009307), SV/EDV (p = 0.012431); moderate inverse correlations between the indices of CBF and SV (p = 0.002913), EDV (p = 0.031737), ESV (p = 0.016483), ESV/EDV (p = 0.010645), ESV/SV (p = 0.007255). In the postoperative period, a moderate direct correlation was found between indicators of cognitive status (MMSE) and indicators of cerebral perfusion in the right occipital, parietal and frontal lobes (p = 0.021162, R = 0.511475). Conclusion . The echocardiographic parameters we studied in patients with chronic heart failure correlate with indicators of regional cerebral blood flow, and this relationship is more pronounced not in the ejection fraction, but is traced between the parameters of the end diastolic volume, end systolic volume and their ratio according to the principle of the golden ratio. The data obtained on the perfusion of the brain by the SPECT method are associated with indicators of cardiac activity and reflect the severity of chronic heart failure.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n=11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n=9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n=11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

Cerebrovascular Carbon Dioxide Reactivity with Hyperoxia and Hypoxia in Humans with Treated Hypertension

Hypertension increases the risk of cerebrovascular diseases such as stroke and dementia, but the underlying mechanisms are currently unclear. While chronic hypertension can lead to anatomical and functional adaptations within the cerebral circulation, its effect on cerebral blood flow (CBF) control remains poorly understood. We tested the hypothesis that the CBF responses to CO2 with either high or low oxygen levels are impaired in treated hypertensive patients compared to normotensive aged‐matched controls.In 14 treated hypertensive patients (age: 68±5 years, mean±SD) and 8 normotensive age‐matched controls (age: 66±6 years), we assessed cardiorespiratory and cerebrovascular variables at rest, during voluntary hyperventilation (partial pressure of end‐tidal CO2 [PETCO2] ~25 mmHg), and hyperoxic and hypoxic rebreathing. Using transcranial Doppler ultrasound and finger photoplethysmography, we measured beat‐to‐beat middle cerebral artery blood velocity (MCAv: index of CBF) and BP, respectively, while PETCO2 was assessed using a gas analyzer. Linear regression was used to determine the MCAv‐CO2 slope (i.e., cerebrovascular CO2 reactivity).At rest, mean BP was higher in the hypertensive patients (108±9 mmHg) compared to normotensive controls (93±10 mmHg, p=0.001), while MCAv (46.8±11.4 vs. 53.3±10.4 cm/s) and PETCO2 (41±4 vs. 42±3 mmHg) were not different between groups (p&lt;0.05). Hyperventilation‐induced hypocapnia elicited similar reductions in MCAv in the hypertensive and normotensive groups (Δ14.8±4.7 vs. Δ16.5±5.7 cm/s, p=0.484). Similarly, the MCAv‐CO2slope was not different between the hypertensive and normotensive groups during either hyperoxic rebreathing (1.53±1.05 vs. 1.98±0.56 cm/s/mmHg, p=0.320) or hypoxic rebreathing (1.94±1.04 vs. 2.21±1.13 cm/s/mmHg, p=0.815).These preliminary findings indicate that in treated hypertensive patients, the MCAv responses to hypocapnia, and hypercapnia administrated with either high or low oxygen levels, do not differ from that observed in age‐matched normotensive controls.

Assessment by Multi‐Distance Hyperspectral NIRS of Changes in the Oxidation State of Cytochrome C Oxidase (oxCCO) to Carotid Artery Compressions

IntroductionThe occlusion of the common carotid artery (CCA) during carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia due to inadequate collateral blood flow1. By monitoring tissue oxygen saturation (StO2), near‐infrared spectroscopy (NIRS) is frequently employed during CEA2 to determine sufficient oxygen delivery. However, StO2 is only a proxy of oxygen metabolism and an unreliable marker of ischemic injury. In contrast, cytochrome c oxidase (oxCCO) is an enzyme in the mitochondrial electron transport chain and therefore a specific marker of aerobic metabolism3. Thus, the aim of this study was to assess the ability of a multi‐distance hyperspectral (hs) NIRS to monitor changes in StO2 and oxCCO during CCA compressions in healthy participants. We hypothesized that changes in oxCCO concentration would be greater in the brain (i.e., long source‐detector distance, SDD) than in the extracerebral tissue (i.e., short SDD), and this difference would be larger than that of StO2.MethodsWe modified an in‐house built hsNIRS4 to include a second channel for acquiring data at two SDD (1 and 3 cm) to detect potential changes in the extracerebral tissue. Data from 10 young, healthy participants was acquired continuously during one 30‐second unilateral digital CCA compression, performed ipsilateral to the location of the optic probes. In addition, cerebral blood flow index was determined using diffuse correlation spectroscopy and mean arterial blood pressure by finger photoplethysmography.ResultsDuring CCA compression, the change in oxCCO at 3 cm vs. 1 cm (0.4 ± 0.3 µM vs. 0.06 ± 0.1 µM, p = 0.027) was approximately 50% greater than the change in StO2 at 3 cm vs. 1cm (‐4.0 ± 2.2% vs. 1.2 ± 0.7% p = 0.007). The corresponding decrease in cerebral blood flow was 57 ± 14% (p &lt; 0.001 vs. baseline). Mean arterial blood pressure increased 4 ± 1 mmHg (p &lt; 0.001 vs. baseline).DiscussionA larger difference between the two distances was observed for oxCCO than StO2, likely due to the greater concentration of mitochondria in the brain compared to extracerebral tissues. Collecting multi‐distance hsNIRS demonstrated the enhanced sensitivity of oxCCO to the brain. Lastly, this study demonstrates the utility of momentary unilateral CCA compressions as a fast, easy, and strong perturbation for transiently altering cerebral inflow and metabolism.References(1) Aceto, Eur. J. Anestesiol.(2020); (2) Yu, Cochrane Database Syst. Rev.(2014); (3) Bale, J. Biomed. Opt. (2020); (4) Rajaram, Brain Sci (2020).

Cortical Spreading Depolarization, Blood Flow, and Cognitive Outcomes in a Closed Head Injury Mouse Model of Traumatic Brain Injury.

Cortical spreading depolarizations (CSDs) are associated with worse outcomes in many forms of acute brain injury, including traumatic brain injury (TBI). Animal models could be helpful in developing new therapies or biomarkers to improve outcomes in survivors of TBI. Recently, investigators have observed CSDs in murine models of mild closed head injury (CHI). We designed the currently study to determine additional experimental conditions under which CSDs can be observed, from mild to relatively more severe TBI. Adult male C57Bl/6J mice (8-14weeks old) were anesthetized with isoflurane and subjected to CHI with an 81-g weight drop from 152 or 183cm. CSDs were detected with minimally invasive visible light optical intrinsic signal imaging. Cerebral blood flow index (CBFi) was measured in the 152-cm drop height cohort using diffuse correlation spectroscopy at baseline before and 4min after CHI. Cognitive outcomes were assessed at 152- and 183-cm drop heights for the Morris water maze hidden platform, probe, and visible platform tests. CSDs occurred in 43% (n = 12 of 28) of 152-cm and 58% (n = 15 of 26) of 183-cm drop height CHI mice (p = 0.28). A lower baseline preinjury CBFi was associated with development of CSDs in CHI mice (1.50 ± 0.07 × 10-7 CHI without CSD [CSD-] vs. 1.17 ± 0.04 × 10-7 CHI with CSD [CSD+], p = 0.0001). Furthermore, in CHI mice that developed CSDs, the ratio of post-CHI to pre-CHI CBFi was lower in the hemisphere ipsilateral to a CSD compared with non-CSD hemispheres (0.19 ± 0.07 less in the CSD hemisphere, p = 0.028). At a 152-cm drop height, there were no detectable differences between sham injured (n = 10), CHI CSD+ (n = 12), and CHI CSD- (n = 16) mice on Morris water maze testing at 4weeks. At a 183-cm drop height, CHI CSD+ mice had worse performance on the hidden platform test at 1-2weeks versus sham mice (n = 15 CHI CSD+, n = 9 sham, p = 0.045), but there was no appreciable differences compared with CHI CSD- mice (n = 11 CHI CSD-). The data suggest that a lower baseline cerebral blood flow prior to injury may contribute to the occurrence of a CSD. Furthermore, a CSD at the time of injury can be associated with worse cognitive outcome under the appropriate experimental conditions in a mouse CHI model of TBI.

Aerobic exercise training in older men and women-Cerebrovascular responses to submaximal exercise: Results from the Brain in Motion study.

Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age‐related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6‐month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO2max and 65 W), intensities that have been shown to be comparable to activities of daily life. Two hundred three low‐active healthy men and women enrolled in the Brain in Motion study, completed a 6‐month exercise intervention and underwent submaximal and maximal tests pre‐/post‐intervention. The intervention improved the gas exchange threshold and maximal oxygen consumption (VO2max), with no change in heart rate at VO2max, during the treadmill VO2max test. Heart rate and CVRi decreased from pre‐intervention values during both relative (40% VO2max) and absolute (65 W) submaximal exercise tests. Blood flow velocity in the middle cerebral artery and CVCi increased post‐intervention during 40% VO2max and 65 W. Changes in mean arterial pressure were found only during the absolute component (65 W). Our study demonstrates that aerobic exercise improves not only cardiorespiratory indices but also cerebrovascular function at submaximal workloads which may help to mitigate age‐related declines in everyday life. Investigation of the mechanisms underlying the decline in cardiovascular and cerebrovascular capacity with aging has important implications for the maintenance of health and continued independence of older adults.

Validity of transcranial Doppler ultrasonography-determined dynamic cerebral autoregulation estimated using transfer function analysis.

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15mmHg and - 50mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.

Value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy in burn patients with sepsis

Value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy in burn patients with sepsis

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

The Clamping of End-Tidal Carbon Dioxide Does Not Influence Cognitive Function Performance During Moderate Hyperthermia With or Without Skin Temperature Manipulation.

Increases in body temperature from heat stress (i.e., hyperthermia) generally impairs cognitive function across a range of domains and complexities, but the relative contribution from skin versus core temperature changes remains unclear. Hyperthermia also elicits a hyperventilatory response that decreases the partial pressure of end-tidal carbon dioxide (PetCO2) and subsequently cerebral blood flow that may influence cognitive function. We studied the role of skin and core temperature along with PetCO2 on cognitive function across a range of domains. Eleven males completed a randomized, single-blinded protocol consisting of poikilocapnia (POIKI, no PetCO2 control) or isocapnia (ISO, PetCO2 maintained at baseline levels) during passive heating using a water-perfused suit (water temperature ~ 49°C) while middle cerebral artery velocity (MCAv) was measured continuously as an index of cerebral blood flow. Cognitive testing was completed at baseline, neutral core-hot skin (37.0 ± 0.2°C-37.4 ± 0.3°C), hot core-hot skin (38.6 ± 0.3°C-38.7 ± 0.2°C), and hot core-cooled skin (38.5 ± 0.3°C-34.7 ± 0.6°C). The cognitive test battery consisted of a detection task (psychomotor processing), 2-back task (working memory), set-shifting and Groton Maze Learning Task (executive function). At hot core-hot skin, poikilocapnia led to significant (both p < 0.05) decreases in PetCO2 (∆−21%) and MCAv (∆−26%) from baseline, while isocapnia clamped PetCO2 (∆ + 4% from baseline) leading to a significantly (p = 0.023) higher MCAv (∆−18% from baseline) compared to poikilocapnia. There were no significant differences in errors made on any task (all p > 0.05) irrespective of skin temperature or PetCO2 manipulation. We conclude that neither skin temperature nor PetCO2 maintenance significantly alter cognitive function during passive hyperthermia.