Cerebral Hemodynamic Fluctuations Research Articles

Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3\xa0days after birth

A major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

Dynamic brain-body coupling of breath-by-breath O2-CO2 exchange ratio with resting state cerebral hemodynamic fluctuations.

BackgroundThe origin of low frequency cerebral hemodynamic fluctuations (CHF) in the resting state remains unknown. Breath-by breath O2-CO2 exchange ratio (bER) has been reported to correlate with the cerebrovascular response to brief breath hold challenge at the frequency range of 0.008–0.03Hz in healthy adults. bER is defined as the ratio of the change in the partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration. In this study, we aimed to investigate the contribution of respiratory gas exchange (RGE) metrics (bER, ΔPO2 and ΔPCO2) to low frequency CHF during spontaneous breathing.MethodsTwenty-two healthy adults were included. We used transcranial Doppler sonography to evaluate CHF by measuring the changes in cerebral blood flow velocity (ΔCBFv) in bilateral middle cerebral arteries. The regional CHF were mapped with blood oxygenation level dependent (ΔBOLD) signal changes using functional magnetic resonance imaging. Temporal features and frequency characteristics of RGE metrics during spontaneous breathing were examined, and the simultaneous measurements of RGE metrics and CHF (ΔCBFv and ΔBOLD) were studied for their correlation.ResultsWe found that the time courses of ΔPO2 and ΔPCO2 were interdependent but not redundant. The oscillations of RGE metrics were coherent with resting state CHF at the frequency range of 0.008–0.03Hz. Both bER and ΔPO2 were superior to ΔPCO2 in association with CHF while CHF could correlate more strongly with bER than with ΔPO2 in some brain regions. Brain regions with the strongest coupling between bER and ΔBOLD overlapped with many areas of default mode network including precuneus and posterior cingulate.ConclusionAlthough the physiological mechanisms underlying the strong correlation between bER and CHF are unclear, our findings suggest the contribution of bER to low frequency resting state CHF, providing a novel insight of brain-body interaction via CHF and oscillations of RGE metrics.

Impact of Healthy Aging on Multifractal Hemodynamic Fluctuations in the Human Prefrontal Cortex.

Fluctuations in resting-state cerebral hemodynamics show scale-free behavior over two distinct scaling ranges. Changes in such bimodal (multi) fractal pattern give insight to altered cerebrovascular or neural function. Our main goal was to assess the distribution of local scale-free properties characterizing cerebral hemodynamics and to disentangle the influence of aging on these multifractal parameters. To this end, we obtained extended resting-state records (N = 214) of oxyhemoglobin (HbO), deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration time series with continuous-wave near-infrared spectroscopy technology from the brain cortex. 52 healthy volunteers were enrolled in this study: 24 young (30.6 ± 8.2 years), and 28 elderly (60.5 ± 12.0 years) subjects. Using screening tests on power-law, multifractal noise, and shuffled data sets we evaluated the presence of true multifractal hemodynamics reflecting long-range correlation (LRC). Subsequently, scaling-range adaptive bimodal signal summation conversion (SSC) was performed based on standard deviation (σ) of signal windows across a range of temporal scales (s). Building on moments of different order (q) of the measure, σ(s), multifractal SSC yielded generalized Hurst exponent function, H(q), and singularity spectrum, D(h) separately for a fast and slow component (the latter dominating the highest temporal scales). Parameters were calculated reflecting the estimated measure at s = N (focus), degree of LRC [Hurst exponent, H(2) and maximal Hölder exponent, hmax] and measuring strength of multifractality [full-width-half-maximum of D(h) and ΔH15 = H(−15)−H(15)]. Correlation-based signal improvement (CBSI) enhanced our signal in terms of interpreting changes due to neural activity or local/systemic hemodynamic influences. We characterized the HbO-HbR relationship with the aid of fractal scale-wise correlation coefficient, rσ(s) and SSC-based multifractal covariance analysis. In the majority of subjects, cerebral hemodynamic fluctuations proved bimodal multifractal. In case of slow component of raw HbT, hmax, and Ĥ(2) were lower in the young group explained by a significantly increased rσ(s) among elderly at high temporal scales. Regarding the fast component of CBSI-pretreated HbT and that of HbO-HbR covariance, hmax, and focus were decreased in the elderly group. These observations suggest an attenuation of neurovascular coupling reflected by a decreased autocorrelation of the neuronal component concomitant with an accompanying increased autocorrelation of the non-neuronal component in the elderly group.

Cerebral Near-Infrared Spectroscopy: A Potential Approach for Thrombectomy Monitoring.

Regional brain oxygen saturation (rSO2) changes, assessed by cerebral near-infrared spectroscopy, are likely influenced by cerebral hemodynamic fluctuations induced by thrombectomy of acute proximal occlusion. We studied the correlations between rSO2 and baseline magnetic resonance imaging perfusion parameters and the relationship between rSO2 changes, recanalization, and clinical outcome. Seventeen acute ischemic stroke patients, treated with mechanical thrombectomy, were monitored using bilateral near-infrared spectroscopy before, during, and continuously for 24 hours after the procedure. All patients had baseline brain magnetic resonance imaging with perfusion weighted imaging. rSO2 was only correlated with baseline Tmax (ρ=-0.42; P<0.05) and mean transit time (ρ=-0.45; P<0.05) within forehead explored areas. Before thrombectomy, an interhemispheric rSO2 difference was noted, and this diminished over time when recanalization had occurred (median [interquartile range], -8 [-12 to -5] to 3 [-3 to 7]; P=0.01). rSO2 changes were not correlated with clinical outcome. rSO2 was merely correlated with baseline Tmax and mean transit time magnetic resonance imaging perfusion parameters. Multiple sites recording beyond frontal pole explored areas may provide more relevant correlation with hemodynamic parameters.

Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies.

The spontaneous cerebral hemodynamic fluctuations observed during the resting state have been frequently visualized using functional magnetic resonance imaging (rsfMRI). However, the neuronal populations and neuroelectric characteristics underlying the functional connectivity of cerebrohemodynamic activities are poorly understood. We investigated the characteristics of bi-hemispheric functional connectivity via electrophysiology and rsfMRI in the primary sensory cortex of rats anesthetized by α-chloralose. Unlike the evoked responses, the spontaneous electrophysiological activity was concentrated in the infragranular layers and could be classified into subtypes with distinctive current sources and sinks. Both neuroelectric and rsfMRI signals were interhemispherically correlated in a layer-specific manner, suggesting that there are independent neural inputs to infragranular and granular/supragranular layers. The majority of spontaneous electrophysiological activities were bilaterally paired with delays of up to ~50ms between each pair. The variable interhemispheric delay implies the involvement of indirect, multi-neural pathways. Our findings demonstrated the diverse activity patterns of layer-specific electrophysiological substrates and suggest the recruitment of multiple, non-specific brain regions in construction of interhemispheric functional connectivity.

Abstract 115: Snapshot MR-OEF for Simultaneous Imaging of Tissue Oxygenation and CVR in 90 Seconds

Introduction: Asymmetric hemispheric cerebral Oxygen Extraction Fraction (OEF) has been shown to be an independent predictor of stroke risk. Furthermore, the NIH/NINDS Progress Review Group has recently named tissue oxygenation imaging as a primary research goal in its August 2013 review. We have developed a novel method of imaging OEF with MRI. We present an analysis of MR-OEF images using breath-hold and cardiac-gating as inducers of physiologic stress. Methods: We acquire a 2D k-space volume using a novel rosette trajectory in 65 ms for simultaneous imaging of OEF and vascular reserve. Subjects were tested under 2 transient stress conditions: breath-hold and cardiac-gated. Breath-hold: 20 susceptibility weighted measurements were taken (Δt = 3 secs) with an induced 15 second breath-hold. Cardiac-gated: Because of the speed of PARSE (65 ms) we are able to see the transient hemodynamic fluctuations induced from the cardiac cycle. Images were acquired in 25 ms intervals from the R-wave trigger. Results: Measured mean OEF in normal brain parenchyma of 36.87 ± 6.6% and regions in symptomatic patients reaching 84.05 ± 4.54% correlate well with literature. OEF images taken during the first 125 ms of the cardiac cycle in a symptomatic patient with a right ICA stenosis are shown in Figure 1. Asymmetric hemispheric OEF (right hemispheric 13.06% elevation) is clearly visible. We also see a non-uniform flush in of de-oxygenated hemoglobin with a subsequent uneven outflow, unseen in healthy volunteers, suggesting regions of compromised cerebral vascular reserve. Discussion/Conclusion: Our novel acquisition allows us to simultaneously image single slice OEF and vascular reserve in 65 ms (with total scan time less than 90 seconds). Move over, because of its unprecedented speed, we for the first time, have the temporal resolution to examine the cerebral hemodynamic fluctuations caused by the pressure waveforms induced by the cardiac cycle.

Resting state functional connectivity of the whole head with near-infrared spectroscopy.

Resting state connectivity aims to identify spontaneous cerebral hemodynamic fluctuations that reflect neuronal activity at rest. In this study, we investigated the spatial-temporal correlation of hemoglobin concentration signals over the whole head during the resting state. By choosing a source-detector pair as a seed, we calculated the correlation value between its time course and the time course of all other source-detector combinations, and projected them onto a topographic map. In all subjects, we found robust spatial interactions in agreement with previous fMRI and NIRS findings. Strong correlations between the two opposite hemispheres were seen for both sensorimotor and visual cortices. Correlations in the prefrontal cortex were more heterogeneous and dependent on the hemodynamic contrast. HbT provided robust, well defined maps, suggesting that this contrast may be used to better localize functional connectivity. The effects of global systemic physiology were also investigated, particularly low frequency blood pressure oscillations which give rise to broad regions of high correlation and mislead interpretation of the results. These results confirm the feasibility of using functional connectivity with optical methods during the resting state, and validate its use to investigate cortical interactions across the whole head.

Periodic leg movements during sleep and cerebral hemodynamic changes detected by NIRS

Periodic leg movements during sleep (PLMS) have been shown to be associated with changes in autonomic and hemispheric activities. Near infrared spectroscopy (NIRS) assesses hemodynamic changes linked to hemispheric/cortical activity. We applied NIRS to test whether cerebral hemodynamic alterations accompany PLMS. Three PLMS patients underwent nocturnal polysomnography coupled with cerebral NIRS. EEG correlates of PLMS were scored and NIRS data were analysed for the identification of correspondent hemodynamic changes. PLMS were constantly associated with cerebral hemodynamic fluctuations that showed greater amplitude when associated to changes in EEG and were present also in absence of any visually detectable arousal or A phase in the EEG. This is the first study documenting cerebral hemodynamic changes linked to PLMS. The clinical relevance of these observations remains to be determined.

Effects of Rapid versus Slow Infusion of Sodium Bicarbonate on Cerebral Hemodynamics and Oxygenation in Preterm Infants

Background: Sodium bicarbonate (NaHCO₃) is often used for correction of metabolic acidosis in preterm infants. The effects of NaHCO₃ administration on cerebral hemodynamics and oxygenation are not well known. Furthermore, there is no consensus on infusion rate of NaHCO₃. Objectives: To evaluate the effects of rapid versus slow infusion of NaHCO₃on cerebral hemodynamics and oxygenation in preterm infants. Methods: Twenty-nine preterm infants with metabolic acidosis were randomized into two groups (values are mean ±SD): In group A (GA 30.5 ± 1.7 weeks, b.w. 1,254 ± 425 g) NaHCO₃ 4.2% was injected as a bolus. In group B (GA 30.3 ± 1.8 weeks, b.w. 1,179 ± 318 g) NaHCO₃ 4.2% was administered over a 30-min period. Concentration changes of oxyhemoglobin (cO₂Hb) and deoxyhemoglobin (cHHb) were assessed using near infrared spectrophotometry. Changes in HbD (= cO₂Hb – cHHb) represent changes in cerebral blood oxygenation and changes in ctHb (= cO₂Hb + cHHb) reflect changes in cerebral blood volume. Cerebral blood flow velocity was intermittently measured using Doppler ultrasound. Longitudinal data analysis was performed using linear mixed models (SAS procedure MIXED), to account for the fact that the repeated observations in each individual were correlated. Results: Administration of NaHCO₃ resulted in an increase of cerebral blood volume which was more evident if NaHCO₃was injected rapidly than when infused slowly. HbD and cerebral blood flow velocity did not show significant changes in either group. Conclusion: To minimize fluctuations in cerebral hemodynamics, slow infusion of sodium bicarbonate is preferable to rapid injection.

Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia.

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5(th)-95(th) centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral injury were 0.38 (0.23-0.53) on d 1, 0.31 (0.18-0.45) on d 2, and 0.28 (0.17-0.38) on d 3. Infants who developed cystic PVL had no significant change in cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1 to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral FOE values were seen in the two infants with HPI. The different patterns of change in cerebral FOE with HPI and cystic PVL provide additional evidence that the pathogenesis of these two conditions is different. Because high cerebral FOE is likely to be a consequence of low cerebral oxygen delivery, probably because of low cerebral blood flow, our results indicate that fluctuations in cerebral blood flow may occur when there is IVH or HPI.

HEMODYNAMIC CHANGES DURING BRIDGE OPENING IN VENO-ARTERIAL (VA) ECMO.316

Fluctuations in cerebral hemodynamics occurred during bridge opening in VA ECMO (Pediatr Res 1995,38:124-9). To investigate the cause of these effects the bridge was opened for 2.5 and 15 s at different flow rates (500 and 50 ml/min) in 8 lambs during VA ECMO. Changes (▵) in mean arterial blood pressure (MABP), central venous pressure (CVP), left common carotic artery blood flow (Qcar), cerebral total hemoglobin concentration (ctHb, measured with near infrared spectrophotometry), intracranial pressure (ICP), flow in the ECMO circuit on the venous side between lamb and bridge (VF), and on the arterial side between bridge and lamb (AF) were measured continuously during 60 s after opening of the bridge and were compared with the mean values in the 30 s preceding the opening. During opening of the bridge changes of flow direction occurred in VF and AF, resulting in a biphasic response of MABP and Qcar and an increase in CVP, ICP, and ctHb (representing cerebral bloodvolume). Values in the table are mean ± SD. These hemodynamic changes during opening of the bridge in VA ECMO, which were independent of ECMO flow rate and opening time duration, may carry a potential risk for intracranial pathology.

Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage.

We studied whether changes in cerebral blood-flow velocity occur during the respiratory-distress syndrome and whether, if present, they are related to the subsequent occurrence of intraventricular hemorrhage. Fifty infants weighing less than 1500 g at birth who required mechanical ventilation for the respiratory-distress syndrome were studied from the first hours of life. Blood-flow velocity in the anterior cerebral artery was measured at the anterior fontanel by means of the Doppler technique. At 12 hours of age, the infants had blood-flow velocity patterns that were either stable or fluctuating and that reflected the patterns of simultaneously recorded blood pressure. Intraventricular hemorrhage subsequently developed in 21 of 23 infants with the fluctuating pattern (in most of them, within the next 24 hours), but in only 7 of 27 infants with the stable pattern. Preliminary data suggest that the cerebral hemodynamic fluctuations are related to the respiratory disease and particularly to the mechanics of respiration. We conclude that the fluctuating pattern of cerebral blood-flow velocity in infants with the respiratory-distress syndrome indicates an extreme risk of the development of intraventricular hemorrhage and may represent a major and potentially preventable etiologic factor.