Cerebral Blood Flow Index Research Articles

Effect of sevoflurane on cerebral blood flow and cerebrovascular resistance at surgical level of anaesthesia: a transcranial Doppler study

It is widely accepted that sevoflurane affects cerebral circulation, but there are uncertainities regarding the magnitude of its effect. The aim of the present work was to assess the effect of sevoflurane on the cerebral circulation at surgical levels of anaesthesia. Twenty patients undergoing elective lumbar discectomies were investigated. Anaesthesia was induced with propofol and maintained with sevoflurane. The level of surgical anaesthesia was determined by bispectral index, the target level was 45-55. Transcranial Doppler (TCD) measurement was performed before induction and after reaching the surgical level of anaesthesia. Besides routine parameters (middle cerebral artery mean blood flow velocity (MCAV) and pulsatility index (PI)) derived parameters (estimated cerebral perfusion pressure (eCPP), cerebral blood flow index (CBFI) and resistance area product (RAP)) were calculated by taking changes of mean arterial pressure also into account. MCAV decreased from 54.1 +/- 13.3 to 43.7 +/- 18.5 cm s-1, P < 0.01 and PI increased from 0.79 +/- 0.2 to 0.92 +/- 0.2, P < 0.01 after reaching the surgical level of anaesthesia. As a result eCPP decreased by 18.2%, CBFI by 25.5% and RAP increased by 15% respectively. Our data indicate a vasodilatory effect of sevoflurane at surgical level of anaesthesia on large cerebral vessels or a vasoconstriction of the resistance arterioles likely caused by decreased brain metabolism.

Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension

We sought to determine whether cerebral autoregulation (CA) is compromised during orthostatic stress superimposed with systemic hypotension. Transient systemic hypotension was produced by deflation of thigh cuffs previously inflated to suprasystolic pressure, combined with or without lower body negative pressure (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by -8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr, respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite decreases in systolic and pulse pressures. Middle cerebral arterial blood flow velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a decrease in regional cerebral O2 saturation. However, the percent decrease in VMCA was markedly less than that of CO. This suggests that the magnitude of the change in VMCA (an index of cerebral blood flow) is less than would be predicted, given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/-2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Likewise, this acute hypotension resulted in decreases in VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2 saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values following transient hypotension (ranging from 5 to 8 s) occurred significantly earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope during acute hypotension. We conclude that CA is preserved during LBNP, superimposed with transient systemic hypotension, despite the decrease in VMCA associated with sustained central hypovolemia in normal healthy individuals. This preserved CA is vital for the prevention of orthostatic syncope.

Control of end-tidal PCO 2 reduces middle cerebral artery blood velocity variability: Implications for physiological neuroimaging

Breath-by-breath variability of the end-tidal partial pressure of CO 2 (P et CO 2 ) has been shown to be associated with cerebral blood flow (CBF) fluctuations. These fluctuations can impact neuroimaging techniques that depend on cerebrovascular blood flow. We hypothesized that controlling P et CO 2 would reduce CBF variability. Dynamic end-tidal forcing was used to control P et CO 2 at 1.5 mm Hg above the resting level and to hold the end-tidal partial pressure of oxygen (P et O 2 ) at the resting level. Peak blood velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler ultrasound (TCD) as an index of CBF. Blood velocity parameters and timing features were determined on each waveform and the variance of these parameters was compared between Normal (air breathing) and Forcing (end-tidal gas control) sessions. The variability of all velocity parameters was significantly reduced in the Forcing session. In particular, the variability of the average velocity over the cardiac cycle was decreased by 18.2% ( P < 0.001). For the most part, the variability of the timing parameters was unchanged. Thus, we conclude that controlling P et CO 2 is effective in reducing CBF variability, which would have important implications for physiologic neuroimaging.

CIRCADIAN PREFERENCE AND COGNITIVE FUNCTIONING AMONG REHABILITATION INPATIENTS

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n = 28) and noncognitive (n = 28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta2 .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e.g., complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, an index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.

Clinical and imaging predictors of intracerebral haemorrhage in stroke patients treated with intravenous tissue plasminogen activator

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients. Methods: 48 consecutive patients with hemispheric stroke...

Availability of N-isopropyl- p-[ 125I]iodoamphetamine (IMP) as a practical cerebral blood flow (CBF) indicator in rats

Since a very complicated technique is necessary to measure cerebral blood flow (CBF) with [ 14C]iodoantipyrine in small animals, a practical and easy method is needed. In this paper, the differential uptake ratio (DUR) at 5 min after injection of N-isopropyl- p-[ 125I]iodoamphetamine (IMP) was estimated as an index of CBF in normal rats and compared with the quantitative CBF value measured using [ 15O]H 2O and dynamic PET scan. A good correlation between the two values was obtained. The results indicate that DUR of [ 125I]IMP at 5 min after injection in rats is a useful and practical indicator of CBF since neither arterial blood sampling nor metabolite correction is necessary.

Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness

Nocturnal hypoxia is a major pathological factor associated with cardiorespiratory disease. During wakefulness, a decrease in arterial O2 tension results in a decrease in cerebral vascular tone and a consequent increase in cerebral blood flow; however, the cerebral vascular response to hypoxia during sleep is unknown. In the present study, we determined the cerebral vascular reactivity to isocapnic hypoxia during wakefulness and during stage 3/4 non-rapid eye movement (NREM) sleep. In 13 healthy individuals, left middle cerebral artery velocity (MCAV) was measured with the use of transcranial Doppler ultrasound as an index of cerebral blood flow. During wakefulness, in response to isocapnic hypoxia (arterial O2 saturation -10%), the mean (+/-SE) MCAV increased by 12.9 +/- 2.2% (P < 0.001); during NREM sleep, isocapnic hypoxia was associated with a -7.4 +/- 1.6% reduction in MCAV (P <0.001). Mean arterial blood pressure was unaffected by isocapnic hypoxia (P >0.05); R-R interval decreased similarly in response to isocapnic hypoxia during wakefulness (-21.9 +/- 10.4%; P <0.001) and sleep (-20.5 +/- 8.5%; P <0.001). The failure of the cerebral vasculature to react to hypoxia during sleep suggests a major state-dependent vulnerability associated with the control of the cerebral circulation and may contribute to the pathophysiologies of stroke and sleep apnea.

Microsphere‐induced embolic stroke: An MRI study

Despite the many studies of the middle cerebral artery occlusion (MCAO) model, efficient therapy for stroke is still lacking, emphasizing the need for further development and characterization of experimental stroke models. In the present study, the rather unexplored multifocal microsphere-induced stroke model in rats was characterized by multiparametric MRI. We induced microembolic infarction in a group of Sprague-Dawley rats by injecting a dose of about 1000 50-microm polyethylene microspheres intracranially from the external carotid artery. Diffusion-, perfusion-, and T(2)-weighted MRI were used to evaluate the infarct development during and following the first 3 hr after microsphere injection (N = 20). The animals were also imaged at 12-hr (N = 8), 24-hr (N = 17), and 48-hr (N = 5) time points. After the final imaging time point, the brains were removed and sectioned into 2-mm-thick slices, and infarct volumes were measured by 2,3,4-triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion coefficient (ADC) maps, a volume of reduced ADC appeared 0.5-1.0 hr postinjection, and by the 3-hr time point the volume of ADC reduction had increased to a size of 5% +/- 1% (mean +/- SEM) of the brain hemisphere. The lesion volume increased significantly (P < 0.01) to 16% +/- 2% of the hemisphere volume at the 12-hr time point, while at 24 hr the lesion (15% +/- 2% of the hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion deficit resulting from the microsphere injection was immediate, going from a cerebral blood flow index (CBF(i)) of 74% +/- 3% at the time of microsphere injection to 68% +/- 2% of the contralateral mean at 3 hr (P < 0.05), to 55% +/- 4% of the contralateral values at 12 hr (P < 0.05), and to 57% +/- 2% of the contralateral mean at 24 hr (P < 0.001). The lesion development in the microsphere-induced stroke model was found to be slower than in the MCAO model, and continued up to the 24-48-hr time point.

Perfusion MRI of U87 brain tumors in a mouse model.

Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue:blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue. The apparent T(1) (T(1app)) was 2.01 +/- 0.06 sec for tumor core and 1.66 +/- 0.03 sec for normal tissue. The ICBF and the T(1app) values were significantly different (P < 0.001) between these two regions. The detailed changes of ICBF and T(1app) in the transition from the tumor core through the tumor periphery to surrounding tissue were studied. Immunohistochemistry indicated that tumor vascularity was not uniform, with microvessel density highest in normal brain and the tissue surrounding the tumor and lowest in the tumor core. The large difference in ICBF between the tumor core and normal tissue suggests that this index might be useful for the assessment of the efficacy of antiangiogenic therapy.

Evaluation of regional cerebral blood flow changes in panic disorder with Tc99m-HMPAO SPECT

The objective of this study is to investigate differences in regional cerebral blood flow (rCBF) and rCBF asymmetry index values between panic disorder patients ( n=22) and normal comparison subjects ( n=19) using Tc99m-hexamethylpropyleneamine oxime single photon emission tomography imaging. A decrease in perfusion in the bilateral frontal regions and a relative increase in perfusion in the right medial and superior frontal regions were found. There were significant positive correlations between scores on the Panic and Agoraphobia Scale and rCBF asymmetry index values of the parietal, superior temporal and lateral temporal regions in the panic disorder patients. These correlations point to a relationship between the severity of panic disorder and relative right brain activation. Activation of the amygdala, increased CBF in the frontal region, or hyperactivation of the locus ceruleus seen in panic disorder may explain the decrease in the rCBF in the inferior frontal region.

The effect of isosorbide dinitrate, a donor of nitric oxide, on maternal cerebral blood flow in gestational hypertension and preeclampsia

Objective: The purpose of this study was to investigate the effect of a nitric oxide donor on cerebral perfusion pressure and other blood flow index values in the maternal middle cerebral and basilar arteries. Study Design: Sublingual tablets of 5-mg isosorbide dinitrate were administered to 19 hypertensive pregnant patients. Doppler velocimetry of the middle cerebral and basilar arteries was obtained with a transcranial Doppler with the use of the transtemporal and suboccipital approach. Results: The mean (±SEM) flow velocity in the middle cerebral artery significantly decreased from a baseline of 65.9 ± 3.1 cm/s to 55.2 ± 2.2 and 52.0 ± 2.1 cm/s at 10 and 20 minutes (P <.0001). Resistance area product insignificantly increased from a baseline of 2.0 ± 0.1 before isosorbide dinitrate to 2.19 ± 0.11 at 20 minutes. No significant changes were observed in the resistance and pulsatility indices in the middle cerebral artery. The cerebral perfusion pressure did not change significantly after isosorbide dinitrate (84.5 ± 7.3, 80.8 ± 6.6, and 78.5 ± 5.0 mm Hg at 0, 10, and 20 minutes, respectively) nor did the cerebral blood flow index. Conclusion: The results obtained demonstrate that cerebral perfusion pressure is unaltered by isosorbide dinitrate, despite significant changes in maternal blood pressure and in blood flow velocities in the middle cerebral artery.

Cerebral blood flow index image as a simple indicator for the fate of acute ischemic lesion.

To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, we attempted to investigate 1) whether CBF index images can reveal the resulting infracted area, 2) whether the CBF index can correlate other modality (SPECT). DWI and DPI were obtained in 17 patients within 12 hours of stroke onset and follow up MRI. On three DPI delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, correlations between initial lesion volume of and follow up infarction volume of three images and rCBF images delivered with singular value decomposition (SVD) methods were assessed. Then 99mTc-ECD SPECT was taken immediately after MRI to correlate to MRI data. Among the three images, lesion volume of CBF index images against follow up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) and had identical accuracy to the regression coefficient of rCBF images. CBF index well correlated to SPECT delivered CBF. CBF index images can accurately predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

Normocapnia improves cerebral oxygen delivery during conventional oxygen therapy in carbon monoxide–exposed research subjects

Study objective: We determine whether maintaining normocapnia during hyperoxic treatment of carbon monoxide–exposed research subjects improves cerebral oxygen delivery. Methods: This experiment used a randomized, single-blinded, crossover design. We exposed 14 human research subjects to carbon monoxide until their carboxyhemoglobin levels reached 10% to 12%. We then treated each research subject with 60 minutes of hyperoxia with or without normocapnia. Research subjects returned after at least 24 hours, were reexposed to carbon monoxide, and were given the alternate treatment. Relative changes in cerebral oxygen delivery were calculated as the product of blood oxygen content and middle cerebral artery velocity (an index of cerebral blood flow) as measured by transcranial Doppler ultrasonography. Results: Maintaining normocapnia during hyperoxic treatment resulted in significantly higher cerebral oxygen delivery compared with standard oxygen treatment (P <.05; 95% confidence interval at 60 minutes 2.8% to 16.7%) as a result of the prevention of hypocapnia-induced cerebral vasoconstriction and more rapid elimination of carbon monoxide due to increased minute ventilation. Conclusion: If severely poisoned patients respond like our research subjects, maintaining normocapnia during initial hyperoxic treatment of carbon monoxide poisoning may lead to increased oxygen delivery to the brain. Determining the effect of such a change in conventional treatment on outcome requires clinical studies. [Ann Emerg Med. 2002;40:611-618.]

Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model.

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after stroke increases risk of hemorrhagic transformation, particularly in areas with blood-brain barrier leakage. Our aim was to characterize acute effects of rtPA administration on the integrity of microvascular barriers. Stroke was induced in spontaneously hypertensive rats by unilateral embolic middle cerebral artery occlusion. Six hours after stroke, rtPA was intravenously administered (n=10). Controls received saline (n=4). Extravasation of the large-diameter contrast agent monocrystalline iron oxide nanocolloid (MION) was assessed with susceptibility contrast-enhanced MRI during rtPA injection. In addition, we performed perfusion MRI and diffusion-weighted MRI. After MRI, 2 hours after rtPA treatment, intracerebral hemorrhage was quantified with a spectrophotometric hemoglobin assay. Late rtPA treatment resulted in increased hemorrhage volume (8.4+/-1.7 versus 2.9+/-0.9 micro L in controls; P<0.05). In MION-injected animals, during rtPA administration, transverse relaxation rate change (DeltaR2*) increased from 12.4+/-6.0 to 31.6+/-19.2 s(-1) (P<0.05) in areas with subsequent hemorrhage. Significant DeltaR2* changes were absent in nonhemorrhagic areas, in animals without injected MION, and in saline-treated animals. Thrombolytic therapy did not improve perfusion in regions with hemorrhagic transformation (cerebral blood flow index was 22.8+/-19.7% [of contralateral] at 0.5 hours before and 22.4+/-18.0% at 1 hour after rtPA administration). The DeltaR2* changes during rtPA delivery in MION-injected animals indicate extravasation of MION, which reflects increased permeability of the blood-brain barrier. This implies that late rtPA treatment rapidly aggravates early ischemia-induced damage to microvascular barriers, thereby enhancing hemorrhagic transformation.

Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas.

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant ( p<0.0005) lower rrCBV and rrCBFi. The edema index (EI) correlated strongly with the rrCBV. A fitting procedure resulted into the following mathematical relation: EI=0.1/rrCBV(2). The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10(-3) vs 1.55 x 10(-3) mm(2)/s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema.

654 The effect of isosorbide dinitrate, a donor of nitric oxide, on middle cerebral artery blood flow indices in preeclamptic patients

654 The effect of isosorbide dinitrate, a donor of nitric oxide, on middle cerebral artery blood flow indices in preeclamptic patients

Increased cerebral blood flow and cardiac output following cerebral arterial air embolism in sheep.

1. The effects of cerebral arterial gas embolism on cerebral blood flow and systemic cardiovascular parameters were assessed in anaesthetized sheep. 2. Six sheep received a 2.5 mL injection of air simultaneously into each common carotid artery over 5 s. Mean arterial blood pressure, heart rate, end-tidal carbon dioxide and an ultrasonic Doppler index of cerebral blood flow were monitored continuously. Cardiac output was determined by periodic thermodilution. 3. Intracarotid injection of air produced an immediate drop in mean cerebral blood flow. This drop was transient and mean cerebral blood flow subsequently increased to 151% before declining slowly to baseline. Coincident with the increased cerebral blood flow was a sustained increase in mean cardiac output to 161% of baseline. Mean arterial blood pressure, heart rate and end-tidal carbon dioxide were not significantly altered by the intracarotid injection of air. 4. The increased cardiac output is a pathological response to impact of arterial air bubbles on the brain, possibly the brainstem. The increased cerebral blood flow is probably the result of the increased cardiac output and dilation of cerebral resistance vessels caused by the passage of air bubbles.

Tissue Viability Thresholds in Acute Stroke

Tissue Viability Thresholds in Acute Stroke

Delayed rt-PA treatment in a rat embolic stroke model: diagnosis and prognosis of ischemic injury and hemorrhagic transformation with magnetic resonance imaging.

The authors characterized effects of late recombinant tissue plasminogen activator (rt-PA) administration in a rat embolic stroke model with magnetic resonance imaging (MRI), to assess potential MRI correlates, or predictors, or both, of rt-PA-induced hemorrhage. Diffusion-, perfusion-, and postcontrast T1-weighted MRI were performed between 4 and 9 hours and at 24 hours after embolic stroke in spontaneously hypertensive rats. Treatment with either rt-PA or saline was started 6 hours after stroke. A spectrophotometric hemoglobin assay quantified hemorrhage severity. Before treatment, relative cerebral blood flow index (rCBFi) and apparent diffusion coefficient (ADC) in the ischemic territory were 30% +/- 23% and 60% +/- 5% (of contralateral), respectively, which increased to 45% +/- 39% and 68% +/- 4% 2 hours after rt-PA. After 24 hours, rCBFi and ADC were 27% +/- 27% and 59 +/- 5%. Hemorrhage volume after 24 hours was significantly greater in rt-PA-treated animals than in controls (8.7 +/- 3.7 microL vs. 5.1 +/- 2.4 microL, P < 0.05). Before rt-PA administration, clear postcontrast T1-weighted signal intensity enhancement was evident in areas of subsequent bleeding. These areas had lower rCBFi levels than regions without hemorrhage (23% +/- 22% vs. 36% +/- 29%, P < 0.05). In conclusion, late thrombolytic therapy does not necessarily lead to successful reperfusion. Hemorrhage emerged in areas with relatively low perfusion levels and early blood-brain barrier damage. Magnetic resonance imaging may be useful for quantifying effects of thrombolytic therapy and predicting risks of hemorrhagic transformation.

Assessment of cerebral hemodynamics during roll over test in healthy pregnant women and those with pre-eclampsia

Objective To compare cerebral autoregulatory responses obtained during roll over tests in healthy pregnant women and those with pre-eclampsia in order to assess the middle cerebral artery velocity changes in relation to the roll over test in normotensive and pre-eclamptic women. Participants Twenty-two healthy pregnant women and 26 with pre-eclampsia underwent transcranial Doppler measurements of the middle cerebral artery. Methods Systolic, mean and diastolic blood flow velocities and mean arterial blood pressures were recorded in the left lateral position and five minutes after turning to the supine position. Absolute values of mean blood flow velocities, mean arterial blood pressure values and calculated cerebral blood flow indices as well as cerebrovascular resistance area products were compared at different positions among the groups. Results Mean arterial blood pressure increased in both groups while turning from the left lateral to the supine position. In women with pre-eclampsia both mean arterial blood pressure and absolute values of mean blood flow velocity values were higher in both positions, compared with healthy pregnant women. In both groups, changing the position resulted in a decrease of absolute values of mean blood flow velocities. Calculated cerebral blood flow indices did not change, while cerebrovascular resistance area products increased significantly in the groups during roll over testing. In women with pre-eclampsia, the increase of cerebrovascular resistance area products was more pronounced as compared with healthy pregnant women. Conclusions In women with pre-eclampsia roll over test results in an increase of the mean arterial blood pressure, which is accompanied by a decreased mean blood flow velocity in the middle cerebral artery. Further studies are needed to clarify the pathophysiological background of cerebral haemodynamic changes in pre-eclampsia.