Cerebral blood flow and oxygenation at maximal exercise: the effect of clamping carbon dioxide

During exercise, as end-tidal carbon dioxide (P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$) drops after the respiratory compensation point (RCP), so does cerebral blood flow velocity (CBFv) and cerebral oxygenation. This low-flow, low-oxygenation state may limit work capacity. We hypothesized that by preventing the fall in P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ at peak work capacity (W_max) with a newly designed high-flow, low-resistance rebreathing circuit, we would improve CBFv, cerebral oxygenation, and W_max. Ten cyclists performed two incremental exercise tests, one as control and one with P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ constant (clamped) after the RCP. We analyzed , middle cerebral artery CBFv, cerebral oxygenation, and cardiopulmonary measures. At W_max, when we clamped P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ (39.7 ± 5.2 mmHg vs. 29.6 ± 4.7 mmHg, P < 0.001), CBFv increased (92.6 ± 15.9 cm/s vs. 73.6 ± 12.5 cm/s, P < 0.001). However, cerebral oxygenation was unchanged (ΔTSI −21.3 ± 13.1% vs. −24.3 ± 8.1%, P = 0.33), and W_max decreased (380.9 ± 20.4 W vs. 405.7 ± 26.8 W, P < 0.001). At W_max, clamping P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ increases CBFv, but this does not appear to improve W_max.     

Cerebral oxygenation and cerebral oxygen extraction in the preterm infant: the impact of respiratory distress syndrome

Haemodynamic factors play an important role in the etiology of cerebral lesions in preterm infants. Respiratory distress syndrome (RDS), a common problem in preterms, is strongly related with low and fluctuating arterial blood pressure. This study investigated the relation between mean arterial blood pressure (MABP), fractional cerebral oxygen saturation (ScO₂) and fractional (cerebral) tissue oxygen extraction (FTOE), a measure of oxygen utilisation of the brain, during the first 72 h of life. Thirty-eight infants (gestational age < 32 week) were included, 18 with and 20 without RDS. Arterial oxygen saturation (SaO₂), MABP and near infrared spectroscopy-determined ScO₂ were continuously measured. FTOE was calculated as a ratio: (SaO₂–ScO₂)/SaO₂. Gestational age and birth weight did not differ between groups, but assisted ventilation and use of inotropic drugs were more common in RDS infants (P<0.01). MABP was lower in RDS patients (P<0.05 from 12 up to 36 h after birth), but increased in both groups over time. ScO₂ and FTOE were not different between groups over time, but in RDS infants ScO₂ and FTOE had substantial larger variance (P<0.05 at all time points except at 36–48 h for ScO₂ and P<0.05 at 12–18, 18–24, 36–48 and 48–60 h for FTOE). During the first 72 h of life, RDS infants showed more periods of positive correlation between MABP and ScO₂ (P<0.05 at 18–24, 24–36 36–48 48–60 h) and negative correlation between MABP and FTOE (P<0.05 at 18–24, 36–48 h). Although we found that the patterns of cerebral oxygenation and extraction in RDS infants were not different as compared to infants without RDS, we suggest that the frequent periods with possible lack of cerebral autoregulation in RDS infants may make these infants more vulnerable to cerebral damage.     

癫癎患者脑血流速度改变与癫癎灶定侧的关系

目的 :探讨癫发作间期脑血流变化对癫灶定侧的价值。方法 :4 7例癫病人发作间期行经颅多普勒超声脑血流速度测定 ,并与临床、脑电图定位和MRI/CT病灶对比分析。结果 :根据临床症状确定病灶侧的 19例病人中 ,病灶侧脑血流速度改变 (升高和降低 )的比率显著高于双侧脑血流速度对称者 ;在脑电图确定病灶侧的 2 4例病人中 ,病灶侧脑血流速度升高比率显著高于脑血流速度降低和双侧脑血流速度对称者 ;在MRI确定病灶侧的 13例病人中 ,病灶侧脑血流速度增快 7例 ,减慢 2例 ,双侧血流速度对称 4例。结论 :癫病人一侧脑血流速度增高 ,高度提示癫病灶侧。     

Dynamics of regional cerebral blood flow for various visual stimuli

Summary Isotope tracer methods for measuring regional cerebral blood flow or metabolism do not provide data on the dynamics of the fast adjustment of local cerebral blood flow. Measuring intracranial flow patterns of the posterior cerebral artery by means or 2 MHz pulsed transcranial Doppler ultrasonography demonstrated that detailed dynamic effects of various visual patterns on local cerebral perfusion can be recorded, and that visual stimuli of different complexity as well as the strategy of stimulus perception cause distinct flow velocity changes in the occipital cortex involved in information processing. This type of on-line analysis may become a powerful tool for detecting fast autoregulatory mechanisms in relation to purely functional cerebral changes.Supported by the Deutsche Forschungsgemeinschaft (SFB 330 Organprotektion)     

Cerebral and peripheral hemodynamics and oxygenation during maximal dry breath-holds

The effects of maximal apneas on cerebral and brachial blood flow and oxygenation are unknown in humans. Middle cerebral artery blood velocity (MCAV), cerebral and muscle oxygenation (Sc(O2) and Sm(O2)) and brachial blood flow (BBF) were measured during apneas in breath-hold divers (BHD) and non-divers (ND). Brain oxyhemoglobin (O(2)Hb) was maintained in both groups until the end of apnea, whereas deoxyhemoglobin increased more in BHD. Therefore, Sc(O2) decreased more in BHD due to longer apnea duration and smaller initial MCAV increase. MCAV increased significantly more in BHD versus ND at the end of apnea. Cerebral desaturation for approximately 13% occurred at the end of apnea in BHD despite increased cerebral oxygen delivery for approximately 50%. Larger reduction in muscle O(2)Hb was found in BHD, with similar peripheral vasoconstriction. These data indicate that BHD have decreased Sc(O2) at the end of breath-hold despite large increases in MCAV. This is partly due delayed initial cerebral vasodilation. This study provides further evidence for the oxygen-conserving effect in elite divers.     

Effects of sensory modality on cerebral blood flow velocity during vigilance

Transcranial Doppler sonography was used to measure cerebral blood flow velocity (hemovelocity, CBFV) from the left and right middle cerebral arteries during the performance of 40-min auditory and visual vigilance tasks. Reductions in stimulus duration were the critical signals for detection in both tasks, which were equated for stimulus salience and discrimination difficulty. Signal detection responses (correct detections and false alarms) and CBFV declined significantly over time in a linear manner for both modalities. In addition, the overall level of CBFV and the temporal decline in this measure were greater in the right than the left cerebral hemisphere. The results are consistent with the view that a right hemispheric system is involved in the functional control of vigilance and that this system operates in a similar manner in the auditory and visual channels.     

Maintenance of cerebral blood flow and metabolism during pharmacological hypotension in aged hypertensive rats

Cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) were measured in aged (24 month) spontaneously hypertensive rats (SHR) during sodium nitroprusside (SNP) and nitroglycerin induced hypotension. Both CBF and CMRO2 were decreased in SHR during hypotension induced with SNP. Significant decrements in CMRO2 were observed in aged SHR during even moderate hypotension (80-90 torr). Cerebral autoregulatory responses during nitroglycerin infusion in aged SHR were similar to SNP treated WKY and CMRO2 was maintained at control levels under all hypotensive test conditions. These results indicate that aged SHR are susceptible to cerebral ischemia during SNP induced hypotension, probably due to the combined effects of aging and hypertension on the cerebral vasculature. NTG moderated the decreases in CBF and CMRO2 seen during hypotensive challenges and may decrease the risk of stroke during hypotensive anesthesia.     

Cognitive performance and cerebral blood flow in essential hypotension

In the present study cerebral blood flow was assessed in 40 subjects with chronically low blood pressure and 40 normotensive controls at resting conditions and during the execution of a cued reaction time task. Blood flow velocities were recorded by means of transcranial Doppler sonography in both middle cerebral arteries. In hypotensives flow velocity at rest was reduced bilaterally. During the anticipation of the stimuli, which the subjects had to respond to, a predominantly right hemispheric increase of flow velocity was observed in both groups. This increase was significantly less pronounced in the hypotensive group. Hypotensives showed longer reaction times, and there was a negative correlation between the extent of the flow velocity increase and the reaction times. This study is the first to demonstrate a reduced cerebral perfusion and maladaption of blood flow to cognitive demands due to essential hypotension.     

New prototype NIRS to investigate multi-regional cerebral blood and tissue oxygenation and haemodynamics

Near infra-red spectroscopy (NIRS) is a non-invasive optical technique used to assess blood and tissue oxygenation and haemodynamics in living tissue. It is presently used as a semi-continuous monitoring technique on a research basis. Multi-regional NIRS information could be beneficial for a better understanding of the development of cerebral injuries and the reduction of neurodevelopmental abnormalities in the human newborn. The paper presents the conversion of the continuous wave NIRS single-channel instrument (NIRDCU) into a prototype four-channel instrument which can be used to provide continuous multi-regional information regarding the cerebral blood oxygenation and haemodynamics in the frontal, left parietal, right parietal and occipital region of the neonatal brain. This has been achieved by attaching an optical multiplexing system to the NIRDCU to select different transmitting and receiving fibres, thus addressing different regions in the brain. Preliminary laboratory tests on a phantom and on the adult forearm are presented, illustrating the practicality of regional monitoring.     

Interactions between systemic hemodynamics and cerebral blood flow during attentional processing

The study explored interactions between systemic hemodynamics and cerebral blood flow during attentional processing. Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries (MCA) of both hemispheres were recorded while 50 subjects performed a cued reaction time task. Finger arterial pressure and heart rate were also continuously monitored. Doppler sonography revealed a right dominant blood flow response. The extent of the increase measured in second two of the interstimulus interval showed a clear positive association with reaction speed. Task‐related changes in blood pressure and heart rate proved predictive of changes in MCA flow velocities in limited time windows of the response. Besides an association between cerebral blood flow and attentional performance, the results suggest a marked impact of systemic hemodynamics on the blood flow response. All observed interactions are highly dynamic in time.     

Differential cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations

The potential differences in cerebrovascular responses between the anterior and posterior circulations to changes in CO₂ are unclear in humans. Using transcranial Doppler ultrasound, we compared the CO₂ reactivity of the (1) BA and PCA and (2) MCA and PCA during hyperoxic rebreathing in supine position. The reactivity in the BA and PCA was similar in both absolute (1.27 ± 0.5 and 1.27 ± 0.6 cm/s/Torr; P = 0.992) and relative (3.98 ± 1.3 and 3.66 ± 1.5%/Torr CO₂; P = 0.581) measures, suggesting that the PCA is an adequate surrogate measure of reactivity for the BA. The MCA reactivity was greater than the PCA in absolute (2.09 ± 0.7 and 1.22 ± 0.5 cm/s/Torr CO₂; P < 0.001), but not relative measures (3.25 ± 1.0 and 3.56 ± 1.6%/Torr CO₂; P = 0.629). Our findings (a) confirm regional differences in the absolute reactivity in the human brain and (b) suggest that in cerebrovascular studies investigating functions mediated by posterior brain structures (e.g., control of breathing), the posterior vasculature should also be insonated.     

Brain volume and white matter hyperintensities as determinants of cerebral blood flow in Alzheimer's disease

To better understand whether decreased cerebral blood flow (CBF) in patients with Alzheimer's disease (AD) reflects neurodegeneration or cerebral small vessel disease, we investigated the associations of normalized brain volume (NBV) and white matter hyperintensity (WMH) volume with CBF. We included 129 patients with AD (66 ± 7 years, 53% female) and 61 age-matched controls (64 ± 5 years, 43% female). CBF was measured with pseudocontinuous arterial spin labeling at 3T in the whole brain and in partial volume corrected cortical maps. When NBV and WMH were simultaneously entered in age and sex adjusted models, smaller NBV was associated with lower whole brain (Stβ: 0.29; p < 0.01) and cortical CBF (Stβ: 0.28; p < 0.01) in patients with AD. Larger WMH volume was also associated with lower whole brain (Stβ: −0.22; p < 0.05) and cortical CBF (Stβ: −0.24; p < 0.05) in AD. Additional adjustments did not change these results. In controls, neither NBV nor WMH was associated with CBF. Our results indicate that in AD, lower CBF as measured using pseudocontinuous arterial spin labeling, reflects the combined disease burden of both neurodegeneration and small vessel disease.     

Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease

Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimer's disease (AD). However, alterations in vascular function under in vivo conditions are poorly understood. In this study, we assessed cerebrovascular-reactivity (CVR) in AD patients and age-matched controls using CO₂-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared with controls, AD patients had widespread reduction in CVR in the rostral brain including prefrontal, anterior cingulate, and insular cortex (p < 0.01). The deficits could not be explained by cardiovascular risk factors. The spatial distribution of the CVR deficits differed drastically from the regions of cerebral blood flow (CBF) deficits, which were found in temporal and parietal cortices. Individuals with greater CVR deficit tended to have a greater volume of leukoaraiosis as seen on FLAIR MRI (p = 0.004). Our data suggest that early AD subjects have evidence of significant forebrain vascular contractility deficits. The localization, while differing from CBF findings, appears to be spatially similar to PIB amyloid imaging findings.     

Enhancement of cerebral blood flow and cognitive performance following pharmacological blood pressure elevation in chronic hypotension

Previous research has demonstrated reduced cognitive performance and diminished cerebral blood flow in the case of chronic hypotension. We investigated whether these deficits can be reduced by pharmacological blood pressure elevation. Effects of the sympathomimetic midodrine were examined in 50 hypotensive individuals based on a randomized, placebo-controlled double-blind design. A paper-pencil test assessing performance in selective attention was presented. By means of transcranial Doppler sonography, blood flow velocities were recorded in both middle cerebral arteries at rest and during the execution of a cued reaction time task. The administration of midodrine led to an increase in blood flow velocities at rest as well as enhanced attentional performance. The degree of rise in flow velocities was positively correlated with performance enhancement. The increase in flow velocities observed during the execution of the reaction time task was stronger following drug administration.     

Deficient adjustment of cerebral blood flow to cognitive activity due to chronically low blood pressure

The present study aimed to investigate aberrances in the adjustment of cerebral blood flow to cognitive activity due to chronically low blood pressure. By means of transcranial Doppler sonography blood flow velocities in both middle cerebral arteries (MCA) were recorded during the execution of a serial subtraction task in 40 subjects with constitutional hypotension and 40 normotensive control persons. Additionally, blood pressure was continuously monitored. As a main result significant correlations between the task-induced changes in blood pressure and those in MCA blood flow velocities were found in hypotensives, but not in control subjects. The dependence of the regulation of cerebral blood flow on blood pressure points towards deficits in cerebral autoregulation in hypotension. Over the total sample the extent of the task-induced MCA flow velocity increase was positively related to cognitive performance. This underlines the importance of the adjustment of cerebral blood flow to current demands for optimal cognitive functioning.     

Acceleration of cortical thinning in familial Alzheimer's disease

Background

MRI in presymptomatic autosomal dominant Alzheimer's disease mutation carriers (MC) provides an opportunity to detect changes that pre-date symptoms or clinical diagnosis. We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls.

Methods

9 presymptomatic mutation carriers (4 PSEN1, 5 APP) and 25 healthy, age and sex-matched controls underwent longitudinal volumetric MRI brain imaging. CTh measurement was performed across the whole brain using a validated, automated technique. Four regions of interest (ROI) (entorhinal cortex (ERC), parahippocampal gyrus (PHG), posterior cingulate cortex and precuneus) and two control regions (paracentral and pericalcarine) were selected on the basis of imaging data in existing Alzheimer's disease (AD) literature. Linear mixed models were used to describe normal ageing in controls and the extent to which mean CTh in cases differed from controls according to time since clinical diagnosis, adjusting for normal ageing.

Results

An accelerating decline in CTh was observed across all ROI in the MC group. No such decline was demonstrated in the control regions for the MC group. Relative to controls, and adjusting for normal ageing, there was evidence (p = 0.05, one-sided test) of lower CTh in the posterior cingulate up to 1.8 years prior to diagnosis and in the precuneus up to 4.1 years prior to diagnosis in the MC group.

Discussion

Automated CTh analysis is a relatively practical, rapid and effective technique for assessing subtle structural change in AD. There is evidence that cortical thickness is reduced in mutation carriers a number of years prior to clinical diagnosis.     

Estimating normal and pathological dynamic responses in cerebral blood flow velocity to step changes in end-tidal pCO2

The regulation of cerebral blood flow (CBF) following changes in arterial blood pressure (ABP) and end-tidal pCO₂ (EtCO₂) are of clinical interest in assessing cerebrovascular reserve capacity. Linear finite-impulse-response modelling is applied to ABP, EtCO₂ and CBF velocity (CBFV, from transcranial Doppler measurements), which allows the CBFV response to ideal step changes in EtCO₂ to be estimated from clinical data showing more sluggish, and additional random variations. The confounding effects of ABP changes provoked by hypercapnia on the CBFV are also corrected for. Data from 56 patients suffering from stenosis of the carotid arteries (with normal or diminished cerebrovascular reactivity to EtCO₂ changes—CVR_{CO 2} were analysed. The results show the expected significant differences (p<0.05) between EtCO₂ steps up and down, the significant contribution from ABP variation, and also differences in the dynamic responses of patients with reduced CVR_{CO 2} (p<0.01 after 10 s). For the latter the CBFV response appears exhausted after about 15s, whereas for normals CBFV continues to increase. While dispersion of individual step responses remains large, the method gives encouraging results for the non-invasive study of compromised haemodynamics in different patient groups.     

Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances

The role of cerebral amyloid angiopathy (CAA) in the pathogenesis of Alzheimer's disease (AD) is not fully understood. Here, we studied whether CAA is associated with alterations in microvascularisation in transgenic mouse models and in the human brain. APP23 mice at 25–26 months of age exhibited severe CAA in thalamic vessels whereas APP51/16 mice did not. Wild-type littermates were free of CAA. We found CAA-related capillary occlusion within the thalamus of APP23 mice but not in APP51/16 and wild-type mice. Magnetic resonance angiography (MRA) showed blood flow alterations in the thalamic vessels of APP23 mice. CAA-related capillary occlusion in the branches of the thalamoperforating arteries of APP23 mice, thereby, corresponded to the occurrence of blood flow disturbances. Similarly, CAA-related capillary occlusion was observed in the human occipital cortex of AD cases but less frequently in controls. These results indicate that capillary CAA can result in capillary occlusion and is associated with cerebral blood flow disturbances providing an additional mechanism for toxic effects of the amyloid β-protein in AD.     

Optimising the methodology of calculating the cerebral blood flow of newborn infants from near infra-red spectrophotometry data

Cerebral blood flow can be measured in neonates by near infra-red spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to compare the test-retest variability of two previously proposed methods (UCH and COP) of analysis, and to investigate the influence of sampling rates, smoothing and integration periods. Under clinical conditions good measurements are often difficult to obtain. Therefore, a second goal is to find ways of determining the quality of individual measurements. 380 cerebral blood flow measurements from 69 infants are analysed. The data set is optimised statistically for the lowest test-retest variability and the following results are obtained. The test-retest variability of measurements at 2 s sampling time data is considerably worse than at 0·5 s sampling time. Smoothing does not change the test retest variability. A 6 s integration period gives higher values and higher test-retest variability than an 8 s integration period. By applying the suggested criteria, a test-retest variability of 17% is achieved, if 50% of the measurements are rejected. The mean cerebral blood flow is 12·2 ml(100 g)⁻¹ min⁻¹ for the UCH method and 97·7 ml(100 g)⁻¹ min⁻¹ for the COP method. The test-retest variability of both methods is comparable for 0·5 s sampling time. For 2 s sampling time the method proposed by Skov et al. is significantly better. These test retest variabilities represent maximum values, part of the observed variability may be due to physiological changes of unknown magnitude.