Uncoupling Of Cerebral Blood Flow Research Articles

Uncoupling of cerebral blood flow and brain oxygen saturation under non-pulsatile flow conditions

Introduction Non-pulsatile blood flow has been associated with altered microcirculatory perfusion. Soon after loss of pulsatility a marked heterogenous flow profile in the very small vessels ensues that is coupled with impaired oxygen extraction [1]. We investigated if changes in cerebral blood flow during non-pulsatile perfusion would affect brain tissue oxygenation assessed by near-infrared spectroscopy. Methods After approval by the local ethics committee thirty-two patients were included in this trial. They were studied during general anaesthesia, and stable hemodynamic conditions. Cerebral blood flow velocity in the middle cerebral artery was measured during non-pulsatile flow in the course of cardiac surgery on total extracorporeal bypass and again postoperatively on the intensive care unit during pulsatile flow. We modified cerebral blood flow by changing arterial partial pressures of carbon dioxide between 30, 40 and 50 mmHg. This was conducted either by a change of sweep gas flow at the heart lung machine or by changing respiratory rate at the respirator. In addition to flow measurements patients' regional brain oxygenation was determined. Relative changes in blood flow velocity were plotted against relative changes in regional brain saturation for both flow conditions and compared using Pearson's correlation. A p-value Results Absolute cerebral blood flow velocity was slightly higher during non-pulsatile flow when serum hemoglobin was diluted. Relative changes in cerebral blood flow velocity and regional brain oxygenation were tightly coupled independent of the flow condition. R-values for non-pulsatile and pulsatile blood flow were 0.724 and 0.796, respectively. However, during non-pulsatile flow the slope of the regression line was less steep as compared with pulsatile flow (P Discussion Despite greater cerebral perfusion during hypercapnia and non-pulsatile flow there was no equivalent rise in cerebral oxygenation. Assuming similar cerebral oxygen delivery this finding could be explained by impaired brain oxygen extraction in the high flow range while partial pressure of carbon dioxide was elevated. In contrast, during hypocapnia, when cerebral blood flow was decreased to a greater extent as during pulsatile flow, the concomitant desaturation was less pronounced. Both findings are in line with shunting on the microcirculatory level, whereby hyperperfused vessels coexist with vessels lacking adequate flow. These findings substantiate that loss of pulsatility seems to negatively affect nutritive tissue perfusion. Raised neurological morbidity in patients supported with non-pulsatile extracorporeal cardiac assist devices could potentially be attributable to the observed perfusion deficit [2].

UBC-Nepal Expedition: Cerebrovascular Responses to Exercise in Sherpa Children Residing at High Altitude.

Understanding the process of successful adaptation to high altitude provides valuable insight into the pathogenesis of conditions associated with impaired oxygen uptake and utilization. Prepubertal children residing at low altitude show a reduced cerebrovascular response to exercise in comparison to adults, and a transient uncoupling of cerebral blood flow to changes in the partial pressure of end-tidal CO2 (PETCO2); however, little is known about the cerebrovascular response to exercise in high-altitude native children. We sought to compare the cerebral hemodynamic response to acute exercise between prepubertal children residing at high and low altitude. Prepubertal children (n = 32; 17 female) of Sherpa descent (Sherpa children [SC]) at high altitude (3800 m, Nepal) and maturational-matched (n = 32; 20 female) children (lowland children [LLC]) residing at low altitude (342 m, Canada). Ventilation, peripheral oxygen saturation (SpO2), PETCO2, and blood velocity in the middle and posterior cerebral arteries (MCAv and PCAv) were continuously measured during a graded cycling exercise test to exhaustion. At baseline (BL), PETCO2 (-19 ± 4 mmHg, p < 0.001), SpO2 (-6.0% ± 2.1%, p < 0.001), MCAv (-12% ± 5%, p = 0.02), and PCAv (-12% ± 6%, p = 0.04) were lower in SC when compared with LLC. Despite this, the relative change in MCAv and PCAv during exercise was similar between the two groups (p = 0.99). Linear regression analysis demonstrated a positive relationship between changes in PETCO2 with MCAv in SC (R2 = 0.13, p > 0.001), but not in LLC (R2 = 0.03, p = 0.10). Our findings demonstrate a similar increase in intra-cranial perfusion during exercise in prepubertal SC, despite differential BL values and changes in PETCO2 and SpO2.

TPA variant tPA-A296-299 Prevents impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1.

Tissue-type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole FDA-approved drug for treatment of ischemic stroke. Upregulation of c-Jun-terminal kinase (JNK) after stroke contributes to tPA-mediated impairment of autoregulation, but the role of endothelin-1 (ET-1) is unknown. Based on the Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after TBI, but correlation with hippocampal histopathology after stroke has not been established. We propose that given after stroke, tPA activates N-Methyl-D-Aspartate receptors (NMDA-Rs) and upregulates ET-1 in a JNK dependent manner, imparing autoregulation and leading to histopathology. After stroke, CBF was reduced in the hippocampus and reduced further during hypotension, which did not occur in hypotensive sham pigs, indicating impairment of autoregulation. Autoregulation and necrosis of hippocampal CA1 and CA3 neurons were further impaired by tPA, but were preserved by the ET-1 antagonist BQ 123 and tPA-A,296-299 a variant that is fibrinolytic but does not bind to NMDA-Rs. Expression of ET-1 was increased by stroke and potentiated by tPA but returned to sham levels by tPA-A296-299 and the JNK antagonist SP600125. Results show that JNK releases ET-1 after stroke. Tissue-type plasminogen activator -A296-299 prevents impairment of cerebral autoregulation and histopathology after stroke by inhibiting upregulation of ET-1.

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

Noninvasive evaluation of the correlation between regional cerebral blood flow and intraventricular brain temperature in temporal lobe epilepsy

IntroductionIn temporal lobe epilepsy (TLE), an uncoupling of cerebral blood flow (CBF) and metabolism is indicated. The aim of this study was to clarify this relationship by investigating intraventricular brain temperature (BT) and CBF in TLE using a noninvasive MRI technique. Material and methodsWe recruited 38 subjects with left TLE and 39 subjects with right TLE. All patients underwent an MRI examination including diffusion-weighted imaging (DWI) and pseudo-continuous arterial spin labeling (pCASL). Intraventricular BT was calculated by a DWI thermometric technique, and regional CBF was obtained from pCASL images, and we analyzed the relationship between them using the statistical parametric mapping 8 software (SPM8). ResultsIn only the left TLE group, there was a significant negative correlation between CBF and BT in the left inferior frontal gyrus. Positive correlations in the bilateral posterior poles were also found at the trend level in left TLE group. The patients with right TLE showed no significant correlation. ConclusionOur results may reflect a regional uncoupling of blood flow and metabolism in those brain areas, and they may indicate that TLE has different metabolic regulation systems in the brain.

Cerebral hemodynamics: concepts of clinical importance

Cerebral hemodynamics and metabolism are frequently impaired in a wide range of neurological diseases, including traumatic brain injury and stroke, with several pathophysiological mechanisms of injury. The resultant uncoupling of cerebral blood flow and metabolism can trigger secondary brain lesions, particularly in early phases, consequently worsening the patient's outcome. Cerebral blood flow regulation is influenced by blood gas content, blood viscosity, body temperature, cardiac output, altitude, cerebrovascular autoregulation, and neurovascular coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and adenosine. A better understanding of these factors is valuable for the management of neurocritical care patients. The assessment of both cerebral hemodynamics and metabolism in the acute phase of neurocritical care conditions may contribute to a more effective planning of therapeutic strategies for reducing secondary brain lesions. In this review, the authors have discussed concepts of cerebral hemodynamics, considering aspects of clinical importance.

TCD Diastolic Velocity Decay and Pulsatility Index Increment in PVS Cases

Functional neuroimaging has provided new insights for assessing cerebral function in persistent vegetative state patients (PVS). Compared to controls, positron emission tomography and single photon emission tomography have shown a substantial reduction of global brain cerebral glucose metabolism and perfusion in PVS. Doppler ultrasonography (TCD) assesses local blood flow velocity and direction in the proximal portions of large intracranial arteries; it is a noninvasive technique, and it can be carried out at the bedside. To date, few studies have applied TCD to study PVS. We assessed intracranial circulation by TCD in five PVS patients. The cause of brain insult was hypoxic encephalopathy in four cases, and the other suffered an embolic cerebral infarct causing a top of the basilar artery syndrome. The sample volume was set at 12 mm; power output and gain settings were maximized as needed. The temporal bone acoustic window was not suitable for intracranial vessel insonation in all patients. As an alternative, the internal carotid artery siphon was assessed by orbital insonation between 55-70 mm. Systolic velocity was within a normal range, between 44 and 62 cm/second in all cases. However, the diastolic amplitude was reduced, as well as the end diastolic velocity, and the pulsatility index was increased in all patients. We conclude that TCD diastolic velocity decrement and PI augmentation in our cases might be related to uncoupling of cerebral blood flow and cerebral metabolic rate, arising from reduced cerebral glucose consumption and oxygen uptake, after extensive brain injury.

Hemodynamic Changes after Visual Stimulation and Breath Holding Provide Evidence for an Uncoupling of Cerebral Blood Flow and Volume from Oxygen Metabolism

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-dependent (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO(2)). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, visual stimulation (14 secs flashing checkerboard) and breath-hold (4 secs exhale+14 secs breath hold) experiments were performed in alternating sequence on healthy volunteers using BOLD, CBV-weighted, and CBF-weighted fMRI. After visual stimulation, the BOLD signal persisted for 33+/-5 secs (n=9) and was biphasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20+/-5 and 20+/-3 secs, respectively. After breath hold, the BOLD signal returned to baseline (23+/-7 secs) at the same time (P>0.05) as CBV (21+/-6 secs) and CBF (18+/-3 secs), without a poststimulus undershoot. These data suggest that the BOLD undershoot after visual activation reflects a persistent increase in CMRO(2). These observations support the view that CBV and CBF responses elicited by neuronal activation are not necessarily coupled to local tissue metabolism.

Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated BOLD fMRI study

Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO 2). In this study, we implemented a quantitative R 2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO 2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+ 46.6%, ± 11.3, mean and standard error), visual stimulation increased both CBF (+ 47.9%, ± 2.9) and CMRO 2 (+ 20.7%, ± 1.4), and caffeine decreased CBF (− 34.5%, ± 2.6) with a non-significant change in CMRO 2 (+ 5.2%, ± 6.4). The coupling between CBF and CMRO 2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R 2∗ is a promising approach for evaluating CBF and CMRO 2 changes in response to pharmacological interventions.

Uncoupling of cerebral blood flow and metabolism after cerebral contusion in the rat.

Positron emission tomography scans of patients with head injuries often show discrete areas of increased 18F-fluorodeoxyglucose uptake ("hot spots") when performed hours to days after the initial ictus. Using quantitative autoradiographic methods, the authors have investigated whether cerebral blood flow and glucose metabolism are uncoupled 2 hours after controlled head injury in an animal model, and whether any "hot spots" are accompanied by changes in cerebral glucose concentration. Experiments were performed on 18 anesthetized, ventilated (1.5% halothane in 2:1 nitrous oxide:oxygen) Sprague-Dawley rats weighing 300 to 330 g. A burr hole was made over the left parietal cortex, and all animals received a piston impact on the intact dura (2 mm in diameter, 2.0 m/sec, 2 mm in depth). All animals remained anesthetized and ventilated for a further 2 hours, after which quantitative autoradiography was used to determine either (1) local cerebral blood flow (LCBF) using 14C-iodoantipyrine, (2) local cerebral glucose utilization (LCGU) using 14C-deoxyglucose, or (3) local cerebral glucose content (LCGC) using 14C-methylglucose. Local CBF, LCGU, and LCGC were measured in five regions adjacent to the contusion, and values then were normalized on the contralateral cortex. Normalized LCBF, LCGU, or LCGC varied in parallel in ipsilateral cortex (no change) and in the ischemic core of the contusion (reduced). However, there were marked changes in the patterns observed in the boundary zone (within 1 mm of the contusion). In all six rats used for LCGU measurement, there were discrete areas of high metabolism, whereas in all six rats used for LCBF measurement, flow was universally depressed in the boundary zone. Of the six rats used for LCGC determination, there was a discrete area of high signal in only one. The authors conclude that there are discrete areas of uncoupling of cerebral blood flow and metabolism after head injury within 2 hours of cerebral contusion in the rat that cannot be explained by changes in cerebral glucose content in the majority of animals.

Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates with acute thromboembolic stroke.

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was > 40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.

Preserving Plasticity: New Directions in Research for the Developing Brain

After completing this article, readers should be able to: 1. Characterize the process of corticogenesis. 2. Describe findings of magnetic resonance imaging of the developing brain. Cerebral development of the fetus is under genetic control, and during the third trimester of gestation, synapse development, dendritic spine elaboration, and cortical-cortical connections proceed as the period of developmental plasticity begins. In contrast to infants born at term, those who are born preterm can suffer significant developmental disability; many reports have shown that the neurodevelopmental outcome of very low-birthweight preterm infants is related directly to gestational age at birth. Infants weighing less than 1,000 g at birth now represent almost 1% of all live births in the United States, and the survival rate for this population approaches 85%. In stark contrast to the improved survival, however, are the emerging reports of neurodevelopmental disability in these very tiny and frequently critically ill infants. The incidence of cerebral palsy is increasing as the survival rate increases, and the incidence of cognitive deficits in this population has not changed during the past decade. The incidence of major neurodevelopmental handicaps in very preterm infants ranges from 12% to 32%, and even “healthy” preterm infants experience a high degree of educational difficulties. When we examined 200 very low-birthweight survivors of the Randomized Indomethacin Intraventricular Hemorrhage Prevention Trial who had reached 8 years of age, more than 50% required special assistance in school or were educated in full-time special education classrooms, and 25% already had repeated at least one grade in school. These data are consistent with those of other observers and indicate that preterm birth disrupts the normal genetically programmed series of events regulating corticogenesis in the developing brain. Intracranial hemorrhage (ICH), or hemorrhage into the germinal matrix tissues of the developing brain, is a major cause of neurodevelopmental handicap …

Uncoupling of cerebral blood flow and glucose utilization in the regenerating facial nucleus after axotomy.

Axotomy is known to activate various metabolic processes including protein synthesis and glucose utilization in the motor nucleus. Although it is generally assumed that the local cerebral blood flow (CBF) fluctuates in response to the axonal reaction, there has been no direct evidence for changes in CBF in the motor nucleus following axotomy. In this study, the CBF in the facial nuclei was measured after axotomy of the facial nerve employing the [14C]iodoantipyrine method to evaluate the relation between the CBF and axonal reaction. Following unilateral facial nerve axotomy in neonates, which induced neuronal degeneration in the facial nucleus, the CBF and glucose uptake was significantly decreased on the operated nucleus, suggesting that CBF and glucose metabolism are coupled in the degenerating nucleus. In contrast, after axotomy in adults, which induced regeneration of neurons and glial reactions, glucose uptake was increased on the operated nucleus, while the CBF did not differ significantly between the operated and unoperated nucleus. These findings imply that glucose metabolism and CBF are uncoupled in the regenerating nucleus, suggesting that the relation between CBF and metabolism in the regenerating nucleus following axotomy may clearly contradict the classical concept of a tight coupling between CBF and metabolism.

Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study.

To determine the extent and duration of change in extracellular glutamate levels after human traumatic brain injury (TBI), 17 severely brain injured adults underwent implantation of a cerebral microdialysis probe and systematic sampling was conducted for 1 to 9 days postinjury. A total of 772 hourly microdialysis samples were obtained in 17 patients (median Glasgow Coma Scale score 5+/-2.5, mean age 39.4+/-20.4 years). The mean (+/-standard deviation) glutamate levels in the dialysate were evaluated for 9 days, during which the mean peak concentration reached 25.4+/-13.7 microM on postinjury Day 3. In each patient transient elevations in glutamate were seen each day. However, these elevations were most commonly seen on Day 3. In all patients there was a mean of 4.5+/-2.5 transient elevations in glutamate lasting a mean duration of 4.4+/-4.9 hours. These increases were seen in conjunction with seizure activity. However, in many seizure-free patients the increase in extracellular glutamate occurred when cerebral perfusion pressure was less than 70 mm Hg (p < 0.001). Given the potential injury-induced uncoupling of cerebral blood flow and metabolism after TBI, these increases in extracellular glutamate may reflect a degree of enhanced cellular crisis, which in severe head injury in humans appears to last up to 9 days. Extracellular neurochemical measurements of excitatory amino acids may provide a marker for secondary insults that can compound human TBI.

Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans.

Uncoupling of cerebral blood flow (CBF) and oxidative metabolism is observed after severe head injury in comatose patients; however, the mechanism(s) involved remain undefined. Adenosine can produce cerebral vasodilation and reduce neuronal activity and is a possible mediator of uncoupling. We hypothesized that cerebrospinal fluid (CSF) adenosine concentrations would be increased during uncoupling of CBF and oxidative metabolism, defined as a narrow arterio-jugular venous oxygen difference [D(a-v)O2 4 vol%] after head injury. Adenosine concentrations were measured using fluorescent-based high-pressure liquid chromatography in 67 CSF samples obtained from 13 comatose (Glasgow Coma Scale score 7) adult patients who sustained a severe closed head injury. At the time each sample was obtained, CBF was measured by the xenon-133 method, and blood samples were obtained for determination of D(a-v)O2. CSF adenosine concentration was negatively associated with D(a-v)O2 (P < 0.05, generalized multivariate linear regression model). In addition, CSF adenosine concentration was increased when D(a-v)O2 was 4 versus > 4 vol% (38.5 [3.2-306.3] versus 14.0 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.025) and in patients who died versus survivors (40.1 [6.9-306.3] versus 12.9 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.001). The association between increased CSF adenosine concentration and a reduction in global cross-brain extraction of oxygen supports a regulatory role for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism severe head injury in humans.

The role of adenosine during the period of delayed cerebral swelling after severe traumatic brain injury in humans.

Cerebrovascular failure with an increase in cerebral blood volume or hyperemia contributes delayed cerebral swelling after severe traumatic brain injury (TBI) in humans. One mediator that could be involved in this process is adenosine, which stimulates a concurrent reduction in cerebral metabolic rate and an increase in cerebral blood flow (CBF). We hypothesized that during the delayed phase after TBI in humans: 1) CSF adenosine concentration is associated with uncoupling of CBF and CMRO2, and 2) adenosine formation is driven by mediator-stimulated cAMP production in injured brain. We serially measured CBF and AVDO2, and CSF adenosine, lactate and cAMP after severe TBI in 13 humans. After 6-18 h, global CBF was increased and AVDO2 was reduced vs all other time periods, defining the uncoupling phase as the period between 18 h and 5 days. CSF adenosine concentration was negatively associated with AVDO2 and strongly associated with death (both p < 0.05), CSF lactate peaked during the initial 18 h, but remained increased for 5 days. CSF cAMP concentration was not increased (vs normal). The association between CSF adenosine concentration and death, and the correlation between uncoupling of CBF and oxidative metabolism and CSF adenosine concentration support our first hypothesis. In contrast, the low levels of cAMP in CSF observed in these patients, but persistently increased CSF lactate, refute our second hypothesis. We speculate that hyperglycolysis or occult ischemic foci are possible sources of ATP breakdown and adenosine formation, and that adenosine is playing a neuroprotective role.

Crossed cerebellar hypoperfusion indicates the degree of uncoupling between blood flow and metabolism in major cerebral arterial occlusion.

In patients who have major cerebral arterial occlusive disease with low perfusion, a decrease in cerebral metabolism may be reflected by a reduction in contralateral cerebellar blood flow (crossed cerebellar hypoperfusion). This study was done to investigate whether comparison of the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion could be used to estimate the degree of uncoupling of cerebral blood flow and metabolism on the basis of a single blood flow study. We used positron emission tomography before and after reconstructive vascular surgery to evaluate regional blood flow and oxygen metabolism in the cerebral and cerebellar cortexes of 11 patients with major cerebral arterial occlusive disease. Preoperatively these patients had cortical blood flow asymmetry in the middle cerebral artery territory. The degree of crossed cerebellar hypoperfusion had no relation to the extent of cerebral blood flow asymmetry but was significantly correlated with the extent of asymmetry in cerebral oxygen metabolism. The preoperative extent of asymmetry in the cerebral oxygen extraction fraction and the postoperative improvement of asymmetry in cerebral blood flow were correlated with the preoperative difference between the severity of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion. The difference between the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion can be used to estimate the degree of uncoupling between blood flow and metabolism, which can in turn predict the postoperative improvement of cerebral blood flow asymmetry. We suggest that this approach may be a simple means of estimating the relative uncoupling between blood flow and metabolism from a single blood flow study in patients who have major cerebral arterial occlusive disease with low perfusion.

MR imaging signal response to sustained stimulation in human visual cortex.

The response of signal intensity to transient (on-off) motor and sensory stimulation has been well studied; however, the dependence of signal response on the duration of stimulus requires further characterization. The objective of this study was to determine the time course of signal response in the human visual cortex to prolonged, sustained stimulation and to examine possible contributory physiologic mechanisms. Nine healthy volunteers underwent magnetic resonance (MR) imaging during sustained visual stimulation with light-proof binocular goggles. With photic stimulation, activation was observed in all subjects as an increase in signal intensity of the visual cortex. With sustained stimulation, a gradual decrease in signal intensity was subsequently observed, with progression toward an apparent steady state. Correlation with positron emission tomographic, MR spectroscopic, and visual evoked-potential data suggests that the initial uncoupling of cerebral blood flow and oxidative metabolism with a neuronal activation burst may represent a transient phenomenon. This quick-response phase may proceed to an equilibrium coupling of flow and oxidative metabolism, with a gradual normalization of venous deoxyhemoglobin levels and signal intensity.

Hypothermic cerebral reperfusion and recovery from ischemia

The effect of transient postischemic hypothermia (30 degrees C) on recovery of cerebral blood flow (CBF), oxygen consumption (CMRO2) and somatosensory-evoked potentials (SEPs) was determined in anesthetized dogs. Ischemia was produced for 20 min by intracranial pressure (ICP) elevation while core temperature was lowered by cooling externalized blood. Epidural temperature was controlled at 37.6 +/- 0.2 degrees C during ischemia, lowered to 30.0 +/- 0.1 degrees C during the first hour of reperfusion, and then rewarmed to 38.0 +/- 0.1 degrees C in experimental dogs (n = 8) and maintained at 38.0 +/- 0.1 degrees C in control dogs (n = 8). ICP was lower throughout reperfusion in experimental as compared with control animals. By 240 min of reperfusion, CBF was approximately 70% of control in both groups. CMRO2 was 60% of preischemic values in control animals and 74% in experimental animals (P = 0.077). A persistent uncoupling of CBF and CMRO2 was observed throughout reperfusion only in the control group. Recovery of SEP amplitude was significantly improved in the experimental group (26 vs. 11% of preischemic values). These data suggest that transient hypothermia reduces ICP and facilitates recovery of electrophysiological function after cerebral ischemia.

Uncoupling of blood flow and oxygen metabolism in the cerebellum in type 3 Gaucher disease

Cerebral blood flow and oxygen metabolism were measured in a fourteen-year-old girl with type 3 Gaucher disease by using positron emission tomography (PET). Cranial CT and MRI showed only mild brain atrophy. PET demonstrated uncoupling of cerebral blood flow and oxygen metabolism, that is, a mild increase of cerebral blood flow and a reduction of oxygen extraction fraction and cerebral metabolic rate of oxygen only in the cerebellum. Although the mechanism is unknown, the above finding may reflect the underlying pathogenesis of the disorder. PET seems to be more sensitive than CT and MRI in detecting some functional abnormalities in the affected structures. However, further investigations must be done before concluding that this finding is unique to type 3 Gaucher disease.