Product Of Cerebral Blood Flow Research Articles

The Role of Brain Tissue Oxygenation Monitoring in the Management of Subarachnoid Hemorrhage: A Scoping Review.

Monitoring of brain tissue oxygenation (PbtO2) is an important component of multimodal monitoring in traumatic brain injury. Over recent years, use of PbtO2 monitoring has also increased in patients with poor-grade subarachnoid hemorrhage (SAH), particularly in those with delayed cerebral ischemia. The aim of this scoping review was to summarize the current state of the art regarding the use of this invasive neuromonitoring tool in patients with SAH. Our results showed that PbtO2 monitoring is a safe and reliable method to assess regional cerebral tissue oxygenation and that PbtO2 represents the oxygen available in the brain interstitial space for aerobic energy production (i.e., the product of cerebral blood flow and the arterio-venous oxygen tension difference). The PbtO2 probe should be placed in the area at risk of ischemia (i.e., in the vascular territory in which cerebral vasospasm is expected to occur). The most widely used PbtO2 threshold to define brain tissue hypoxia and initiate specific treatment is between 15 and 20mm Hg. PbtO2 values can help identify the need for or the effects of various therapies, such as hyperventilation, hyperoxia, induced hypothermia, induced hypertension, red blood cell transfusion, osmotic therapy, and decompressive craniectomy. Finally, a low PbtO2 value is associated with a worse prognosis, and an increase of the PbtO2 value in response to treatment is a marker of good outcome.

Initial Experience of Challenge-Free MRI-Based Oxygen Extraction Fraction Mapping of Ischemic Stroke at Various Stages: Comparison With Perfusion and Diffusion Mapping.

MRI-based oxygen extraction fraction imaging has a great potential benefit in the selection of clinical strategies for ischemic stroke patients. This study aimed to evaluate the performance of a challenge-free oxygen extraction fraction (OEF) mapping in a cohort of acute and subacute ischemic stroke patients. Consecutive ischemic stroke patients (a total of 30 with 5 in the acute stage, 19 in the early subacute stage, and 6 in the late subacute stage) were recruited. All subjects underwent MRI including multi-echo gradient echo (mGRE), diffusion weighted imaging (DWI), and 3D-arterial spin labeling (ASL). OEF maps were generated from mGRE phase + magnitude data, which were processed using quantitative susceptibility mapping (QSM) + quantitative blood oxygen level-dependent (qBOLD) imaging with cluster analysis of time evolution. Cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were reconstructed from 3D-ASL and DWI, respectively. Further, cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of CBF and OEF. OEF, CMRO2, CBF, and ADC values in the ischemic cores (absolute values) and their contrasts to the contralateral regions (relative values) were evaluated. One-way analysis of variance (ANOVA) was used to compare OEF, CMRO2, CBF, and ADC values and their relative values among different stroke stages. The OEF value of infarct core showed a trend of decrease from acute, to early subacute, and to late subacute stages of ischemic stroke. Significant differences among the three stroke stages were only observed in the absolute OEF (F = 6.046, p = 0.005) and relative OEF (F = 5.699, p = 0.009) values of the ischemic core, but not in other measurements (absolute and relative CMRO2, CBF, ADC values, all values of p > 0.05). In conclusion, the challenge-free QSM + qBOLD-generated OEF mapping can be performed on stroke patients. It can provide more information on tissue viability that was not available with CBF and ADC and, thus, may help to better manage ischemic stroke patients.

Cerebral metabolism, oxidation and inflammation in severe passive hyperthermia with and without respiratory alkalosis.

It was unknown whether respiratory alkalosis impacts the global cerebral metabolic response as well as the cerebral pro-oxidation and inflammatory response in passive hyperthermia. This study demonstrated that the cerebral metabolic rate was increased by ∼20% with passive hyperthermia of up to +2°C oesophageal temperature, and this response was unaffected by respiratory alkalosis. Additionally, the increase in cerebral metabolism did not significantly impact the net cerebral release of oxidative and inflammatory markers. These data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, but it does markedly increase the cerebral metabolic rate, independently of . There is limited information concerning the impact of arterial /pH on heat-induced alteration in cerebral metabolism, as well as on the cerebral oxidative/inflammatory burden of hyperthermia. Accordingly, we sought to address two hypotheses: (1) passive hyperthermia will increase the cerebral metabolic rate of oxygen (CMRO2 ) consistent with a combined influence of Q10 and respiratory alkalosis; and (2) the net cerebral release of pro-oxidative and pro-inflammatory markers will be elevated in hyperthermia, particularly in poikilocapnic hyperthermia. Healthy young men (n=6) underwent passive heating until an oesophageal temperature of 2°C above resting was reached. At 0.5°C increments in core temperature, CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Net cerebral glucose/lactate exchange, and biomarkers of oxidative and inflammatory stress were also measured. At +2.0°C oesophageal temperature, arterial was restored to normothermic values using end-tidal forcing. The primary findings were: (1) while CMRO2 was increased (P<0.05) by ∼20% with hyperthermia of +1.5-2.0°C, this was not influenced by respiratory alkalosis, and (2) although biomarkers of pro-oxidation and pro-inflammation were systemically elevated in hyperthermia (P<0.05), there were no differences in the trans-cerebral exchange kinetics. These novel data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, despite it markedly increasing CMRO2 , irrespective of arterial pH.

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Advances in Understanding Ischemic Stroke Physiology and the Impact of Vasculopathy in Children With Sickle Cell Disease.

Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide, with over 300,000 children born with SCD each year.1 Neurologic consequences of SCD include ischemic and hemorrhagic strokes2 and cognitive deficits.3 SCD accounts for almost ¼ of all stroke-related hospitalizations in African-American children.4 Historically, ischemic stroke in SCD has been separated by symptomatology, including “overt stroke,” referring to radiographic ischemia with associated neurologic deficits detectable on a bedside examination, and “silent stroke” referring to radiographic ischemia without focal neurologic deficits, but associated with cognitive deficits. However this dichotomy is likely false, as the two can be radiographically indistinguishable.5 Strokes may have lifelong devastating consequences, including limited educational attainment and decreased quality of life in children.6, 7 Sickle cell anemia refers to the most severe SCD phenotypes, SS and Sβ0 thalassemia, which have the highest stroke incidence. However, other SCD genotypes are also at risk for cerebral ischemia, with up to 13% of HbSC children having silent ischemia on screening MRI.2, 8 Transcranial Doppler (TCD) screening to identify children with SCD at highest stroke risk combined with primary stroke prevention with chronic transfusion therapy (CTT) revolutionized pediatric sickle cell stroke management in the 1990’s. Despite the dramatic reduction of overt strokes through CTT shown in the Stroke Prevention Trial in Sickle Cell Anemia (STOP), children with SCD remain at a high risk of stroke (Figure 1).2, 9–21 Clinical and translational research in the post-STOP era have increased our understanding of the multi-factorial complexity of stroke in children with SCD (Table 1). Recent work has demonstrated how components of the cerebral metabolic rate of oxygen utilization (CMRO2) contribute to ischemia in SCD. CMRO2 is the product of cerebral blood flow (CBF), arterial oxygen content (CaO2) and oxygen extraction fraction (OEF). CBF and CaO2 comprise cerebral oxygen delivery, and OEF quantifies the transfer of available oxygen supply into the brain tissue. Ischemia occurs when CMRO2 does not meet the metabolic demands and falls below the threshold of tissue viability.26 Here, we will review advances in causal pathways of ischemic stroke and therapy options. Open in a separate window Figure 1: Stroke Event Rates as reported in the literature. SCD = Sickle Cell Disease. TCD = Transcranial Doppler CTT = Chronic Transfusion Therapy

Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans

The cerebral metabolic rate of oxygen (CMRO2) is reduced during apnea that yields profound hypoxia and hypercapnia. In this study, to dissociate the impact of hypoxia and hypercapnia on the reduction in CMRO2, 11 breath-hold competitors completed three apneas under: (a) normal conditions (NM), yielding severe hypercapnia and hypoxemia, (b) with prior hyperventilation (HV), yielding severe hypoxemia only, and (c) with prior 100% oxygen breathing (HX), yielding the greatest level of hypercapnia, but in the absence of hypoxemia. The CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Secondary measures included net-cerebral glucose/lactate exchange and nonoxidative metabolism. Reductions in CMRO2 were largest in the HX condition (−44 ± 15%, p < 0.05), with the most severe hypercapnia (PaCO2 = 58 ± 5 mmHg) but maintained oxygen saturation. The CMRO2 was reduced by 24 ± 27% in NM (p = 0.05), but unchanged in the HV apnea where hypercapnia was absent. A net-cerebral lactate release was observed at the end of apnea in the HV and NM condition, but not in the HX apnea (main effect p < 0.05). These novel data support hypercapnia/pH as a key mechanism mediating reductions in CMRO2 during apnea, and show that severe hypoxemia stimulates lactate release from the brain.

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia.

The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3min36s to 7min26s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery-jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non-oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia-induced oxygen-conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2 ) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea-divers performed a maximal apnoea (range 3min 36s to 7min 26s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2 was reduced by ∼29% (P<0.01, Cohen's d=1.18) near the termination of apnoea compared to baseline, although non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7mmHg), but not mild-hypercapnia (arterial CO2 tension: ∼46.3mmHg), depressed the CMRO2 (∼17%, P=0.04, Cohen's d=0.87). Similarly to the apnoea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.

Determinants of resting cerebral blood flow in sickle cell disease.

Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r(2) = 0.69, P < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. Am. J. Hematol. 91:912-917, 2016. © 2016 Wiley Periodicals, Inc.

Cerebral oxygen delivery is reduced in newborns with congenital heart disease

ObjectiveTo investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. MethodsUsing a “feed-and-sleep” approach to performing neonatal magnetic resonance imaging, we measured cerebral blood flow by using a slice prescription perpendicular to the right and left internal carotid arteries and basilar artery at the level of the clivus. We calculated brain volume by segmenting a 3-dimensional steady-state free procession acquisition of the whole brain, allowing quantification of cerebral blood flow indexed to brain volume. Cerebral oxygen delivery was calculated as the product of cerebral blood flow and preductal systemic arterial oxygen content obtained via a combination of conventional pulse oximetry and laboratory analysis of venous blood samples for hemoglobin concentration. ResultsA complete set of measurements were obtained in 32 newborns with heart disease and 31 controls. There was no difference in gestational age between the heart disease and control groups. There was no difference in cerebral blood flow compared with controls (103.5 ± 34.0 vs 119.7 ± 40.4 mL/min), whereas cerebral oxygen delivery was significantly lower in the congenital heart disease subjects (1881 ± 625.7 vs 2712 ± 915.7 mLO2/min). Ten newborns with congenital heart disease had diffuse excessive high signal intensity in their white matter and 2 had white matter injury whereas another 5 had both. ConclusionsNewborns with unrepaired cyanotic congenital heart disease have decreased cerebral oxygen delivery due to arterial desaturation. If brain growth and development are adversely affected through oxygen conformance, our findings could have clinical implications in terms of timing of surgical repair.

Elevated Cerebral Blood Oxygen Extraction in Non-Transfused Sickle Cell Disease Patients

Introduction Chronic Transfusion Therapy (CTT) has been successful in decreasing stroke frequency in patients with sickle cell disease (SCD). Despite this, indication for CTT is largely based on empirical evidence and the mechanisms by which CTT protects the brain remain unclear. CTT improves oxygen carrying capacity and lowers hemoglobin S%, but the corresponding impact on cerebral blood flow(CBF), cerebral metabolic rate (CMRO2), and oxygen extraction fraction (OEF) is unknown. Understanding the impact of these competing influences in non-transfused (NT) and chronically transfused (CT) SCD patients will inform stroke prevention. Thus, we measured CBF, CMRO2, and OEF, in NT and CT patients with SCD using magnetic resonance imaging (MRI).Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fourteen (6 NT, 8 CT) patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Complete blood count and hemoglobin electrophoresis were performed. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. CaO2 was calculated as the product of hemoglobin, SaO2 and the oxygen density of hemoglobin (1.36 ml/g). Phase contrast imaging of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via previously validated calibration curves. OEF represented the difference of SaO2 andSvO2 divided bySaO2. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for brain volume calculation using BrainSuiteñ software.Results Table 1 summarizes the results. Hemoglobin and oxygen content were well matched between transfused and non transfused SCD patients. Cerebral metabolic rate was also nearly identical in the two groups. However, CT patients exhibited 25% higher CBF than NT SCD patients, allowing them to have a normal oxygen extraction fraction ~30%. In contrast, OEF in NT SCD patients was abnormally high (37.8%), suggesting a decreased extraction reserve. Total oxygenation index (TOI) by NIRS also trended lower in NT SCD patients, consistent with the greater oxygen extraction and lower cerebral venous saturations observed. Abstract 1387. TableCTL (reference)NTCTp value (NT vs CT)Hemoglobin (g/dl)13.5 ± 1.229.7 ± 1.259.7 ± 1.05nsCaO2 (umol O2/ml)9.85 ± .996.84 ± 1.176.95 ±.71nsCMRO2 (umol O2/100g/min)193.1 ± 44.9239.7 ± 35.3238.6 ± 38.3nsCBF (ml/100g/min)70.0 ± 12.8101.5 ± 16.6127.1 ± 23.5< 0.05OEF (%)30.0 ± 7.137.8. ± 3.0629.7 ± 7.53< 0.05NIRS TOI56.0 ± 4.0948.5 ± 4.2153.5 ± 8.760.076SvO2 (%)65.6 ± 6.856.2 ± 5.267.1 ± 6.7< 0.05Discussion: Chronically transfused SCD patients achieve normal brain oxygenation metrics (SvO2, OEF, and NIRS) but require very high CBF to achieve this balance (lowering flow reserve). In contrast, NT SCD patients have smaller increases in CBF but require greater oxygen extraction to meet cerebrovascular demands (lowering extraction reserve). Hemoglobin S mediate changes in oxygen dissociation, blood viscosity, red cell deformability and microvascular damage potentially mediate these differences but their interplay is complicated and requires further study. DisclosuresCoates:novartis: Consultancy, Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria; acceleron: Consultancy, Honoraria.

Elevated Cerebral Metabolic Oxygen Consumption in Sickle Cell Disease

Introduction Stroke occurs when cerebral blood flow (CBF) is inadequate to the metabolic needs of the brain. In sickle cell disease (SCD) stroke is common, however accurate quantification of basal cerebral oxygen consumption (CMRO2) has not been performed. Early PET studies suggested CMRO2 was decreased in SCD patients, but these studies lacked data regarding brain volume and gray-white matter fractions; lower CMRO2 may simply have reflected brain loss from prior stroke. In contrast, NIRS and global resting energy expenditure studies have demonstrated elevated peripheral metabolic rate in SCD patients at baseline, with further increases during painful crisis. In those studies, oxygen consumption was correlated with markers of inflammation, particularly white blood cell count, consistent with metabolic consequences of neutrophil activation. Characterizing CMRO2 in SCD provides insight into better prevention and management of stroke in the SCD population. Accordingly, we measured CBF and cerebral venous saturation (SvO2) via a recently developed magnetic resonance imaging (MRI) technique: T2 Relaxation Under Spin Tagging (TRUST). Using the Fick Principle, this allowed for quantification of oxygen extraction fraction (OEF) and the first quantitative measurements of CMRO2in SCD patients.Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Fifteen patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. TRUST was used to measured T2 relaxation of blood within the sagittal sinus; T2 relaxation was converted to SvO2 using established calibration curves. OEF represented the difference of SaO2 andSvO2 .Phase Contrast (PC) of the carotid and vertebral arteries was used to measure global CBF. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for grey-white segmentation and brain volume calculations using BrainSuiteñ software. Relative grey matter CMRO2 and white matterCMRO2 were estimated by assuming that (gm) CMRO2 was three-fold higher than (wm) CRMRO2. Complete blood count, cell free hemoglobin, LDH, and hemoglobin electrophoresis were measured at the study visit.Results Table 1 summarizes the results. To compensate for their chronic anemia, SCD patients had 67% greater CBF than control subjects, producing a normal SvO2 and OEF. Oxygen delivery also trended higher than for controls leading to higher total CMRO2 in the SCD patients. CMRO2 increases remained significant even after correction for differences in grey and white matter volumes. We found no correlation between WBC and CMRO2when tested by population.Discussion Our study demonstrates elevated cerebral metabolism in SCD, mirroring increases in global resting energy expenditure and peripheral metabolic rate described by other groups. The etiology of the increased CMRO2 is unknown but could reflect neuroinflammation or energy demands from chronic injury/repair. Regardless, our observation at least partially explains the increase of CBF beyond predicted by anemia alone. By excluding patients with overt stroke and by correcting for differences in brain volume and composition, our results are the first CMRO2 measurements in SCD that are unconfounded by brain volume loss. Given the age differences between our study and control populations, we cannot exclude developmental differences in CMRO2 among patients and controls. However, in general, CMRO2 increases with age, which would tend to lessen rather than increase the CMRO2 differences seen in our study.Table 1ControlsSCDpAge (years)37.2 + 2.820.3 + 2.6<0.05Sex9 F, 3 M9 F, 6 MnsHemoglobin (g/dl)13.5 + 1.29.6 + 1.1<0.05WBC (103/uL)6.1 + 2.211.0 + 4.2<0.05Sa O2 (%)95.7 + 1.594.1 + 4.1nsSv O2 (%)65.6 + 6.763.6 + 8.4nsOEF30.0 + 7.132.3 + 7.4nsCBF (ml/100g/min)70.0 + 4.6116.8 + 19.1<0.05Cerebral O2 delivery (umol O2/100g/min)193.0 + 44.9239.0 + 35.7nsGrey Matter Mass (ml)499.6 + 72.0528.4 + 58.1nsWhite Matter Mass (ml)444.6 + 58.2422.9 + 59.5nsCMRO2 (umol O2/100g/min)193.1 + 44.9239.0 + 35.7<0.05(gm)CMRO2250.7 + 58.7292.7 + 39.7<0.05(wm) CMRO2175.5 + 41.1204.9 + 27.8<0.05 DisclosuresCoates:Novartis: Honoraria, Speakers Bureau; Apo Pharma: Consultancy, Honoraria; Acceleron: Consultancy, Honoraria; SHire: Consultancy, Honoraria.

Abstract WP49: Defining the Acute Infarct Core with CT Perfusion in Ischemic Stroke: Physiological and Technical Issues

Background: CT Perfusion (CTP) defined hemodynamic parameters used to delineate admission infarct core can be affected by truncated data acquisition, recanalization status and reactive hyperemia. We determined the optimal CTP parameter for infarct demarcation while taking these variables into account. Methods: 30 patients had CTP/NCCT scanning within 6 hours of ictus, a 24 hour CTA and an NCCT at 3 months post stroke to define final infarct. Patients were analyzed according to: 1) the percent wash out (truncation) of the ischemic time density curve (ITDC) and 2) recanalization status defined using the 24 hour CTA. CTP functional maps were generated using delay insensitive CTP software (GE Healthcare). For all patients, the total ischemic lesion (infarct+penumbra+benign oligemia) was defined using the contrast delay plus mean transit time map. Cerebral blood flow (CBF), cerebral blood volume (CBV) and the product of CBF and CBV (CBFxCBV) were used to define the infarct core defect, according to established thresholds, and compared with the infarct volume defined on the 3 month NCCT. The coefficients of correlation (R2) of linear regression models were used for the comparisons. Results: R2 values for admission CBF, CBV, and CBFxCBV defect versus final infarct volume for patients with and without truncation of the ITDC were 0.89, 0.49, 0.65 and 0.90, 0.42, 0.68, respectively; while R2 values for patients with and without recanalization at 24 hours were 0.73, 0.33, 0.44 and 0.84, 0.54, 0.45, respectively. In addition, for the recanalization group with and without truncation of the ITDC, R2 for CBF, CBV, CBFxCBV versus final infarct volume were 0.73, 0.12, 0.31 and 0.79, 0.58, 0.56, respectively. Hyperemia, defined as an increase in CBV relative to the contralateral hemisphere, was observed in 30% of patients. Both hyperemia and ITDC truncation led to poor correlation between the CBV defect and NCCT defined infarct volume. Conclusion: CBF is the optimal parameter for determining the size of the acute infarct core as it is not affected by truncation of the ITDC and autoregulatory vasodilation causing reactive hyperemia.

Effects of morphine and naloxone on cerebral blood flow and metabolism in experimental subarachnoid hemorrhage.

Naloxone is reported to improve the clinical condition of patients with subarachnoid hemorrhage (SAH). If this effect is vascular determined is unknown, wherefore the influence of morphine and naloxone on cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) after SAH was evaluated. Two groups of 8 rats each with SAH and 2 corresponding groups of controls were investigated. CBF was calculated by the intracarotid 133Xenon method and CMRO2 as the product of CBF and the difference between systemic arterial and cerebral venous oxygen content. In controls morphine, 1 mg/kg administered intravenously, decreased CBF by 25% (P < 0.001) without changing the CBF/CMRO2 ratio. In animals with SAH CBF was decreased by 32% (P < 0.001) and CBF/CMRO2 ratio by 38% (P < 0.01). Naloxone, 40 micrograms/kg administered intravenously neither influenced CBF nor the CBF/CMRO2 ratio in the 2 groups. The reported clinical effect of naloxone after SAH can, according to our results, not be explained by changing the relationship between CBF and metabolism.

Ultrasonographic measurement of cerebral blood flow, cerebral circulation time and cerebral blood volume in vascular and Alzheimer’s dementia

Vascular dementia (VD) and Alzheimer's dementia (AD) are the most common differential diagnoses in patients with cognitive impairment. Although of different etiology, small vessel disease is postulated to be present in both conditions. We investigated global cerebral blood flow (CBF), global cerebral circulation time (CCT) and global cerebral blood volume (CBV) in VD and AD patients using a multimodal ultrasound (US) approach. 20 VD and 20 AD patients were included and compared with 12 age-matched controls. Duplex US of both internal carotid and vertebral arteries was performed to measure CBF. CCT was defined as the time delay of an echo-contrast bolus arrival between the internal carotid artery and internal jugular vein using extracranial Doppler. CBV was calculated as the product of CBF and CCT. CBF was significantly lower (VD: 570 +/- 61; AD: 578 +/- 77; controls: 733 +/- 54 ml/min) and CCT significantly longer (8.8 +/- 2.6; 8.2 +/- 1.4; 6.4 +/- 0.8 s) in both patient groups compared with controls (p < 0.003). No difference in CBF and CCT was found between the two patient groups. CBV was similar in all three groups (82 +/- 20; 79 +/- 19; 78 +/- 9 ml). The equally reduced CBF and prolonged CCT in VD and AD support the hypothesis, that small vessel disease is a relevant factor in both types of dementia. The presented multimodal US approach helps to assess the extent of changes in the global cerebral hemodynamics in patients with dementia but does not allow a differentiation between VD and AD.

Brain oxygen utilization is unchanged by hypoglycemia in normal humans: lactate, alanine, and leucine uptake are not sufficient to offset energy deficit

During hypoglycemia, substrates other than glucose have been suggested to serve as alternate neural fuels. We evaluated brain uptake of endogenously produced lactate, alanine, and leucine at euglycemia and during insulin-induced hypoglycemia in 17 normal subjects. Cross-brain arteriovenous differences for plasma glucose, lactate, alanine, leucine, and oxygen content were quantitated. Cerebral blood flow (CBF) was measured by Fick methodology using N(2)O as the dilution indicator gas. Substrate uptake was measured as the product of CBF and the arteriovenous concentration difference. As arterial glucose concentration fell, cerebral oxygen utilization and CBF remained unchanged. Brain glucose uptake (BGU) decreased from 36.3+/-2.6 to 26.6+/-2.1 micromol.100 g of brain(-1).min(-1) (P<0.001), equivalent to a drop in ATP of 291 micromol.100 g(-1).min(-1). Arterial lactate rose (P<0.001), whereas arterial alanine and leucine fell (P<0.009 and P<0.001, respectively). Brain lactate uptake (BLU) increased from a net release of -1.8+/- 0.6 to a net uptake of 2.5+/-1.2 micromol.100 g(-1).min(-1) (P<0.001), equivalent to an increase in ATP of 74 micromol.100 g(-1).min(-1). Brain leucine uptake decreased from 7.1+/-1.2 to 2.5 +/- 0.5 micromol.100 g(-1).min(-1) (P<0.001), and brain alanine uptake trended downward (P<0.08). We conclude that the ATP generated from the physiological increase in BLU during hypoglycemia accounts for no more than 25% of the brain glucose energy deficit.

Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study.

Quantitative estimates of cerebral metabolic rate of oxygen utilization using magnetic resonance imaging can have profound implications for the understanding of brain metabolic activity as well as the investigation of cerebrovascular disease. In this study, five normal volunteers were studied. All images were acquired on a Siemens 1.5 T scanner (Siemens Medical Systems Inc, Erlangen, Germany). Cerebral blood flow (CBF) was obtained in vivo with a dynamic imaging approach and the acquired images were post-processed with the singular value decomposition method (SVD). In addition, a multi-echo gradient echo/spin echo sequence was employed to provide MR estimates of oxygen extraction fraction (MR_OEF) in vivo. Subsequently, an absolute measure of MR cerebral metabolic rate of oxygen utilization (MR_CMRO(2)) was obtained in all subjects by taking the product of CBF and MR_OEF. A mean MR_CMRO(2) of 28.94 +/- 3.26 ml/min/100 g and 12.57 +/- 3.11 ml/min/100 g was obtained for gray matter and white matter, respectively, suggesting that the gray matter utilizes more oxygen than white matter under normal physiological conditions. These results yield a gray matter to white matter CMRO(2) ratio of 2.37 +/- 0.37, which is comparable to the reported values in the literature. More studies are needed to further improve on the accuracy as well as shortening the required data acquisition time so that the proposed approaches can be utilized in a routine clinical setting.

Inhibition of cerebral metabolic and circulatory responses to nitrous oxide by 6-hydroxydopamine in dogs.

To determine whether cerebral metabolic and circulatory consequences of N2O result from activation of the sympathoadrenal system. The effects of pretreatment with intracisternal injection of 6-OHDA, which produces chemical sympathectomy, were studied in dogs. Seven days before measurement dogs were pretreated with intracisternal injection of either saline vehicle (sham-group) or 100 micrograms.kg-1 6-hydroxydopamine (6-OHDA, group). Cerebral blood flow (CBF) was measured using an electromagnetic flow-meter probe and cerebral metabolic rate for oxygen (CMRO2) was calculated as the product of CBF and arterial-sagittal sinus blood oxygen content difference [C(a-v)O2]. In the sham group, N2O (60%) increased CMRO2 from 6.11 +/- 0.21 ml.100 g-1.min-1 to 7.10 +/- 0.39 ml.100 g-1.min-1 and CBF from 63 +/- 5 ml.100 g-1.min-1 to 173 +/- 26 ml.100 g-1.min-1. In the 6-OHDA group, CMRO2, did not change during N2O exposure, whereas CBF increased from 61 +/- 3 ml.100 g-1.min-1 to 135 +/- 19 ml.100 g-1.min-1 but less then in the sham group. The 6-OHDA group displayed a reduction in cortical noradrenaline (NA) concentration from 263.2 +/- 35.6 ng.g-1 to 102.7 +/- 16.5 ng.g-1. Cortical dopamine (DA) concentration was not affected by 6-OHDA administration. These results suggest that most of the increase in CMRO2 and at least a part of the increase in CBF during N2O exposure in the sham-group are related to sympathoadrenal-stimulating effects of N2O.

Measurement of cerebral venous saturation in adults using near infrared spectroscopy.

Saturation measurements have long been used to provide information about oxygenation levels within tissue in the form of a single percentage value. Whilst the measurement of peripheral arterial oxygen saturation (SaO2) provides useful information about the delivery of oxygen to the brain, a measure of the actual level of cerebral oxygen consumption and uptake would be a more useful guide for the direction of therapies. Oxygen consumption is the product of cerebral blood flow (CBF) and the difference between arterial and venous oxygen content. Measurements of cerebral venous saturation can therefore be used as an indicator of oxygen consumption and have been shown to be a useful clinical parameter in the management of patients with compromised cerebral haemodynamics (Garlick et al., 1987, Cruz et al., 1991).KeywordsCerebral Blood FlowCerebral Blood VolumeJugular BulbSaturation MeasurementUnited Kingdom IntroductionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow autoregulation in man

We have studied the effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2) and CBF autoregulation in 20 adult patients undergoing lumbar disc surgery. Ten patients received ketanserin and 10 isotonic saline. CBF measurements were started after 1 h of infusion of saline or ketanserin. The patients were anaesthetized with thiopentone 5 mg kg-1 followed by isoflurane. During 1 MAC of isoflurane, baseline values were recorded and then CBF autoregulation was examined (mean arterial pressure increased by about 30% with angiotensin). The sequence was repeated with 2 MAC of isoflurane. CBF was measured by the i.v. xenon-133 technique. CMRO2 was calculated as the product of CBF and the cerebral arterio-venous oxygen content difference. Ketanserin had no effect on CBF, CMRO2 or CBF autoregulation during isoflurane anaesthesia, therefore all patients were pooled for evaluation of the effect of isoflurane. Increasing isoflurane anaesthesia from 1 to 2 MAC increased mean CBF from 41 to 49 ml/100 g min-1 (P < 0.01) and decreased mean CMRO2 from 1.5 to 1.1 ml/100 g min-1 (P < 0.001) and thus abolished the coupling between flow and metabolism. The CBF autoregulation test indicated that autoregulation was disrupted at 2 MAC, but not during 1 MAC isoflurane anaesthesia.

EFFECT OF KETANSERIN ON GLOBAL CEREBRAL BLOOD FLOW AND CEREBRAL OXYGEN METABOLISM DURING MIDAZOLAM-FENTANYL OR ISOFLURANE ANAESTHESIA

We have studied the effect of ketanserin on cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2) and cerebrovascular carbon dioxide reactivity in 19 adult patients undergoing lumbar disc operation--10 during midazolam-fentanyl anaesthesia (group A) and nine during isoflurane anaesthesia (group B). Measurements were made in each patient whilst awake, during anaesthesia, during anaesthesia with ketanserin and during anaesthesia with ketanserin and hyperventilation. CBF was measured by the i.v. xenon-133 technique. CMRO2 was calculated as the product of CBF and the cerebral arterio-venous oxygen content difference. In the awake state, CBF was 52 and 51 ml/100 g min-1 and CMRO2 3.8 and 3.5 ml/100 g min-1 in groups A and B, respectively. After induction of anaesthesia, CBF decreased 37% in group A and 22% in group B (P < 0.05); CMRO2 decreased 26% in group A and 51% in group B (P < 0.05). Adding ketanserin did not change CBF or CMRO2 in either group. The carbon dioxide reactivity of the cerebral vessels during anaesthesia with ketanserin was 15.4% kPa-1 in group A and 24% kPa-1 in group B. We concluded that ketanserin, in a clinically recommended dose, administered during midazolam-fentanyl or isoflurane anaesthesia had no effect on global CBF, CMRO2 or the relationship between the two factors. Cerebrovascular carbon dioxide reactivity was preserved.