Middle Cerebral Blood Velocity Research Articles

Dynamics of Critical Closing Pressure Explain Cerebral Autoregulation Impairment in Acute Cerebrovascular Disease.

Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients. Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 s) peak in CrCP dynamic response that was not influenced by age. These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature.

CO2 supplementation dissociates cerebral oxygenation and middle cerebral artery blood velocity during maximal cycling.

This study evaluated whether the reduction of prefrontal cortex oxygenation (ScO2 ) during maximal exercise depends on the hyperventilation-induced hypocapnic attenuation of middle cerebral artery blood velocity (MCA Vmean ). Twelve endurance-trained males (age: 25±3years, height: 183±8cm, weight: 75±9kg; mean±SD) performed in three separate laboratory visits, a maximal oxygen uptake (VO2 max) test, an isocapnic (end-tidal CO2 tension (PetCO2 ) clamped at 40±1mmHg), and an ambient air controlled-pace constant load high-intensity ergometer cycling to exhaustion, while MCA Vmean (transcranial Doppler ultrasound) and ScO2 (near-infrared spectroscopy) were determined. Duration of exercise (12min 25s±1min 18s) was matched by performing the isocapnic trial first. Pulmonary VO2 was 90±6% versus 93±5% of the maximal value (P=.012) and PetCO2 40±1 versus 34±4mmHg (P<.05) during the isocapnic and control trials, respectively. During the isocapnic trial MCA Vmean increased by 16±13% until clamping was applied and continued to increase (by 14±28%; P=.017) until the end of exercise, while there was no significant change during the control trial (P=.071). In contrast, ScO2 decreased similarly in both trials (-3.2±5.1% and -4.1±9.6%; P<.001, isocapnic and control, respectively) at exhaustion. The reduction in prefrontal cortex oxygenation during maximal exercise does not depend solely on lowered cerebral blood flow as indicated by middle cerebral blood velocity.

Severity-dependent influence of isocapnic hypoxia on reaction time is independent of neurovascular coupling

With exposure to acute normobaric hypoxia, global cerebral oxygen delivery is maintained via increases in cerebral blood flow (CBF); therefore, regional and localized changes in oxygen tension may explain neurocognitive impairment. Neurovascular coupling (NVC) is the close temporal and regional relationship of CBF to changes in neural activity and may aid in explaining the localized CBF response with cognitive activation. High-altitude related cognitive impairment is likely affected by hypocapnic cerebral vasoconstriction that may influence regional CBF regulation independent of hypoxia. We assessed neurocognition and NVC following 30 min of acute exposure to isocapnic hypoxia (decreased partial pressure of end-tidal oxygen; PETO2) during moderate hypoxia (MOD HX; 55 mm Hg PETO2), and severe hypoxia (SEV HX; 45 mm Hg PETO2) in 10 healthy individuals (25.5 ± 3.3 yrs). Transcranial Doppler ultrasound was used to assess mean posterior and middle cerebral blood velocity (PCAv and MCAv, respectively) and neurocognitive performance was assessed via validated computerized tests. The main finding was that reaction time (i.e., kinesthetic and visual-motor ability via Stroop test) was selectively impaired in SEV HX (−4.6 ± 5.2%, P = 0.04), but not MOD HX, while complex cognitive performance (e.g., psychomotor speed, cognitive flexibility, processing speed, executive function, and motor speed) was unaffected with hypoxia (P > 0.05). Additionally, severity of hypoxia had no effect on NVC (PCAv CON vs. SEV HX relative peak response 13.7 ± 6.4% vs. 16.2 ± 11.5%, P = 0.71, respectively). In summary, severe isocapnic hypoxia impaired reaction time, but not complex cognitive performance or NVC. These findings have implications for recreational and military personnel who may experience acute hypoxia.

Detection of Impaired Sympathetic Cerebrovascular Control Using Functional Biomarkers Based on Principal Dynamic Mode Analysis.

This study sought to determine whether models of cerebrovascular function based on Laguerre-Volterra kernels that account for nonlinear cerebral blood flow (CBF) dynamics can detect the effects of functional cerebral sympathetic blockade. We retrospectively analyzed continuous beat-to-beat blood pressure, middle cerebral blood velocity, and partial-pressure of end-tidal CO2 (PETCO2) recordings from eighteen healthy individuals who were treated with either an oral dose of the α1-adrenergic receptor blocker Prazosin or a placebo treatment. The global principal dynamic modes (PDMs) were analyzed using Laguerre-Volterra kernels to examine the nonlinear system dynamics. Our principal findings were: (1) very low frequency (<0.03 Hz) linear components of first-order kernels for BP and PETCO2 are mutually coupled to CBF dynamics with the ability to separate individuals between control and blockade conditions, and (2) the gains of the nonlinear functions associated with low-pass and ≈0.03 Hz global PDMs for the BP are sensitive to sympathetic blockade. Collectively these results suggest that very low frequency global PDMs for BP may have potential utility as functional biomarkers of sympathetic neurovascular dysfunction which can occur in conditions like autonomic failure, stroke and traumatic brain injury.

Non‐linear Relationships between Blood Pressure and Cerebral Blood Flow

High metabolic demands make cerebrovascular tissue vulnerable to ischaemic brain injury. To protect from these morbid conditions the brain needs stringent control of cerebral perfusion. The foremost physiological mechanism augmenting the active dilation/constriction of blood arterioles while ensuring relatively constant cerebral blood flow in response to perfusion pressure instabilities (within 60-150 mmHg) is attributed to dynamic cerebral autoregulation (CA). In this study we sought to determine the consistency of dynamic CA by characterising the pressure-flow relationships. We recorded blood pressure (BP) and middle cerebral blood velocity (MCAv) in 18 healthy, normotensive and non-smoking volunteers (9 females, 23±3 years) under spontaneous baseline conditions and during application of oscillatory lower body negative pressure. In this study we pursued non-linear regression approaches, viz locally weighted scatter plot smoothing and conditional kernel density estimation, to characterise the human cerebral BP-MCAv dynamics and compared these to previously adopted linear and non-linear approaches used for CA quantification. Additionally, we also proposed piecewise linear regression for independent BP-MCAv data values to statistically evaluate the hypothesis that a dynamic CA plateau is consistently observed across individuals. We observed diverse BP-MCAv patterns with few individuals demonstrating clear evidence of a CA plateau. The findings of the current study suggest that: 1) dynamic CA is a physiologically diverse phenomenon; 2) BP alone is a poor surrogate indicator of brain perfusion and 3) multivariate quantification models that take into account other processes e.g., CO2 reactivity and neurovascular coupling, should be adopted.

The Effects of Preterm Birth on Cerebral Pressure‐Flow Dynamics

Altered cortical and neurodevelopmental outcomes have been described following very preterm birth and imparied blood pressure (BP) and cerebral blood flow regulation have been implicated as possible mechanisms. However, whether haemodynamic impairment persists into early childhood following preterm birth remains unclear. To test the hypothesis that cerebrovascular dysfunction persists in early childood (age 6.6 yrs ±0.8) following preterm brith, we recorded BP and middle cerebral blood velocity (MCAv) in 10 preterm children (5 males, mean gestastion age at birth =32.2 weeks ±2.7) and 10 children born at term (5 males, mean gestation age at birth =39.7 weeks ±1.0) under spontaneous baseline conditions. Cerebral BP-MCAv dynamics were assessed using linear transfer function analysis. Additionally, we applied Granger's causlity test to determine the direction and strength of BP-MCAv interactions using Vector Autoregressive Moving Average Models. Results showed that compared to term children, BP-MCAv coherence was higher in preterm females (0.35±0.079 vs. 0.58±0.086, p=0.08) but similar in males (0.41±0.072 vs. 0.049±0.10, p=0.53). The average directionality index was similar between term and preterm children but the standard deviation was greater in preterm children (-7.2±13.33 vs -7.8±32.25). Further, the directionality index was positively correlated to the transfer function coherence (r=48, p<0.05). These results indicate that preterm females may have impaired cerebrovacular regulation and that, as a group, preterm children are more likley to exhibit pressure-flow dynamics that are dominated by either BP or cerebral blood flow.

Fundamental relationships between blood pressure and cerebral blood flow in humans.

Cerebral blood flow responses to transient blood pressure challenges are frequently attributed to cerebral autoregulation (CA), yet accumulating evidence indicates vascular properties like compliance are also influential. We hypothesized that middle cerebral blood velocity (MCAv) dynamics during or following a transient blood pressure perturbation can be accurately explained by the windkessel mechanism. Eighteen volunteers underwent blood pressure manipulations, including bilateral thigh-cuff deflation and sit-to-stand maneuvers under normocapnic and hypercapnic (5% CO2) conditions. Pressure-flow recordings were analyzed using a windkessel analysis approach that partitions the frequency-dependent resistance and compliance contributions to MCAv dynamics. The windkessel was typically able to explain more than 50% of the MCAv variance, as indicated by R(2) values for both the flow recovery and postrecovery phase. The most consistent predictors of MCAv dynamics under the control condition were the windkessel capacitive gain and high-frequency resistive gain. However, there were significant interindividual variations in the composition of windkessel predictors. Hypercapnia consistently reduced the capacitive gain and enhanced the low-frequency (0.04-0.20 Hz) resistive gain for both thigh-cuff deflation and sit-to-stand trials. These findings indicate that 1) MCAv dynamics during acute transient hypotension challenges are dominated by cerebrovascular windkessel properties independent of CA; 2) there is significant heterogeneity in windkessel properties between individuals; and 3) hemodynamic effects of hypercapnia during transient blood pressure challenges primarily reflect changes in windkessel properties rather than pure CA impairment.

The influence of combined lower body negative pressure and mental stress on cerebral blood flow in men and women

Lower body negative pressure (LBNP) decreases mean middle cerebral blood velocity (MCAv) and mental stress (MS) typically increases MCAv, but the MCAv response to these combined autonomic stressors is unknown. We hypothesized that performing MS during LBNP would result in an additive MCAv interaction. Eighteen participants (9 men, 9 women) completed three randomized trials: 1) 3 min LBNP (−40 mmHg), 2) 3 min MS (serial subtraction), and 3) combined LBNP and MS. Mean arterial pressure (MAP), heart rate (HR) and MCAv were continuously measured. Baseline MAP (81±2 vs. 80±1 vs. 80±1 mmHg) and HR (65±2 vs. 64±2 vs. 65±2 beats/min) were similar preceding each trial. LBNP significantly (p&lt;0.05) decreased MCAv (Δ−3±1 cm/s), but did not alter MAP or HR. MS significantly (p&lt;0.05) increased MAP (Δ10±1 mmHg), HR (Δ17±2 beats/min) and MCAv (Δ3±1 cm/s; p=0.05). Combined LBNP and MS significantly (P&lt;0.05) increased MAP (Δ7±3 mmHg) and HR (Δ18±4 beats/min) and significantly decreased MCAv (Δ−5±2 cm/s). Increases in MAP and HR were similar during the combination trial when compared to the calculated sum of the individual trials. However, the MCAv (Δ−5±2 vs. Δ0±2 cm/s) response was blunted during the combination trial vs. the sum of individual trials. In conclusion, our findings are contrary to our hypothesis and suggest there is not an additive MCAv interaction during combined cognitive and orthostatic stress.Supported by NASA.

Influence of sympathoexcitation at high altitude on cerebrovascular function and ventilatory control in humans

We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3-10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco(2) and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated (P < 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02-0.07 Hz) increased, and phase lead was reduced (all P < 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (-40 ± 23%; P < 0.01). In contrast, blockade at HA reduced low-frequency coherence (-26 ± 20%; P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238%; P < 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA (P < 0.01), blockade increased it comparably at SL and HA (∼43-68%; P < 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced (P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.

Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements

To establish reference ranges suitable for serial assessments of the fetal middle cerebral (MCA) and umbilical (UA) artery blood flow velocities, pulsatility index (PI) and cerebroplacental pulsatility ratio and to provide terms for calculating conditional reference intervals suitable for individual serial measurements. This was a longitudinal study of 161 singleton pregnancies. Using Doppler ultrasound, MCA and UA blood velocities and PI were determined three to five times at 3-5-week intervals over a gestational age range of 19-41 weeks. Polynomial regression lines for the 95th, 50th and 5th percentiles were calculated for the peak systolic velocity (PSV), time-averaged maximum velocity (TAMXV), PI and cerebroplacental ratio. Terms for calculating conditional reference intervals were established. Based on 566 observations our new longitudinal reference ranges for fetal middle cerebral PSV, TAMXV and PI provided terms for calculating conditional reference intervals (i.e. predicting expected 95% confidence limits based on a previous measurement), and correspondingly for the cerebroplacental ratio (n = 550). The reference ranges were at some variance with those of previous cross-sectional studies. The narrow 95% confidence limits for the 5(th) and 95(th) percentiles ensured reliable ranges. We have established longitudinal reference ranges appropriate for the serial assessment of MCA blood velocities and PI and cerebroplacental ratio. Particularly the terms for calculating conditional ranges based on a previous observation make this system more appropriate for longitudinal monitoring than are cross-sectional data.

Monitoring middle cerebral artery blood velocity during carotid endarterectomy: Padayachee T, Gossling S, Biship RG, et al. Br J Surg 1986;73:98–100

The authors report that intraoperative monitoring of middle cerebral blood velocity during carotid endarterectomy has been achieved by means of a transcranial pulsed Doppler ultrasound. The spectral analysis of the blood flow of the middle cerebral artery was correlated with the various stages of the operation. In 19 patients, the authors demonstrate that there is a decrease in the middle cerebral artery blood velocity during carotid clamping. Blood velocity returns to normal or increases with placement of a carotid shunt. In several patients, during back-bleeding of the internal carotid artery, there was a reversal of flow in the middle cerebral artery, suggesting a shunt phenomenon. This is the first report of a study of intraoperative middle cerebral artery blood flow in the literature and it is remarkable for observing intracerebral blood flow changes during the maneuvers of carotid surgery. The authors do not know whether there is any particular significance regarding the changes of blood velocity of the middle cerebral artery. Specifically, it is too early to know whether this technique will be able to select which patients will have cerebral ischemia with carotid clamping since there were no concomitant measurements of cerebral ischemia in this study. Further studies will be needed to determine whether this technique will provide a means of monitoring patients during carotid surgery.

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: Velocity as an index of flow

Blood velocities have been measured transcranially, at small Doppler angles, in the middle cerebral artery of normal volunteers. Cerebral blood flow was changed by varying carbon dioxide tension. In four volunteers, the relationships between arterial pCO2 and percentage change in intensity weighted mean, median, and maximum Doppler-shifted frequencies in the internal carotid and middle cerebral arteries were linear with slopes of 2.5 and 2.8% per mm Hg change in pCO2. In 38 volunteers, the relationship between end-expiratory pCO2 and time-averaged maximum Doppler frequency was linear over the range of pCO2 20-60 mm Hg with slopes of 2.5 and 2.9 percentage change per mm Hg, for internal carotid and middle cerebral, respectively. These results are very similar to those reported using direct methods of measuring cerebral blood flow. As the transcranial Doppler method is reproducible, this indicates that changes in middle cerebral blood velocity may be used to monitor changes in flow.