Cerebral Blood Flow Estimates Research Articles

Magnetic resonance assessment of cerebral perfusion in depressed cardiac patients: preliminary findings.

The authors investigated the links between depression, cardiac disease, and microcirculatory cerebral blood flow (CBF). A magnetic resonance imaging technique based on arterial spin tagging was used to estimate microcirculatory CBF in depressed (N = 5) and comparison (N = 14) elderly subjects with coronary artery disease. Signal intensity ratios corresponding to relative microcirculatory CBF were calculated for four regions on two axial images through the upper and lower halves of the lateral ventricles. On the superior image, estimates of microcirculatory CBF were statistically significantly lower on the left side in the depressed subjects than in the nondepressed group. When the ratios in the superior and inferior images were averaged, the depressed subjects had lower values for both left periventricular regions of interest and the parietal region. Despite the small study group and indirect estimates of blood flow, these preliminary findings suggest that a relative cerebral hypoperfusion may underlie depression in elderly cardiac patients.

Statistical method for the estimation of cerebral blood flow using the Kety–Schmidt technique

The Kety-Schmidt technique for the measurement of cerebral blood flow (CBF) has been in use for many years, but efficient statistical methods for producing estimates of CBF have received little attention. This paper proposes simple statistical models for this problem and explores their properties using data from a recent study of severe head injury in children. The method, which can readily be implemented on a personal computer, allows the uncertainty in the estimate of CBF to be quantified.

Agreement between ultrasonic Doppler venous outflow and Kety and Schmidt estimates of cerebral blood flow.

1. The present study compares the indirect Fick nitrous oxide equilibration method of Kety and Schmidt for cerebral blood flow (CBF) estimation with a direct ultrasonic Doppler index of venous outflow. 2. Cerebral blood flow was determined simultaneously by the direct measurement of sagittal sinus blood velocity and the indirect Kety and Schmidt method in five anaesthetized sheep during high and low steady states of CBF. High- and low-flow states were achieved by altering ventilation to produce hypercarbia and hypocarbia, respectively. 3. Four different sets of calculations were used to make the Kety and Schmidt estimations: arterial-venous nitrous oxide concentration differences during uptake or elution of the indicator and with or without extrapolation of arterial-venous differences to infinity. 4. During 15 min nitrous oxide administration, apparent blood:tissue equilibration of nitrous oxide was rapid in some data sets and slow in others. 5. There were no significant differences in CBF estimates between any of the four Kety and Schmidt calculations or the direct ultrasonic Doppler venous outflow method; however, CBF estimates based on nitrous oxide uptake correlated more strongly with the direct method than estimates based on nitrous oxide elution. 6. In the high-flow state, CBF estimates based on nitrous oxide uptake, but not those based on elution, distinguished between rapid and slow blood:tissue equilibration of nitrous oxide. 7. This provides validation of the Doppler sheep brain venous outflow method against the widely used Kety and Schmidt method.

Correlation of flow probe determinations of common carotid artery blood flow and internal carotid artery blood flow with microsphere determinations of cerebral blood flow in piglets.

We investigated whether blood flow determined by a flow probe situated on one common carotid artery provided an accurate estimation of unilateral cerebral blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated piglets, blood flow determined by an ultrasonic flow probe placed on the right common carotid artery was correlated with CBF determined by microspheres under two experimental conditions: 1) before ligation of the right external carotid artery with both the right external and internal carotid circulations intact [common carotid artery blood flow (CCABF) condition], and 2) after ligation of the right external carotid artery (ipsilateral to the flow probe) with all residual right-sided carotid artery blood flow directed through the right internal carotid artery [internal carotid artery blood flow (ICABF) condition]. The left carotid artery was not manipulated in any way in either protocol. Independent correlations of unilateral CCABF and ICABF with microsphere-determined unilateral CBF were highly significant over a 5-fold range of CBF induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p < 0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF was 1.68 +/- 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The slope of the correlation of unilateral ICABF versus unilateral CBF did not differ significantly from unity (1.06 +/- 0.15), and the y intercept did not differ significantly from zero [-1.3 +/- 5.2 (SEM) mL]. Consequently, unilateral ICABF determined by flow probe accurately reflected unilateral CBF determined by microspheres under these conditions. Flow probe assessments of CCABF and ICABF in piglets may provide information about dynamic aspects of vascular control in the cerebral circulation that has heretofore been unavailable.

Rapid algorithms for the construction of cerebral blood flow and oxygen utilization images with oxygen-15 and dynamic positron emission tomography

Two rapid estimation algorithms for construction of cerebral blood flow (CBF) and oxygen utilization (CMRO) images with dynamic positron emission tomography (PET) are presented. These algorithms are based on the linear least squares (LLS) and generalized linear least squares (GLLS) methodologies. Using the conventional two-compartmental model and multiple tracer studies, we derived a linear relationship for brain tissue activity to arterial blood activity, time-integrated arterial blood activity and time-integrated brain tissue activity. The LLS technique is computationally efficient as no regression analysis is required, while GLLS is used to refine the estimates obtained from LLS. A comparative study using non-linear least squares regression (NLS) revealed excellent correlation between the new algorithms for various noise levels expected in clinical applications. A sensitivity analysis was performed to examine reliability and identifiability of the parameter estimates. In view of the results, LLS and GLLS provide rapid and reliable estimates of CBF and CMRO when applied to dynamic PET data. These algorithms are particularly suitable for pixel-by-pixel construction of high resolution and highly accurate PET functional images.

Variation in cerebral perfusion pressure with different hypertensive states in pregnancy

Objective: Our purpose was to compare the estimated maternal cerebral perfusion pressure and an index of vascular resistance, the resistance area product, in nonpregnant women with hypertensive pregnant women. Study Design: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasonography in 17 nonpregnant women, 17 pregnant normotensive patients, 20 pregnant patients with chronic hypertension, and 21 pregnant patients with pre-eclampsia (defined by The American College of Obstetricians and Gynecologists criteria) and cerebral blood flow velocities were determined. We calculated estimated cerebral perfusion pressure as [Estimated cerebral perfusion pressure = V mean/(V mean = V diastolic) (Mean blood pressure – Diastolic blood pressure)] modified from Aaslid et al, 1986. Because the diameter of the vessels could not be measured directly, an index of resistance, the resistance area product, was calculated. Resistance area product = Mean blood pressure/mean velocity (Evans et al, 1988). We calculated an index of cerebral blood flow (Cerebral blood flow index) = Estimated cerebral perfusion pressure/resistance area product. Results: Women who were chronically hypertensive and those with pre-eclampsia showed a significant increase in estimated cerebral perfusion pressure and resistance area product compared with nonpregnant and pregnant normotensive women. An estimate of cerebral blood flow (cerebral blood flow index) in nonpregnant women showed that pregnancy resulted in a nonsignificant 18% increase in cerebral blood flow. Conclusions: Women with chronic hypertension and pre-eclampsia behave similarly by demonstrating significant increases in cerebral perfusion pressure (estimated cerebral perfusion pressure) and cerebrovascular resistance (resistance area product) compared with normotensive and nonpregnant women. Pregnant patients have a minimal increase in cerebral blood flow (18%). (Am J Obstet Gynecol 1998;179:1200-3.)

In vivo estimation of cerebral blood flow, oxygen consumption and glucose metabolism in the pig by [ 15O]water injection, [ 15O]oxygen inhalation and dual injections of [ 18F]fluorodeoxyglucose

There is a need for suitable non-primate laboratory animals for studies of brain function by positron emission tomography (PET). To provide a comparative index of the circulatory physiology of the pig, we have applied novel PET tracer methodology to seven anaesthetized pigs, and measured cerebral regional oxygen consumption (CMR O 2 ), cerebral blood flow (CBF), and cerebral glucose metabolism (CMR glc). Blood flow and flow-metabolism couple were estimated for selected cerebral regions of interest. We found an average hemispheric CMR O 2 of 171±18 μmol/100 cm 3/min. Individual hemispheric CBF measurements varied between 33 and 41 ml/100 cm 3/min, with an average of 37±3 ml/100 cm 3/min at an average Pa CO 2 of 4.3±0.9 kPa. The blood flow dependency on arterial P CO 2 was calculated from the results of the carbon dioxide response in two pigs in which the CBF measurements obeyed the equation CBF (ml/100 cm 3/min)=8.9 Pa CO 2 (kPa). In each pig, CMR glc was studied twice with a double-injection FDG method. In the first session, the values of CMR glc averaged 27±3 and 23±4 μmol/100 cm 3/min, estimated by multilinear and linear regression analysis, respectively. In the second session, the corresponding averages were 27±3 and 24±3 μmol/100 cm 3/min, respectively. The average oxygen extraction fraction was 0.46±0.09 and the oxygen-glucose ratio was 6.1±0.8. The findings indicate that the pig is suitable for PET studies of cerebral blood flow, cerebral oxygen consumption and glucose metabolism.

Monitoring the central nervous system

While clinical examination represents the gold standard for monitoring of central nervous system (CNS) function, this is usually inaccessible during the perioperative period and critical illness. Bedside monitoring of the CNS in these circumstances should include measurement of cerebral perfusion pressure, estimation of cerebral blood flow, assessment of cerebral oxygenation, and assessment of CNS electrical activity. Useful techniques include intracranial pressure monitoring, transcranial Doppler ultrasound, jugular bulb oximetry, and monitoring of spontaneous EEG and evoked responses. Emerging techniques include near infrared optical spectroscopy and brain tissue oximetry for assessment of cerebral oxygenation state, and the EEG bispectral index for assessment of depth of anaesthesia. The use of multimodality monitoring can provide cross validation and improve artifact rejection, but all bedside monitoring techniques that are currently used provide only global measures of CNS physiology. Assessment of regional physiology and metabolism requires the use of modern functional imaging techniques that are beginning to find application in anaesthesia and critical care.

Neonatal intensive care: an obvious, yet difficult area for cerebral near-infrared spectroscopy

The first clinical application of near-infrared spectroscopy (NIRS) 11 years ago was on the head of newborn infants under intensive care. Since then much credible and some important data have been accumulated in this area of research. The best data have been obtained using manipulation of arterial oxygen saturation to obtain single or repeated estimates of cerebral blood flow or cerebral blood volume, or interference with cerebral venous return to obtain measures of venous oxygen saturation. It has been more difficult to take advantage of the continuous and noninvasive nature of NIRS. In particular, the value of the cytochrome signal can still be doubted. A role has not yet developed for NIRS in clinical neonatology.

Estimation of Cerebral Blood Flow at Bedside by Continuous Jugular Thermodilution

The Kety-Schmidt technique can be regarded as the reference method for the measurement of cerebral blood flow (CBF). However, the method is somewhat cumbersome for routine use in the intensive care unit (ICU) at the beside. The continuous thermodilution technique developed many years ago for the measurement of coronary sinus blood flow can be applied for the measurement of jugular blood flow (JBF). However, the measurement of JBF by thermodilution has never been validated using the Kety-Schmidt reference method. We first validate the continuous thermodilution in vitro by comparison with a volumetric flow. The thermodilution method is accurate for flows between 50 and 900 ml min-1 with a mean difference volumetric-thermodilution flow of -1 +/- 18 ml min-1 (mean +/- SD), and precise with a coefficient of variability ranging between 1.21% and 2.50%. In vivo accuracy was assessed by comparing in 15 comatose patients CBF measured using the Kety-Schmidt (CBFKS) method and estimated from JBF measured by thermodilution (CBFTH) at four levels of arterial PaCO2 (25, 30, 35, and 40 mm Hg). The mean difference CBFKS-CBFTH is -0.9 +/- 3.6 ml min-1 100 g-1. In vivo precision of the method was good, with a coefficient of variability of 4.1% in mean. We conclude that jugular continuous thermodilution technique is a reliable method for estimating CBF at the bedside. This technique allows repeated measurements jugular bulb blood sampling for brain metabolic studies.

Cerebral blood flow measured with intracerebral laser-Dopplerflow probes and radioactive microspheres

We have measured cerebral blood flow with intracerebral laser-Doppler microprobes in pentobarbital-anesthetized pigs. We compared the results with measurements from laser-Doppler probes placed on the surface of the brain and with blood flow estimation by the radioactive microsphere method. The cerebral blood flow was varied by alterations in inspired carbon dioxide, hemorrhagic hypotension, and high cerebrospinal fluid pressure. The intracerebral probes and the surface probes showed parallel responses to variations in cerebral blood flow. The correlation was closest between surface probes and the intracerebral probes measuring from the cerebral cortex (r = 0.46; P < 0.005). The r value between laser-Doppler flowmetry and radioactive microspheres was 0.41 (P < 0.0005) for all measurements. The correlation to microspheres was best for the probes located 3 or 10 mm into the brain and poorest for the surface probe. In conclusion, intracerebral laser-Doppler flow measurements reflect changes in blood flow, and the technique appears useful for continuous estimates of cerebral blood flow.

Middle cerebral artery blood flow velocity studied during quiet breathing, reflex hypercapnic breathing and volitionally copied eucapnic breathing in man. Voluntary control of breathing.

The cerebrovascular circulation can be assessed non-invasively in man using transcranial doppler (TCD) velocimetry (1). The change in flow velocity pulse wave is proportional to the change in blood flow in that vessel, assuming cross sectional area of the artery studied to be constant. Such changes have been shown to correlate well with changes in cerebral perfusion in response to hypercapnia (3). TCD estimates of cerebral blood flow is increased when subjects performed both physical and cognitive activities (6) or when they were presented with visual stimuli (2). This suggests that TCD is capable of detecting changes in cerebral blood flow which accompany cerebral activity. In this study we have tested the hypothesis that volitionally controlled breathing is accompanied by an increase in middle cerebral artery (MCA) blood flow velocity (bfv) independent of changes in PCO2.

CEREBRAL BLOOD FLOW MEASURED BY NEAR INFRARED SPECTROSCOPY (NIRS) IN CHILDREN UNDERGOING OPEN HEART SURGERY

A new non-invasive method for repeated estimation of cerebral blood flow (CBF) in infants and children durning non-ppulsatile cardiopulmonary bypass (CPB) is described. The method is derived from the Fick principle, using oxyhaemoglobin (HbO2) as a non-diffusible tracer. A sudden change in O2 flow in to the oxygenator causes a change in arterial saturation (SaO2) which is measured by an optical oximeter, and in cerebral [HbO2], which is detected by NIRS: CBF is calculated from the expression: where k is a constant reflecting the molecular weight of haemoglobin and tissue density.[11] is the arterial haemoglobin concentration. CBF was measured on 16 occasions in 6 children undergoing CPB, median age 5.3 (range 4-62) months. Near-infrared light was transmitted from and returned to the spectrometer by fibre optic cables applied to the head. After a stable baseline of 88-%% SaO2 (median 94%) had been achieved for at least 10 seconds, a rise in SaO2 of 2-10% (median 5%) was induced. Values for CBF of 9-54 ml.100g−1.min were obtained. Preliminary data from two children showed that at full pump How median CBF was 47 (range 41-54) ml 100g−1.min−1 and at half flow was 2.1 (range 22-29) ml.100g−1.min−1. The method warrants further study but suggests that routine, repealed and non-invasive measurements of CBF during CPB may now be possible.

Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebral arteries in healthy adults.

To noninvasively estimate cerebral blood flow volume, a prospective study of color duplex sonography of the common, external, and internal carotid arteries and vertebral arteries of healthy adults was done. Cerebral blood flow was calculated with the sum of flow volumes in the internal carotid and vertebral arteries of both sides. Using a 7.0-MHz linear transducer of a computed sonography system, cervical arteries of 48 volunteers (23 women, 25 men; mean age, 35 +/- 12 years) were examined. We measured angle-corrected time-averaged velocities and the diameter of the vessels and calculated the flow volumes of all arteries. In addition, peak systolic, maximum end-diastolic, and time-averaged maximum velocities and the resistance, pulsatility, and spectral broadening indexes were determined. Furthermore, we analyzed the side-to-side difference, age dependence, and long-term reproducibility of these parameters. The mean +/- SD values of flow volumes in the common, internal, and external carotid and vertebral arteries were 470 +/- 120, 265 +/- 62, 160 +/- 66, and 85 +/- 33 mL/min on either side, respectively. Total cerebral blood flow was 701 +/- 104 mL/min (corresponding to 54 +/- 8 mL/100 g per minute), with no variation in age or sex. Long-term reproducibility of cerebral blood flow and flow volumes in all vessels was significant (P < .01). We conclude that color duplex sonography of cervical arteries is potentially a practical method for estimating total cerebral blood flow. This noninvasive technique may be ideally suited for bedside and follow-up examinations of the critically ill patient. In future studies it should be compared with established radionuclide techniques.

Regional cerebral blood flow estimation by neural network-based parametric regression analysis

An artificial neural network (ANN) model was proposed for real-time estimation of regional cerebral blood flow (rCBF), by given head and expired air curves obtained through 133Xe inhalation. The network was constructed according to a regression model described by a linear differential equation. Experimental results compare well with those obtained by conventional curve fitting strategies, but the parameter estimation process is much simplified. A systematic procedure in developing ANN for parametric regression analysis was introduced; networks are constructed according to the selected regression model so that the obtained weights of a trained network directly represent parameters of the regression model which best fits the observed data set. Such a design-oriented methodology extends the classification-based applications of ANN to parametric regression analysis, and therefore may have more generalized applications besides rCBF estimation.

Alterations in regional cerebral blood flow, with increased temporal interhemispheric asymmetries, in the normal elderly

Single photon emission computed tomography (SPECT) with the tracer 99Tcm-hexamethylpropyleneamine oxime (HMPAO) provides images allowing semiquantitative estimation of regional cerebral blood flow (rCBF). Despite its widespread use there is little data on patterns of rCBF obtained using this tracer in normal elderly subjects, although other methods of measurement suggest a fall in cerebral blood flow with age. Furthermore, the detection of interhemispheric asymmetries on HMPAO SPECT is often used to identify areas of pathological abnormality yet there is little data on the prevalence of asymmetries in the normal elderly. An increased prevalence of asymmetries in the elderly may explain the difficulties recently reported in using functional imaging in the diagnosis of Alzheimer's dementia. Patterns of HMPAO uptake were compared in 10 young (mean age 24.9 years; range 21-34 years) and 10 elderly (mean age 74.1 years; range 70-76 years) normal subjects. Percentage interhemispheric asymmetry ratios were calculated and found to be greater in the elderly, particularly for the temporal cortex (young 0.87%, elderly 3.73%, P < 0.001). The proportion of injected HMPAO taken up by the head was 29% higher in the younger age group. Analysis of regional uptake revealed that this trend towards reduced uptake in the elderly was a global phenomenon affecting all brain regions. The increased interhemispheric asymmetries seen in the elderly imply that a higher threshold for interpreting asymmetries as abnormal must be used in the elderly, particularly for the temporal cortex.

A study on statistically reliable and computationally efficient algorithms for generating local cerebral blood flow parametric images with positron emission tomography

With the advent of positron emission tomography (PET), a variety of techniques have been developed to measure local cerebral blood flow (LCBF) noninvasively in humans. A potential class of techniques, which includes linear least squares (LS), linear weighted least squares (WLS), linear generalized least squares (GLS), and linear generalized weighted least squares (GWLS), is proposed. The statistical characteristics of these methods are examined by computer simulation. The authors present a comparison of these four methods with two other rapid estimation techniques developed by Huang et al. (1982) and Alpert (1984), and two classical methods, the unweighted and weighted nonlinear least squares regression. The results show that these methods can take full advantage of the contribution from the fine temporal sampling data of modern tomographs, and thus provide statistically reliable estimates that are comparable to those obtained from nonlinear LS regression. These methods also have high computational efficiency, and the parameters can be estimated directly from operational equations in one single step. Therefore, they can potentially be used in image-wide estimation of local cerebral blood flow and distribution volume with PET.

Comparison of PET measurements of cerebral blood flow and glucose metabolism for the localization of human epileptic foci

We compared the relative sensitivity of two interictai PET techniques, bolus injection of [ 15O] labeled water for estimation of cerebral blood flow (H 2 15O CBF-PET), and 18F 2-deoxyglucose ( 18FDG-PET) for cerebral glucose metabolism (CMRglc), and T2-weighted magnetic resonance imaging, in 28 patients with medically intractable complex partial seizures undergoing evaluation for surgery. There were statistically significant associations between lateralization by 18FDG-PET, and MRI, but not H 2 15O CBF-PET, and lateralization of the epileptic focus as defined by scalp-sphenoidal ictal EEG. Fifteen patients had surgery or subdural electrodes. 18FDG-PET was more closely associated with a good outcome than H 2 15O CBF-PET, which, in addition, showed hypoperfusion contralateral to the epileptic temporal lobe in several cases. H 2 15O sensitivity may have been reduced by technical factors, but 18FDG-PET appears to be more specific for localization of epileptic zones.

Effect of Stable Xenon Inhalation on Internal Carotid Artery Blood Flow in Unanesthetized Monkeys

Stable xenon (Xe) gas, at inspired concentrations above 30%, reportedly increased cerebral blood flow (CBF) in animals and humans. An unpredictable Xe-induced elevation of CBF could result in erroneous CBF values being measured by Xe-enhanced computed tomography (Xe-CT). In order to detect a potentially rapid and transient effect of Xe on CBF, estimations of supratentorial CBF were obtained by Doppler flow probes chronically and bilaterally implanted on the internal carotid arteries of five adult monkeys. The unanesthetized monkeys with a clear plastic helmet were equilibrated for 15 min on a control gas (33% N2/67% O2) randomly exposed for 5 min to gas mixtures of either 33% Xe/67% O2 or 10% CO2/23% N2/67% O2. The mean control bilateral internal carotid artery blood flow (ICABF) was 23 +/- 10 ml/min (mean +/- SD), mean arterial pressure (MAP) was 101 +/- 13 mm Hg, and PaCO2 was 34 +/- 6 mm Hg. Inhalation of 33% Xe in O2 did not change the ICABF, MAP, or PaCO2. Inhalation of 10% CO2 in O2 increased the ICABF to 39 +/- 15 ml/min (p <0.001), MAP to 112 +/- 16 mm Hg (p <0.05), and PaCO2 to 54 +/- 5 mm Hg (p <0.001). The lack of change in ICABF and PaCO2 with 32% Xe inhalation suggests that a clinically relevant change in CBF is unlikely.

In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption

To explore the feasibility of in vivo 17O NMR for the estimation of cerebral blood flow and oxygen consumption, in vivo 17O NMR spectroscopy and imaging were employed in animal models. In the spectroscopy, the changes in the 17O NMR signal intensity after the injection of H 2 17O and the inhalation of 17O 2 gas were obtained every 4 seconds with sufficient signal-to-noise ratios for the quantification of cerebral blood flow and oxygen consumption. In the imaging, although the time and spatial resolutions were insufficient for the quantification of H 2 17O, 17O NMR images of rabbit brain could be obtained, indicating that it is possible to map cerebral blood flow and oxygen consumption by 17O NMR imaging.