Variations In Cerebral Blood Flow Research Articles

Detection of Brain Hypoxia Based on Noninvasive Optical Monitoring of Cerebral Blood Flow with Diffuse Correlation Spectroscopy.

Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO2) monitors. Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8h of daily monitoring. Brain PbO2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO2 below 19mmHg for more than 6min from baseline (PbO2 > 21mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21mmHg) and "low" (< 19mmHg) PbO2. Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension. Seven patients were enrolled and monitored for a total of 17days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO2, we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO2 epochs (AUC 0.876). The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

A Wearable Fiberless Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Mice.

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultra-small low-power CMOS camera as a 2D detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements (R2 ≥ 0.80, p < 10-5). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source-detector configuration allows for varied probing depths up to ~8 mm, which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome.

Prolonged, disabling fatigue is the hallmark of chronic fatigue syndrome (CFS). Previous neuroimaging studies have provided evidence for nervous system involvement in CFS etiology, including perturbations in brain structure/function. In this arterial spin labeling (ASL) MRI study, we examined variability in cerebral blood flow (CBFV) and heart rate (HRV) in 28 women: 14 with CFS and 14 healthy controls. We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals. Our results provided support for these hypotheses. Although no group differences in CBFV or HRV were detected, greater CBFV and more HRV power were both associated with lower fatigue symptom severity in individuals with CFS. Exploratory statistical analyses suggested that protective effects of high CBFV were greatest in individuals with low HRV. We also found novel evidence of bidirectional association between the very high frequency (VHF) band of HRV and CBFV. Taken together, the results of this study suggest that CBFV and HRV are potentially important measures of adaptive capacity in chronic illnesses like CFS. Future studies should address these measures as potential therapeutic targets to improve outcomes and reduce symptom severity in individuals with CFS.

Baseline NAWM structural integrity and CBF predict periventricular WMH expansion over time.

We aimed to describe and compare baseline cerebral blood flow (CBF) and microstructural characteristics of normal-appearing white matter (NAWM) within the vulnerable periventricular white matter hyperintensity (PVWMH) penumbra region in predicting white matter hyperintensity (WMH) growth over time. Fifty-two patients, aged 82.8 years, underwent serial brain MRI, including pulsed arterial spin labeling and diffusion tensor imaging (DTI). New WMH and persistent NAWM voxels in relation to WMH penumbra at follow-up were identified. Mean baseline CBF and DTI variables of the new WMH and persistent NAWM voxels were computed. Univariate analyses with paired t tests were performed. Generalized estimating equation analyses were used to compare the relationships of baseline CBF, and structural penumbras with WMH growth, controlling for confounders. Low baseline CBF and fractional anisotropy, and high mean diffusivity (MD), were independently associated with new PVWMH voxels, with MD being the best predictor of WMH growth. A separate model demonstrated that radial diffusivity had the strongest relationship with WMH growth compared with CBF and axial diffusivity. CBF and DTI measures independently predict WMH growth over time. DTI is a more sensitive predictor of WMH growth than CBF, with WMH progression likely due to demyelinating injury secondary to low perfusion. Findings support the use of MD as a sensitive marker of NAWM vulnerability in future trials aimed at preserving WM integrity.

O4.3. INCREASED CEREBRAL BLOOD FLOW AFTER SINGLE DOSE OF ANTIPSYCHOTICS IN HEALTHY SUBJECTS DEPENDS ON DOPAMINE D2 RECEPTOR DENSITY PROFILES EVALUATED WITH PET AND MRNA EXPRESSION DATA.

BackgroundPrevious studies measuring cerebral blood flow (CBF) with magnetic resonance sequences like Arterial Spin Labelling (ASL) showed that patients with schizophrenia (SCZ) have increased CBF in basal ganglia and reduced blood flow in cortical areas like the prefrontal cortex. It is still not clear whether these abnormalities are related to antipsychotic treatment or rather they reflect a disease trait independent from medication. Interestingly, administration of single dose of antipsychotics in healthy volunteers produce marked functional effects that are in the same region reported as altered in SCZ. These effects are thought to depend on dopamine D2 receptor (D2R) blockade, although their relationship with antipsychotic pharmacodynamics has not been fully established yet. In fact, the haemodynamic nature of CBF measures makes difficult to interpret drug effects in terms of altered neurotransmission function. Here, we tested whether CBF changes induced by different antipsychotics mirror receptor distribution profiles of D2R. We evaluated the correlation of CBF variation with receptor density as measured with PET and brain mRNA expression extracted from the Allen Human Brain Atlas (ABA).MethodsForty-two healthy male subjects were enrolled in a double blind, randomized, placebo-controlled, crossover study. Participants were randomized in two equal parallel groups to receive a single dose of antipsychotic/placebo in three separate sessions. In Group 1 placebo, olanzapine 7.5mg (OLA) or haloperidol 3mg (HAL) were administered before the MRI scan. In Group 2 participants received placebo, 0.5mg (lowRIS) or 2mg (highRIS) of risperidone. Regional CBF was assessed with pseudo-continuous ASL (pCASL) sequence. For each antipsychotic, a paired T-test was performed in SPM12 with global CBF values as covariate of no interest.A template image of dopamine D2 receptor density was derived from 6 PET scans in healthy volunteers using the high affinity D2/D3 antagonist ligand [18F]-Fallypride. Brain mRNA expression values for DRD2 gene (coding for D2R) were extracted from the ABA dataset by using the MENGA toolbox. CBF contrast images and the [18F]Fallypride BPND template were segmented into 83 ROIs by using the Desikan-Killiany Atlas. The regional changes in CBF against placebo (∆CBF) were compared with regional BPND values and gene expression maps using multivariate correlations.ResultsFor all antipsychotics, CBF changes in each ROI were directly proportional to [18F]Fallypride non displaceable binding potential (BPND) values (OLA R2= 0.24, HAL R2= 0.61, lowRIS R2= 0.54, highRIS R2= 0.52, all p<0.001) and DRD2 mRNA expression levels (OLA R2= 0.04, HAL R2= 0.15, lowRIS R2= 0.19, highRIS R2= 0.20, all chance likelihood <2%).DiscussionIn the present study, we were able to show that the CBF increase induced by antipsychotic is directly proportional to D2R concentration in the brain, as indexed by PET BPND maps and mRNA expression levels. Interestingly, the association strength between ∆CBF and brain receptor distribution profiles mirrored differential D2R affinity between the tested drugs. Overall, these results indicate that CBF increases after administration of a single dose of antipsychotics actually reflect known pharmacodynamics profile of these compounds. In addition, these results further reinforce previous evidence suggesting the role of D2R blockade as a mechanism behind increased CBF induced by antipsychotics. Finally, CBF is ultimately a functional marker and this work is important in bridging the considerable gap between the pharmacokinetic and pharmacodynamic effects of compounds with unclear brain functional effects like antipsychotics.

Brain tissue pulsatility mediates cognitive and electrophysiological changes in normal aging: Evidence from ultrasound tissue pulsatility imaging (TPI)

Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm. To assess vascular health, we used an innovative measure of the pulsatility of deep brain tissue, due to variations in cerebral blood flow over the cardiac cycle. Results showed (1) a classical effect of age on fluid neurocognitive measures (inhibition, fluid intelligence, magnitude and latency of the P3b) but not on crystallized measures, (2) that brain pulsatility decreases with advancing age, (3) that brain pulsatility is positively correlated with fluid neurocognitive measures and (4) that brain pulsatility strongly mediated the age-related variance in cognitive performance and the magnitude of the P3b component. The mediating role of the brain pulsatility in age-related effect on neurocognitive measures supports the vascular hypothesis of cognitive aging.

Carotid Doppler sonography: additional tool to assess hemodynamic improvement after transcatheter aortic valve implantation.

The aim of our study was to assess the arterial cerebral blood flow variations in patients with aortic valve stenosis, immediately after the transcatheter aortic valve implantation (TAVI). The study population includes 62 consecutive patients who underwent TAVI for aortic valve stenosis (95%) and sugical bioprosthesis degeneration (5%). Carotid Doppler examination was performed recording blood flow, systolic peak velocity, time average mean velocity and mean acceleration time at baseline, after balloon aortic valvuloplasty, and within 10 min after the device release. A significant improvement of blood flow was recorded at the end of the procedure (from 315.05 ± 141.72 to 538.67 ± 277.46 ml/min; P < 0.00001). The systolic peak velocity and the time average mean velocity increased from 52.27 ± 14.29 to 78.89 ± 20.48 cm/s (P < 0.00001) and from 12.24 ± 4.74 to 21.21 ± 9 cm/s (P < 0.00001), respectively. Consensually, the mean acceleration time decreased from 0.22 ± 0.02 to 0.03 ± 0.02 s (P < 0.00001) after the procedure. Monitoring of Doppler measurements may be a useful and noninvasive method to assess acutely the improvement of hemodynamic flow after TAVI, specifically for the cerebral district.

Perfusion computed tomographic measurements of cerebral blood flow variables in live Holstein calves.

OBJECTIVE To measure cerebral blood flow (CBF) and cerebral blood volume (CBV) by means of perfusion CT in clinically normal Holstein calves. ANIMALS 9 Holstein calves. PROCEDURES Each of the 9 calves (mean age, 20.2 days) was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm. RESULTS Among the 9 calves, the mean ± SD CBF in the cerebral cortex, white matter, and thalamus was 44.3 ± 10.3 mL/100 g/min, 36.1 ± 7.5 mL/100 g/min, and 40.3 ± 7.5 mL/100 g/min, respectively. The CBF in white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex, white matter, and thalamus was 6.8 ± 1.0 mL/100 g, 5.2 ± 1.0 mL/100 g, and 5.7 ± 0.7 mL/100 g, respectively. The CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus. CONCLUSIONS AND CLINICAL RELEVANCE Measurement of CBF and CBV in clinically normal calves by means of perfusion CT was feasible. The data obtained may be useful as baseline values for use in future research or for comparison with findings from calves with CNS diseases. Investigations to determine the lower limit of blood flow at which brain function can still be restored are warranted.

Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study

Pain, fatigue, and concentration difficulties are typical features of chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms are still unknown, but available evidence suggests an important role for impaired pain modulation. As evidence also suggests that pain modulation is related to cardiovascular mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart rate variability (HRV) are altered in these patients. We aimed to investigate the role of the cardiovascular system in pain modulation and symptoms of CFS; the response of CBF and HRV to physical stress and their relation to the change in temporal summation (TS) of pressure pain and self-reported symptoms was evaluated. A controlled, randomized cross-over trial. University Hospital Brussels. Twenty CFS patients and 20 sedentary healthy controls were included in this study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial Doppler), and HRV (using finger plethysmography) was examined during physical and emotional stress (to control for potential bias), as well as their association mutually and with self-reported symptoms of pain, fatigue, and concentrations difficulties. There was no significant interaction or group (F-values ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV and CBF did change during physical exercise, but the changes did not differ between patients and controls. While pain scores during TS at the trapezius site reduced in the control group after the physical exercise protocol (P = .037), they did not change in the CFS group (P = .108), suggesting impaired pain modulation. There were no significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values of correlation analyses > .01). Although effect sizes were medium to large, the study sample was relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild exercise was able to provoke endogenous pain modulation in the control group, which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are more applicable to daily physical activities in CFS patients than vigorous exercises. These results seem to refute the previously suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters appear not to explain pain before, during, and following exercise. Chronic pain, physical exercise, emotional stress, pain modulation, cardiovascular systems, temporal summation, pain pressure thresholds, transcranial Doppler, plethysmography.

Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease.

There is emerging evidence suggesting that Alzheimer's disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s−1 between the two cases.

Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic model

BackgroundDespite significant advancements of optical imaging techniques for mapping hemodynamics in small animal models, it remains challenging to combine imaging with spatially resolved electrical recording of individual neurons especially for longitudinal studies. This is largely due to the strong invasiveness to the living brain from the penetrating electrodes and their limited compatibility with longitudinal imaging. New methodWe implant arrays of ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at the brain surface and intracortically, which maintain great tissue compatibility chronically. By mounting a cranial window atop of the NET arrays that allows for chronic optical access, we establish a multimodal platform that combines spatially resolved electrical recording of neural activity and laser speckle contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies. ResultsWe induce peri-infarct depolarizations (PIDs) by targeted photothrombosis, and show the ability to detect its occurrence and propagation through spatiotemporal variations in both extracellular potentials and CBF. We also demonstrate chronic tracking of single-unit neural activity and CBF over days after photothrombosis, from which we observe reperfusion and increased firing rates. Comparison with existing method(s)This multimodal platform enables simultaneous mapping of neural activity and hemodynamic parameters at the microscale for quantitative, longitudinal comparisons with minimal perturbation to the baseline neurophysiology. ConclusionThe ability to spatiotemporally resolve and chronically track CBF and neural electrical activity in the same living brain region has broad applications for studying the interplay between neural and hemodynamic responses in health and in cerebrovascular and neurological pathologies.

The contribution of modifiable risk factors to the formation of cardiovascular remodelling and vegetative balance in patients with essential hypertension

Objective. The aim of this study is to determine the influence of individual modifiable risk factors (RF) and their combination on the structural and functional alteration of heart and blood vessels, the state of vegetative balance of the heart rhythm parameters in patients with essential hypertension stage II. Materials and methods. The examined patients with essential hypertension (EH) stage II with the presence of one RF were divided into three groups: the first group included 69 patients with hypercholesterolemia (HCE), the second group consisted of 30 patients with the status of smoker (SS) and the third comprised 82 patients with overweight (OW). The control group included 10 patients with EH without RF. All patients were subjected to the evaluation of general physical examinations, calculation of body mass index, determination of serum total colesterol (TC) level, ECG Holter monitoring with analysis of heart rate variability, ambulatory blood pressure monitoring, echocardiography and duplex pulsed wave dopplerography of extracranial vessels. Results . Patients with EH with any one RF did not differ from patients with EH without RF and among themselves in parameters of office blood pressure, as well as on parameters of ABPM. The mean diastolic blood pressure per day and the time index were significantly higher in patients with EH with any RF compared to EH patients without RF. Patients with EH with OW and patients with EH who smoke did not differ in the TC level but both groups had a significantly higher level of TC compared to patients in the control group. The addition of any single RF in patients with EH is associated with an increase in the size of left atrium, left ventricular myocardial mass index mainly due to thickening of the interventricular septum, diastolic dysfunction of the left ventricle. The addition of any RF in the examined patients is accompanied by a tendency to decrease in blood flow in all vessels basins, but mainly in the common carotid arteries. The highest LF/HF ratio was in patients with EH who have SS, that is, the presence of this risk factor is associated with maximum activation of the sympathetic link of the autonomic nervous system in patients with EH. Patients with EH who have two risk factors also did not differ in the majority of anthropometric parameters, all data of office blood pressure, ambulatory blood pressure monitoring, structural and functional alteration of the heart, cerebral blood flow and heart rate variability. Conclusions . The presence of any risk factor in EH patients has an unidirectional negative effect on the structural, geometric and functional alteration of the heart, is associated with a tendency to reduce blood flow in all of extra- and intracranial vessels. Patients with EH who smoke are characterized by sympathetic link of autonomic nervous system activation. Patients with EH and different combinations of two risk factors do not differ among themselves by the majority of anthropometric parameters, values of office BP, ABPM, structural and functional alteration of the heart, cerebral blood flow and heart rate variability.

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO2 to maintain constant CMRO2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc.

Exercise Training Increases Parietal Lobe Cerebral Blood Flow in Chronic Stroke: An Observational Study.

Exercise is increasingly recommended as an essential component of stroke rehabilitation, yet uncertainty remains with respect to its direct effect on the cerebral vasculature. The current study first demonstrated the repeatability of pseudo-continuous arterial spin labeling (ASL) magnetic resonance imaging (MRI) in older adults with stroke, and then investigated the change in cerebrovascular function following a 6-month cardiovascular rehabilitation program. In the repeatability study, 12 participants at least 3 months post-stroke underwent two ASL imaging scans 1 month apart. In the prospective observational study, eight individuals underwent ASL imaging and aerobic fitness testing before and after a 6-month cardiovascular rehabilitation program. Cerebral blood flow (CBF) and the spatial coefficient of variation of CBF (sCoV) were quantified to characterize tissue-level perfusion and large cerebral artery transit time properties, respectively. In repeat scanning, intraclass correlation (ICC) indicated moderate test-retest reliability for global gray matter CBF (ICC = 0.73) and excellent reliability for sCoV (ICC = 0.94). In the observational study, gray matter CBF increased after training (baseline: 40 ± 13 vs. 6-month: 46 ± 12 ml·100 g−1·min−1, P = 0.036). The greatest change occurred in the parietal lobe (+18 ± 12%). Gray matter sCoV, however, did not change following training (P = 0.31). This study provides preliminary evidence that exercise-based rehabilitation in chronic stroke enhances tissue-level perfusion, without changing the relative hemodynamic properties of the large cerebral arteries.

Respiration-related cerebral blood flow variability increases during control-mode non-invasive ventilation in normovolemia and hypovolemia.

Increased variability in cerebral blood flow (CBF) predisposes to adverse cerebrovascular events. Oscillations in arterial blood pressure and PaCO2 induce CBF variability. Less is known about how heart rate (HR) variability affects CBF. We experimentally reduced respiration-induced HR variability in healthy subjects, hypothesizing that CBF variability would increase. Internal carotid artery (ICA) blood velocity was recorded by Doppler ultrasound in ten healthy subjects during baseline, control-mode, non-invasive mechanical ventilation (NIV), i.e., with fixed respiratory rate, hypovolemia induced by lower body negative pressure, and combinations of these. ICA beat volume (ICABV) and ICA blood flow (ICABF) were calculated. HR, mean arterial blood pressure (MAP), respiratory frequency (RF), and end-tidal CO2 were recorded. Integrals of power spectra at each subject's RF±0.03Hz were used to measure variability. Phase angle/coherence measured coupling between cardiovascular variables. Control-mode NIV reduced HR variability (-56%, p=0.002) and ICABV variability (-64%, p=0.006) and increased ICABF variability (+140%, p=0.002) around RF. NIV+hypovolemia reduced variability in HR and ICABV by 70-80% (p=0.002) and doubled ICABF variability (p=0.03). MAP variability was unchanged in either condition. Respiration-induced HR and ICABV oscillations were in inverse phase and highly coherent (coherence >0.9) during baseline, but this coherence decreased during NIV, in normovolemia and hypovolemia (p=0.01). Controlling respiration in awake healthy humans reduced HR variability and increased CBF variability in hypovolemia and normovolemia. We suggest respiration-induced HR variability to be a mechanism in CBF regulation. Maintaining spontaneous respiration in patients receiving ventilatory support may be beneficial also for cerebral circulatory purposes.

Dynamic Cerebral Autoregulation During the Combination of Mild Hypercapnia and Cephalad Fluid Shift.

Mild hypercapnia combined with a cephalad fluid shift [e.g., that occurring during spaceflight or laparoscopic surgery with head-down tilt (HDT)] might affect cerebral autoregulation. However, no reports have described the effects of the combination on dynamic cerebral autoregulation. Therefore, we tested the hypothesis that the combination of mild hypercapnia and a cephalad fluid shift would attenuate dynamic cerebral autoregulation. There were 15 healthy male volunteers who were exposed to 4 10-min protocols in which they received air in the supine position (Placebo/Supine), 3% carbon dioxide (CO2) in the supine position (CO2/Supine), air with -10° HDT (Placebo/HDT) and 3% CO2 with -10° HDT (CO2/HDT). Dynamic cerebral autoregulation was evaluated using a transfer function analysis of the beat-to-beat variability in mean arterial blood pressure (ABP) and mean cerebral blood flow (CBF) velocity. The phase in the low-frequency range was significantly lower during CO2/HDT than all other protocols, where CO2/HDT was -25% lower than Placebo/Supine (CO2/HDT, 0.49 ± 0.21; Placebo/Supine, 0.65 ± 0.16 radians). The transfer function gain in the low-frequency range was significantly higher during CO2/HDT than all other protocols, where CO2/HDT was 26% higher than Placebo/Supine (CO2/HDT, 1.08 ± 0.34; Placebo/Supine, 0.86 ± 0.28 cm · s-1 · mmHg-1). However, neither the CO2/Supine nor Placebo/HDT showed significant differences compared with the Placebo/Supine. Even short-term exposure to 3% CO2 plus HDT increased synchrony and the magnitude of transmission between ABP and CBF in the low-frequency range. Thus, the combination of mild hypercapnia and a cephalad fluid shift attenuated dynamic cerebral autoregulation.Kurazumi T, Ogawa Y, Yanagida R, Morisaki H, Iwasaki K. Dynamic cerebral autoregulation during the combination of mild hypercapnia and cephalad fluid shift. Aerosp Med Hum Perform. 2017; 88(9):819-826.

The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.

Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. Case series, level IV.

Explore objective clinical variables for detecting delirium in ICU patients: a prospective case-control study

The aim of this case-control study is to explore clinical objective variables for diagnosing delirium of intensive care unit (ICU) patients. According to the method of prospective case-control study, critical adult postoperative patients who were transferred to ICU of Peking University People's Hospital from October 2015 to May 2016 and needed mechanical ventilation were included. After evaluating the Richmond agitation sedation scale score (RASS), the patients whose score were -2 or greater were sorted into two groups, delirium and non-delirium, according to the confusion assessment method for the ICU (CAM-ICU). Then these patients were observed by domestic multifunctional detector for electroencephalographic (EEG) variables such as brain lateralization, brain introvert, brain activity, brain energy consumption, focus inward, focus outward, cerebral inhibition, fatigue, sleep severity, sedation index, pain index, anxiety index, fidgety index, stress index and the cerebral blood flow (CBF) index which was named of perfusion index. Other variables including indexes of ICU blood gas analysis, which was consisted of variables of blood gas analysis, routine blood test and biochemistry, previous history and prognostic outcome was recorded. Binary logistic regression was used for multivariate analysis. Forty-three postoperative patients, who needed intensive care, were included. Eighteen were in delirium group and twenty-five in control group. Excluding the trauma, variables like gender, age, temperature, heart rate, respiratory rate, mean arterial pressure, acute physiology and chronic health evaluationII(APACHEII) score, organ failure, dementia and emergency surgery didn't show any statistical significance between two groups. The trauma in delirious patients increased obviously compared with the control group (33.3% vs. 4.0%, P = 0.031). Except for the brain activity [122.47 (88.62, 154.21) vs. 89.40 (86.27, 115.97), P = 0.034], there were no statistical differences in any other EEG and CBF variables. In ICU blood gas analysis, only pH value (7.43±0.42 vs. 7.47±0.31, P = 0.003), chloride concentration [Cl- (mmol/L): 114.66±4.32 vs. 111.90±3.08, P = 0.019], magnesium concentration [Mg2+ (mmol/L): 0.60±0.10 vs. 0.54±0.06, P = 0.035] and blood osmolality [mmol/L: 290.10 (284.15, 306.35) vs. 282.70 (280.20, 286.75), P = 0.014] were statistically significant. Compared with control group, the prognostic variables in delirium group such as duration of mechanical ventilation [days: 125.0 (49.0, 293.0) vs. 149.5 (32.0, 251.3)], length of stay in ICU [days: 216.5 (50.5, 360.8) vs. 190.0 (72.0, 330.5)] and mortality rate (22.2% vs. 24.0%) didn't appear to be statistically significant either (all P > 0.05). It was shown by multivariate logistic regression analysis that pH [odds ratio (OR) = 1.446, 95% confidence interval (95%CI) = 1.116-1.875, P = 0.005] and Cl- (OR = 0.708, 95%CI = 0.531-0.945, P = 0.019) were potential risk factors of delirium. The brain activity of HXD_I may contribute to the clinical diagnose of delirium, but it still remained to be proved further. The pH and Cl- are potential risk factors of delirium.

Neurovascular Complexity Index: A Potential Quantitative Measure for Assessment of Traumatic Brain Injury

Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case‐control study design, we evaluated a new proprietary algorithm of cerebral blood flow variability (CBFV) called the neurovascular complexity index (NCI). Baseline NCI data from 169 healthy control participants were compared to 51 TBI patients. Unadjusted and age‐sex adjusted logistic regression models were used to assess the association between NCI and TBI. TBI patients exhibited significantly greater variability in NCI scores than healthy controls (F=131.88; p&lt;0.0001). Compared to the continuous measure of NCI, the threshold of ± 1.96 standard deviations from the mean for the healthy control group measure (5.88&lt;NCI&gt;8.10) had superior ability to identify TBI patients based on the Receiver Operator Characteristic Area Under the Curve (0.84 vs. 0.61; p=0.0007), and greater sensitivity (74.5 vs. 51.0; p=0.0013). Individuals with NCI scores outside the 5.88–8.10 range had a 29‐fold increase in the odds of TBI in multivariate logistic regression models adjusted for age, sex and end tidal CO2 (OR=29.44; 95% CI 5.98–144.87; p&lt;0.0001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results for a new non‐invasive quantifiable assessment of TBI based on a measure of CBFV showing potential for continuous monitoring and early identification of brain‐injured patients to better inform individualized management.Support or Funding InformationUS Army MRMC Combat Casualty Care Research Program

Arterial Pressure, Heart Rate, and Cerebral Hemodynamics Across the Adult Life Span.

Age-related alterations in systemic and cerebral hemodynamics are not well understood. The purpose of this study is to characterize age-related alterations in beat-to-beat oscillations in arterial blood pressure (BP), heart rate (HR), cerebral blood flow (CBF), cardiac baroreflex sensitivity, and dynamic cerebral autoregulation across the adult life span. We studied 136 healthy adults aged 21 to 80 years (60% women). Beat-to-beat BP, HR, and CBF velocity were measured at rest and during sit-stand maneuvers to mimic effects of postural changes on BP and CBF. Transfer function analysis was used to assess baroreflex sensitivity and dynamic cerebral autoregulation. Carotid-femoral pulse wave velocity was measured to assess central arterial stiffness. Advanced aging was associated with elevated carotid-femoral pulse wave velocity, systolic and pulse BP, cerebrovascular resistance, and CBF pulsatility, but reduced mean CBF velocity. Compared with the young and middle-aged, older adults had lower beat-to-beat BP, HR, and CBF variability in the low-frequency ranges at rest, but higher BP and CBF variability during sit-stand maneuvers. Baroreflex sensitivity was reduced, whereas dynamic cerebral autoregulation gain was elevated at rest in older adults. Multiple linear regression analysis indicated that systolic BP variability is correlated positively with carotid-femoral pulse wave velocity independent of HR variability. In conclusion, advanced aging is associated with elevated pulsatility in BP and CBF; reduced beat-to-beat low-frequency oscillations in BP, HR, and CBF; and impaired baroreflex sensitivity and dynamic cerebral autoregulation at rest. The augmented BP and CBF variability in older adults during sit-stand maneuvers indicate diminished cardiovascular regulatory capability and increased hemodynamic stress on the cerebral circulation with aging.