Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI.

Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.     

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.     

Acute effects of smoking on human cerebral blood flow: a transcranial Doppler ultrasonography study.

Middle cerebral artery (MCA) flow velocity was continuously monitored during smoking in an observational study (n = 14) using transcranial Doppler (TCD) ultrasonography. Cerebral autoregulatory vasodilator capacitance under inspired CO2 challenge was also measured before smoking and at peak smoking effect. Several puffs on a single lighted cigarette over a period of five minutes acutely increased MCA mean flow velocity in every subject (group mean increase: 19%, individual increases ranged 2-64%) with a response onset and offset detectable within several seconds of beginning and ending smoking. The mechanism for the increase in MCA flow velocities appeared to be independent of the CO2 autoregulatory mechanism. Gender subgroup analysis showed smoking acutely suppressed the CO2 vasodilator capacitance by 56% in men but only by 5% in women (p = 0.05). The magnitude of the acute smoking-induced increases in MCA flow velocities appeared to be independent of the estimated cigarette yields for nicotine, carbon monoxide, and "tar." Smoking in healthy subjects acutely increased MCA mean flow velocity, which may reflect a global increase in cerebral blood flow via complex influences on the cerebral autoregulation.     

Regional cerebral blood flow in children--normal value and regional distribution of cerebral blood flow in childhood

The changes in CBF and rCBF through the entire age range include the rapid period in childhood was reported. Sixteen children between the ages of 1 and 15 and 14 adults were studied. These 30 subjects were either volunteers of out-patients without CT and EEG abnormalities. rCBF was measured by the 133Xe intravenous injection method using Varmet rCBF analyzer. Ther relationship between age and CBF, the correlation coefficient was calculated based on the regression equations and the regression curve with the highest correlation was chosen. For the analysis of rCBF, he mean rCBF values (ISI) of 3 channels corresponding to the frontal, temporal, parietal and occipital lobes were expressed as a percentage of the hemispheric CBF. The hemispheric blood flow (ISI and CBF gray) of children less than 5 years of age was approximately twice that found in adults. This value decreased rapidly with age and in the 10-15 years the blood flow was approximately 1.3-fold that of adults. Thereafter, there was a slow decrease and a negative correlation with age was found. The decrease showed the correlation on the following equations; y = 146.5 - 58.5 log x. (r = -0.903) for ISI and log y = 2.26 - 0.29 log x. (r = -0.881) for CBF gray, which was statistically significant. In contrast, the CBF white showed a slightly higher value in the 1-2 years old children, but thereafter the CBF did not show a notable decreases with age. Through the entire age range, a best fit for the Fw values was found with : y = 18.3 + 37.5/x. (r = 0.798), which was also statistically significant.     

Intraoperative monitoring of cerebral blood flow during ventricular shunting in hydrocephalic pediatric patients

Several studies have demonstrated lowered cerebral blood flow (CBF) in patients with hydrocephalus and symptoms of raised intracranial pressure. Ventricular shunting in such cases permits a sudden increase in CBF. The pathophysiology of functional brain deficit secondary to hydrocephalus is little understood. Improvement of the patient's clinical status after drainage of CSF suggests that cerebral dysfunction is not necessarily due to permanent brain damage. In fact, it improves rapidly after ventricular taps. In view of this it would be helpful to monitor cerebral perfusion. The transcranial Doppler (TCD) ultrasonography technique allows real-time monitoring of the intracranial circulation and makes it possible to evaluate the physiopathological correlation between ventricular dilatation and CBF. Continuous monitoring of the middle cerebral artery (MCA) by TCD was performed in three hydrocephalic children (2 months, 14 months, and 8 years old) during a ventricular-peritoneal shunt operative procedure. A TC-2000S device provided by an IMP-F fixed probe was utilized. In all patients, when the lateral ventricle was shunted and the CSF could flow away, a clear and sudden increase of flow velocity above 30% was detected. The pulsatility index (PI) was also pathologically increased in all patients. A gradual normalization of this index was revealed after the shunting procedure. Our experience has to be considered preliminary, but nonetheless, it suggests a clear correlation between hydrocephalic disease and concomitant CBF alterations. A more consistent number of monitoring performances by TCD during operative procedures will improve our understanding of the role of CBF in the development of functional deficits in hydrocephalic disease.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

Cerebral blood flow response to functional activation

Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue''s increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation.     

Influence of the endothelial glycocalyx on cerebral blood flow in mice.

The endothelial surface layer (glycocalyx) of cerebral capillaries may increase resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline), which cleaves proteoglycan junctions of the glycocalyx. Morphology was investigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser-Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 minutes after heparinase or saline treatment using the iodo[14C]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (PCO2: 120 mm Hg). After heparinase, morphology showed a reduced thickness of the glycocalyx in cortical microvessels by 43% (P < 0.05) compared with saline-treated controls. Under normocapnic conditions, a 15% (P < 0.05) transient increase of cerebral flow velocity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flow and CBF returned to control values ten minutes after the injection. However, during severe hypercapnia, heparinase treatment resulted in a persisting increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). These observations indicate the existence of a flow resistance in cerebral capillaries exerted by the glycocalyx. The transient nature of the CBF increase during normocapnia may be explained by a vascular compensation that is exhausted during severe hypercapnia.     

Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the ability of transcranial Doppler ultrasonography to detect selective circulatory changes during cognitive activity. METHODS: We measured cerebral artery flow velocity in 21 normal volunteers by transcranial Doppler ultrasonography during rest followed by cerebral activation. Mean and peak systolic flow velocities of the anterior, middle, and posterior cerebral arteries were measured during the performance of a commercial video game. We also measured flow velocity of the anterior cerebral arteries in 18 subjects during a mental arithmetic task. Serial measurements of the right and left sides were made with a headband with two probes. RESULTS: We observed a global increase in the flow velocity above baseline measurements during task performance. During the video game, both middle cerebral arteries (t = 2.6, p = 0.02 for the left; t = 3.3, p = 0.004 for the right) and the left posterior cerebral artery (t = 2.2, p = 0.004) had selective increase in mean flow velocity compared with the ipsilateral anterior cerebral artery. This selective activation was most prominent in the right middle cerebral artery, which had a greater degree of activation than the right posterior cerebral artery (t = 2.8, p = 0.013). We did not observe a statistically significant difference between the right and left middle cerebral arteries, but there was a trend toward a greater activation on the right for both the mean velocity (t = 1.7, p = 0.098) and the peak velocity (t = 1.9, p = 0.079). CONCLUSIONS: Our preliminary investigation suggests that this noninvasive technique has the potential to correlate selective cerebral artery flow dynamics with cognitive activity.     

Decreases in regional cerebral blood flow with normal aging

Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.     

Threshold of regional cerebral blood flow for infarction in patients with acute cerebral ischemia

Threshold of regional cerebral blood flow (rCBF) for cerebral tissue survival in relation to time was studied in patients with acute cerebral ischemia with xenon-enhanced computed tomography (XeCT). Case 1: A 58-year-old man with right hemiparesis, total aphasia and a high intensity area of 1 cm 2 in the left insula on diffusion weighted image underwent XeCT CBF study before and after intra-arterial local thrombolytic therapy (IALT) on the occluded middle cerebral artery (MCA) 4 hours and 7 hours after stroke onset, respectively. Case 2: A 65-year-old woman with recurrent transient ischemic attacks (TIAs) caused by severe stenosis of the left MCA underwent XeCT CBF study 5 hours after onset of the last attack. XeCT was conducted by 5-min wash-in method. In Case 1 the rCBF in the pre-IALT MCA territory was 4 to 19 ml/100 g/min. The area where rCBF in the post-IALT increased to above 15 ml/100g/min were saved, but the other area where it remained in the 9 to 14 ml/100 g/min evolved into infarct on subsequent CT scan/MR (magnetic resonance) imaging. The patient was discharged with only mild motor dysphasia. In Case 2 the left corona radiata showed rCBF of 7 ml/100 g/min and this area evolved into infarct on MR imaging. The patient was discharged home with right hemiparesis. Our results showed validity of the rCBF threshold in acute cerebral ischemia reported by Jones et al. Residual rCBF in the acute stage of cerebral ischemic stroke can predict the fate of the lesion.     

Opioid addiction changes cerebral blood flow symmetry

Changes in regional cerebral blood flow (rCBF) due to long-term abuse of opioids such as heroin or morphine are not yet fully understood in humans. The goal of the present study was to investigate rCBF alterations in a large sample of long-term opioid addicts in comparison to healthy controls. We investigated 21 opioid-dependent subjects, who were currently abusing heroin or were enrolled in a methadone or morphine maintenance program, and 36 healthy controls with (99m)Tc-HMPAO single photon emission computed tomography. We found a decrease in rCBF in most regions of interest in patients in comparison to controls. Long-term opioid dependence seems to decrease prefrontal CBF in particular. A right-greater-than-left CBF asymmetry in healthy subjects was reversed in patients. This change in CBF symmetry could reflect the different emotional status of opioid-dependent patients. Our findings are in line with neuropsychological investigations indicating a correlation of mood states with lateralization of hemispheric activation patterns.     

Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats

The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.     

Regional cerebral blood flow in stroke: hemispheric effects of cognitive activity

Regional cerebral blood flow (rCBF) was measured with the xenon-133 inhalation technique in 15 patients with unilateral cerebral infarction and 12 matched controls. Measurements were performed during a standard resting baseline condition and during the performance of standardized verbal analogies and spatial line orientation tasks. Resting and activated CBF were lower in patients than in controls, and there were differences in the hemispheric pattern of activated CBF. Control subjects replicated earlier findings of asymmetric increase in CBF for the cognitive tasks, whereas patients showed abnormalities in lateralized CBF changes consistent with side of infarction. These findings underscore the utility of cognitive challenges in the study of rCBF in stroke. This can lead to an experimental paradigm in clinical studies of the relation between behavioral deficits and regional brain dysfunction and may also improve the utility of CBF measurements in clinical settings.     

Regional cerebral blood flow in long-term heavy cannabis use

Regional cerebral blood flow (rCBF) was measured by the 133Xenon inhalation method in nine male chronic cannabis users. The rCBF level in cannabis users was significantly (11%) lower than that of age- and sex-matched healthy controls. Four of the subjects were reexamined after 9-60 days of detoxification and showed a significant (12%) increase of the CBF level at followup. No significant regional flow abnormalities were noted. The global CBF reduction seen in the early phase of detoxification is most likely the consequence of the dysfunction of the central nervous system accompanying chronic cannabis use.     

Convergent evoked potential and cerebral blood flow evidence of task-specific hemispheric differences

Two independent measures of cerebral activation, probe evoked potentials (EPs) and regional cerebral blood flow (rCBF) were used to assess the relative contribution of the left and right parietal areas during a task requiring mental rotation of geometric figures. The objective of the study was to ascertain the degree of concordance in these two measures in revealing task-specific hemispheric activation. Since rCBF is a direct measure of regional metabolic rate and has been shown to reflect expected task-specific hemispheric asymmetries, its concordance with probe EP data could serve to validate the assumptions underlying interpretation of the latter. EPs to strobe flashes and rCBF were simultaneously measured in 19 dextral normal adults during a mental rotation task and during a control task involving similar stimulation and response requirements. A high degree of concordance in these two measures was obtained, with both revealing significantly greater activation of the right parietal region during the mental rotation task. Besides supporting the notion of predominant right hemisphere involvement in this type of visuo-spatial operation, this study suggests that either measure may be used as a reliable index of task-specific regional cerebral asymmetries.     

Dynamic imaging of cerebral blood flow using laser speckle.

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology.     

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.     

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.     

Different mental imagery abilities result in different regional cerebral blood flow activation patterns during cognitive tasks.

Using regional cerebral blood flow (rCBF) imaging, two populations having high and low imagery abilities were compared at rest and while performing two cognitive tasks: silent verb conjugation and mental imagery. The imagery task produced an rCBF increase in the left visual association and left frontal cortices in both groups. Differences between high and low imagers were observed on global and regional flow responses to cognitive tasks: low imagers showed a whole cortex CBF increase during both tasks; high imagers showed a right dominance in the visual association cortex in all conditions, and in the parietal association cortex at rest.     

Blood velocity in the middle cerebral artery and regional cerebral blood flow during carotid endarterectomy

Blood flow velocity in the middle cerebral artery, determined by transcranial Doppler ultrasonography, was monitored during 31 carotid endarterectomies. Electroencephalogram (EEG) was also monitored, and regional cerebral blood flow (rCBF) was measured. The relation between rCBF and mean velocity was dependent on the rCBF level; the correlation was strong if rCBF was less than 20 ml/100 g/min but weak if rCBF was greater than that level. Ipsilateral EEG suppression was related to a rCBF threshold of 9 ml/100 g/min and to a mean velocity threshold of 15 cm/sec; the rCBF threshold was more specific for EEG change. Postischemic hyperemia was evident in measurements of mean velocity but not of rCBF. These disparities between mean velocity and rCBF seemed to be due to three factors: 1) disproportionately high mean velocity in patients with stenosis of the middle cerebral artery, 2) a nonlinear relation between mean velocity and rCBF, and 3) the anatomically different regions of the brain in which mean velocity and rCBF are measured. The velocity measurement appeared to be relatively more sensitive than rCBF to hemodynamic events in the corpus striatum and internal capsule.