Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts

Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [¹⁸F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose—one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.     

Effects of cerebral angiomas on perifocal and remote tissue: a multivariate positron emission tomography study.

BACKGROUND AND PURPOSE: Using multitracer positron emission tomography, I investigated regional hemodynamic and metabolic changes in both perifocal and remote tissues of cerebral angiomas, with special reference to steal phenomena. METHODS: In 22 patients (14 with arteriovenous malformations and eight with cavernomas) cerebral blood flow, cerebral blood volume, mean vascular transit time, cerebral metabolic rate for oxygen, oxygen extraction fraction, cerebral metabolic rate for glucose, and glucose extraction fraction were measured using standard positron emission tomographic methods. Twelve patients also had their cerebral glucose metabolism assessed during psychophysical activation. Regions of interest representing the angioma, perifocal and remote tissues, contralateral mirror regions, and standard brain regions were analyzed. RESULTS: There were no significant changes in hemodynamic variables or oxygen metabolism in the ipsilateral cerebral hemisphere, but ipsilateral glucose metabolism was reduced both at rest (p less than 0.01) and during activation (p less than 0.05). Glucose (p less than 0.001) and oxygen (p less than 0.001) metabolism in regions of perifocal tissue with low blood flow were decreased, with substrate extraction fractions showing no increase to compensate for insufficient blood flow. Functional recruitment of the cortex overlying the angioma beyond its periphery and supplied by the same arterial branches was subnormal (p less than 0.05) despite relatively unchanged hemodynamics in this tissue compartment. CONCLUSIONS: These data suggest that dysfunction of the cortex supplied by arterial branches also feeding the vascular malformation is related to neuronal deafferentation, while the proportionate decrease in blood flow and metabolism of perifocal tissue may be ascribed to neuronal loss in chronically hypoperfused areas, rather than to persistent hemodynamic steal effects.     

Positron emission tomographic evaluation of histological malignancy in gliomas using oxygen-15 and fluorine-18-fluorodeoxyglucose

HEADTOME III, a high resolution PET, has been employed using 15O and 18F labelled pharmaceuticals to evaluate histological malignancy of gliomas preoperatively. PET study was applied on eighteen preoperative gliomas including two recurrent cases. Haemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rates for oxygen (rCMRO2) and glucose (rCMRGI) were measured in the viable portion of the tumour, and the contralateral grey and white matter. In the tumour region, rCBF and rCBV were variable and unrelated to grades of tumour malignancy. rCMRO2 and rOEF values reduced significantly (p less than 0.01) relative to the contralateral brain tissue. The average rCMRGI values was 3.00 +/- 1.06 mg 100 ml-1 min-1 (mean +/- SD) for 7 low grade gliomas (grade II), and 5.91 +/- 3.61 mg 100 ml-1 min-1 for 11 high grade gliomas (grade III and IV). These results would support that anaerobic glycolysis increased in the metabolism of gliomas with malignancy. In comparison with normal volunteers, rCBF, rCMRO2, and rCMRGI values in the contralateral grey matter of gliomas were markedly reduced (p less than 0.01, p less than 0.05, p less than 0.01, respectively) possibly due in part to raised intracranial pressure and depressed cerebral functional activity, so that rOEF was increased to a level of approximately 0.5.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progressive derangement of periinfarct viable tissue in ischemic stroke.

Sixteen patients were studied by multitracer positron emission tomography (PET) within 6-48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13-25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 +/- 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 +/- 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke.     

Effect of withdrawal from chronic naltrexone on regional cerebral oxygen consumption in the cat

This investigation determined the effects of withdrawal from chronic naltrexone administration on average and regional cerebral blood flow, oxygen extraction and oxygen consumption. The relationship between the effects of withdrawal from chronic administration of this opiate receptor antagonist, which may increase the numbers of postsynaptic opiate receptors, and these parameters was investigated. Fourteen adult mongrel cats were administered subcutaneous injections of 1 mg/kg naltrexone HCl or 1 ml 0.9% saline twice daily for 21 days. Two days later, regional cerebral blood flow was monitored using radioactively tagged microspheres. The animals were sacrificed and prepared for microspectrophotometric analysis of regional cerebral venous and arterial oxygen saturation. Regional cerebral oxygen consumption was calculated as the product of cerebral blood flow and oxygen extraction for each area examined. After 2 days of withdrawal from chronic naltrexone treatment, the blood pressure, heart rate and blood gas parameters did not change significantly when compared to saline-treated animals. Average cerebral blood flow was significantly increased from 47.9 +/- 3.4 ml/min/100 g (mean +/- S.E.M.) in the control group to 80.3 +/- 6.5 (ml/min/100 g) in the chronic naltrexone-treated group. Flow was significantly increased in the cortex, lenticulate nuclei, thalamus and pons. Neither average cerebral oxygen consumption, which increased slightly, nor cerebral oxygen extraction, which decreased slightly, were significantly altered by treatment. The distribution of flow among the examined regions was, however, significantly altered in the animals 2 days after receiving chronic naltrexone injections. These changes were not restricted to brain regions dense in neuronal opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertension induced changes in cerebral capillary permeability to water are mediated by afferent neuronal connections from the carotid sinus to the brain

The effects of acute opiate receptor stimulation on regional cerebral oxygen consumption and blood flow were examined in 9 regions of the artificially respired, alpha-chloralose-anesthetized cat. Regional cerebral arterial and venous oxygen saturation were examined microspectrophotometrically and regional cerebral blood flow was monitored using radioactively tagged microspheres (15 +/- 3 micron in diameter). Oxygen consumption was calculated as the product of flow and oxygen extraction. In 8 cats, after control cerebral blood flow was obtained, and in 8 experimental cats after this same measurement was obtained before and 40 min after the administration of 1.5 mg/kg morphine sulfate; the cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic and diastolic blood pressure were significantly decreased by treatment. The heterogeneity of venous oxygen saturation was significantly reduced by morphine. Average cerebral blood flow, oxygen extraction and consumption were not altered significantly by morphine. Regional cerebral blood flow in the hypothalamus, thalamic oxygen extraction, and hypothalamic and thalamic oxygen consumption were significantly decreased by treatment. This low dose of morphine may produce changes in cerebral neuronal and/or synthetic activity which lowers oxygen consumption in some regions rich in opiate receptors, while not affecting overall brain oxygen supply or consumption.     

Reflectance spectrophotometric measurement of in vivo local oxygen consumption in the cerebral cortex

A simple method was developed to measure in vivo local oxygen consumption quantitatively in the brain cortex. Reflectance spectra of tissue hemoglobin at the brain's surface were measured for assessment of both local tissue hemoglobin content and its oxygen saturation. Local oxygen consumption was calculated from the spectral changes of tissue hemoglobin during complete cessation of blood flow by compression of the cortical surface in the suprasylvian gyrus with the tip of an optic probe. This procedure was performed without any brain damage and only took approximately 5 s. The calculated local oxygen consumption during this short period of compression remained constant for a few seconds. Then, it decreased rapidly, although the local tissue hemoglobin was not completely deoxygenated. The value of local cerebral oxygen consumption obtained by this method was 3.02 +/- 0.61 mL O2/100 g brain/min; it was not influenced by the change in systemic blood pressure. The effect of pentobarbital on cerebral oxygen consumption was also studied. At the stage of burst and suppression on electrocorticogram, cerebral oxygen consumption decreased significantly (p less than 0.001) to 1.03 +/- 0.07 mL O2/100 g brain/min.     

Temporal evolution of regional energy metabolism following focal cerebral ischemia in the rat

Focal cerebral ischemia in the rat was induced by occlusion of the left middle cerebral artery. The temporal evolution of regional energy metabolism was studied over the 14 days consequent to the induction of ischemia in the frontal, cingulate, parietal, and occipital cortices as well as in the striatum. Regional concentrations of adenosine triphosphate (ATP), phosphocreatine, and lactate and, in addition, glucose and the cerebral/plasma glucose ratio (C/P) were measured in the hemispheres both ipsilateral and contralateral to the occlusion. Two hours after middle cerebral artery occlusion, the biochemical changes were severe in the striatum and moderate in cortical regions. Later on (at 24 and 48 h), an overall aggravated metabolic status was noted while lactate declined and glucose markedly increased. These latter biochemical changes likely indicate a marked inhibition of the rate of glucose utilization. At 48 h, the energy reserves (ATP, phosphocreatine) of parietal cortex no longer equaled those of other cortical regions, but abruptly fell to the levels found in the striatum without any increase in lactate level. Finally, at 7 and 14 days, the levels of the various metabolites in most cortical regions returned toward control values, although signs of a depressed glucose metabolism remained. However, in both striatum and parietal cortex, ATP and phosphocreatine concentrations, although higher than those observed at 48 h, remained significantly decreased. Our present biochemical study permits the classification of these selected brain regions into three categories. First there are those that are outside the area of infarction: the frontal, cingulate, and occipital cortices. These regions show little temporal evolution of brain energy metabolism but, notwithstanding, they are regions in which glucose use would appear to be greatly depressed. Second is a region considered to be the focus of infarction: the striatum. The caudate-putamen is a region with early and profound metabolic disturbances with no final restitution. Last is the region of metabolic penumbra--the parietal cortex, in which there is a time-related exacerbation of the consequences of middle cerebral occlusion in the rat.     

Effect of locus coeruleus stimulation on regional cerebral oxygen consumption in the cat

Regional cerebral oxygen consumption was determined during stimulation of the intra-axial noradrenergic pathway to quantitate the metabolic effects of this manipulation on cerebral oxygen extraction, cerebral blood flow (CBF) and its regional distribution. Regional arterial and venous oxygen saturation were examined microspectrophotometrically. Regional CBF was examined using radioactively tagged microspheres (15 +/- 3 microns in diameter). Oxygen consumption was calculated as the regional product of CBF and oxygen extraction. Bipolar concentric electrodes were stereotaxically implanted bilaterally in the locus coeruleus of alpha-chloralose anesthetized, artificially respired adult mongrel cats. The control group was killed after hemodynamic and CBF measurements were taken. The experimental group was sacrificed after these same measurements were taken before and during 10 min of bilateral locus coeruleus stimulation. The cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic blood pressure was significantly increased during treatment. The heterogeneity of venous oxygen saturation was significantly reduced by stimulation. Average CBF and oxygen consumption were significantly decreased to 57% and 59% of control, respectively. Oxygen consumption was significantly reduced in the hypothalamus from 1.5 +/- 0.3 to 0.9 +/- 0.3 ml O2/min/100 g and from 3.5 +/- 0.9 to 1.2 +/- 0.4 ml O2/min/100 g in the cerebellum by treatment. Changes in the neuronal and/or synthetic cerebral activity produced regional decreases in cerebral oxygen consumption and secondarily altered CBF. These changes are probably due to interaction of the intraparenchymal noradrenergic pathways with other systems or processes in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of morphine on regional cerebral oxygen consumption and supply

The effects of acute opiate receptor stimulation on regional cerebral oxygen consumptilon and blood flow were examined in 9 regions of the artificially respired, α-chloralose-anesthetized cat. Regional cerebral arterial and venous oxygen saturation were examined microspectrophotometrically and regional cerebral blood flow was monitored using radioactively tagged microspheres (15 ± 3 μm in diameter). Oxygen consumption was calculated as the product of flow and oxygen extraction. In 8 cats, after control cerebral blood flow was obtained, and in 8 experimental cats after this same measurement was obtained before and 40 min after the administration of 1.5 mg/kg morphine sulfate; the cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic and diastolic blood pressure were significantly decreased by treatment. The heterogeneity of venous oxygen saturation was significantly reduced by morphine. Average cerebral blood flow, oxygen extraction and consumption were not altered significantly by morphine. Regional cerebral blood flow in the hypothalamus, thalamic oxygen extraction, and hypothalamic and thalamic oxygen consumption were significantly decreased by treatment. This low dose of morphine may produce changes in cerebral neuronal and/or synthetic activity which lowers oxygen consumption in some regions rich in opiate receptors, while not affecting overall brain oxygen supply or consumption.     

Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients

The purpose of this study was to explore the feasibility of obtaining magnetic resonance-measured cerebral metabolic rate of oxygen utilization (MR-CMRO(2)) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 +/- 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion-weighted, perfusion-weighted, and multiecho gradient-echo/spin-echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO(2) was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2-weighted images and the "penumbra" obtained from the tp1 perfusion-weighted image-defined lesion were coregistered onto tp1 CMRO(2) maps. CMRO(2) values in the region of brain that eventually infarcted were reduced to 0.40 +/- 0.24 of the respective region on the contralateral hemisphere. The "salvaged penumbra" defined by the area of mismatch between the final infarct and the tp1 perfusion-weighted lesion demonstrated an average CMRO(2) value of 0.55 +/- 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR-CMRO(2) noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients.     

Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients

Values of regional cerebral oxygen extraction ratio and oxygen utilisation obtained with the oxygen-15 steady-state inhalation technique have been found to be overestimated due to the signal from intravascular oxygen-15. A previously described method to correct for this intravascular component has been applied to a series of studies on normal subjects, and on brain tumour and stroke patients. With this correction the regional cerebral oxygen extraction ratio in normals becomes comparable to the global values previously reported with arteriovenous sampling techniques. Within the lesions of brain tumour and stroke patients, the corrections have been found to be variable and often substantial. It is concluded that failure to apply this correction may result in major errors in the values for regional oxygen extraction ratio and oxygen utilisation. This is especially true when the regional blood flow and oxygen extraction ratio of a tissue is low and regional blood volume is high.     

Comparison of Glucose Metabolism and Cerebral Blood Flow During Cortical Motor Activation

Regions of cerebral cortex activated in normal subjects making simple, repetitive, voluntary wrist movements were studied with positron emission tomography (PET). The regional cerebral metabolic rate of glucose utilization was studied with 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG), and regional cerebral blood flow was studied with ¹⁵O-labeled water. No significant activation was found with the cerebral metabolic rate studies. Studies of regional cerebral blood flow showed significant activation of the contralateral sensorimotor cortex region of 42%, of the ipsilateral sensorimotor cortex region of 19%, and of the medial frontal cortex of 30% compared with the resting state. Increases in blood flow in the contralateral sensorimotor cortex and medial frontal cortex were visible on every activated scan. Measurement of regional cerebral blood flow seems to be more sensitive than regional cerebral metabolic rate of glucose utilization for studying cortical activation with voluntary movement.     

Neurobiology of non-REM sleep in depression: further evidence for hypofrontality and thalamic dysregulation

OBJECTIVE: Sleep disturbances characterize depression and may reflect the abnormal persistence of brain activity from wakefulness into non-REM sleep. The goal of this study was to investigate the functional neuroanatomical correlates of non-REM sleep relative to presleep wakefulness in depressed patients and healthy subjects. METHOD: Twelve medication-free depressed patients and 13 healthy subjects underwent polysomnography and [(18)F]fluorodeoxyglucose positron emission tomography scans during presleep wakefulness and non-REM sleep. Statistical parametric mapping contrasts were performed to detect differences in relative regional cerebral glucose metabolism between presleep wakefulness and non-REM sleep in each group as well as interactions across states and between groups. RESULTS: Relative to healthy subjects, depressed patients showed less of a decrease in relative regional cerebral glucose metabolism from presleep wakefulness to non-REM sleep in the left and right laterodorsal frontal gyri, right medial prefrontal cortex, right superior and middle temporal gyri, insula, right posterior cingulate cortex, lingual gyrus, striate cortex, cerebellar vermis, and left thalamus. CONCLUSIONS: Patterns of relative regional cerebral glucose metabolism changes from presleep wakefulness to non-REM sleep differ in healthy subjects and depressed patients. Specifically, the transition from wakefulness to non-REM sleep was characterized by the relative persistence of elevated metabolic activity in frontoparietal regions and thalamus in depressed patients compared with healthy subjects. These findings suggest that abnormal thalamocortical network function may underlie sleep anomalies and complaints of nonrestorative sleep in depressed patients.     

Postoperative hemodynamic and metabolic changes in patients with subarachnoid hemorrhage

Positron emission tomography was performed using an oxygen-15 gas inhalation technique to measure regional cerebral blood flow, metabolic rate for oxygen, oxygen extraction fraction, and cerebral blood volume in 13 patients with subarachnoid hemorrhage during the period of delayed vasospasm after surgery as well as in 10 volunteers as controls. Compared with the controls, the patients showed decreased hemoglobin concentration and decreased total arterial oxygen content due to postoperative hemodilution. Global reductions in the metabolic rate for oxygen and in the tissue oxygen supply were noted even in the apparently normal cortex of the patients in spite of adequate blood flow and adequate oxygen extraction fraction. In addition, regional reductions in blood flow and in perfusion reserve were seen in the cortical territory corresponding to cerebral vasospasm. Our results indicate that two processes are involved in the pathophysiology of cerebral vasospasm: 1) generalized impairment of oxygen metabolism with a reduced tissue oxygen supply, even in the apparently normal cortex, and 2) additional impairment of regional perfusion in the territory of vasospasm.     

Decompressive hemicraniectomy in a new cat model. Methodological description of the PET study protocol

Positron emission tomography (PET) is increasingly used to quantify regional hemodynamic and metabolic changes in different animal models. Most of these (multitracer) studies provided important early data on already functionally altered brain tissue, indicating selective vulnerability by a large variability in the functional blood flow threshold of individual neurons. To fill the gap between experimental studies at early time points and rather late clinical studies at well-defined but singular time points, we repeatedly measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction rate and cerebral metabolic rate of glucose (CMRglc) in three cats before and up to 28 h after decompressive hemicraniectomy on normal brain tissue. Decompressive hemicraniectomy in the cat decreased CBF, and to a lesser extent CMRO2 and CMRglc 2 h after surgical intervention in normal brain tissue that last for at least 1 day. CBF significantly decreased (p < 0.01) and oxygen extraction fraction (OEF) (p < 0.05) significantly increased. CMRO2 and CMRglc decreased only in regions with most severe CBF reduction. These effects remained for at least a day irrespective of corrective sustaining cranioplasty. The method and data analysis is decreased and discussed in detail in the presented protocol. In conclusion, serial positron emission tomography studies are best suited to repeatedly and non-invasively demonstrate circulatory and biochemical changes by surgical interventions in normal brain tissue for at least one day. The transition of normal brain tissue into misery-perfused or non-viable regions can be followed over time. Such state-of-the-art imaging modalities as sequential high-resolution positron emission tomography provide insight into the dynamic of regional pathophysiology and may thus further justify the development of rational therapeutic strategies for decompressive hemicraniectomy, especially for disease with focal disturbances in cerebral blood flow.     

The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts

Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 +/- 2.5 ml/100 gm/min (mean +/- SEM) and was in every patient lower than that in C (33.1 +/- 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 +/- 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 +/- 1.5). In Group I, region I showed a CMRGlc(N)/CMRO2 ratio of 0.22 +/- 0.06 and a CpH of 6.83 +/- 0.06. In Group 2, the same ratio in the region I was 0.58 +/- 0.09 and the CpH was 7.12 +/- 0.05. The CMRGlc (N)/CMRO2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRO2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed.     

Positron emission tomography (PET) study in patients with meningiomas

Regional hemocirculation and metabolism were evaluated in five patients with meningiomas using positron emission tomography (PET). Histological diagnoses were: two cases of meningotheliomatous type, one hemangiopericytic type, one fibroblastic type, and one transitional type. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rates of oxygen (rCMRO2) and glucose (rCMRG1) were measured with 15O2, C15O. 15O2, and 18F-fluorodeoxyglucose tracers. For the quantitative analysis, regions of interest were delineated on tumors, the peritumoral region, and the contralateral gray matter in comparison with age-corresponding 5 malignant gliomas and 5 normal volunteers. Tumor hemocirculatory parameters (rCBF: 57.2 +/- 22.6 ml/100 ml/min, rCBV: 7.95 +/- 3.27 ml/100 ml, mean + SD, n = 5) were markedly higher than those of the contralateral gray matter (p less than 0.05 by a Student-t test). The high values were consistent with angiographic findings of tumor staining and with abundant tumor vessels demonstrated by pathological examination. rCMRO2 was 2.15 +/- 0.80 ml/100 ml/min, which were comparable to those of the contralateral gray matter. Tumor rCMRG1 showed 4.76 +/- 2.37 mg/100 ml/min; the values of two cases were similar to the respective gray matter. The raised metabolic rate (rCMRO2/rCMRG1) therefore suggests rather aerobic glycolysis as compared with gliomas. Low rOEF (0.26 +/- 0.16) reveals an excessive blood flow beyond oxygen demand of the tumor. In the peritumoral regions, rCBF and metabolism fell slightly but rOEF reached a level similar to the contralateral gray matter, possibly due to hemocirculatory stasis caused by intracranial hypertension; in contrast, an unmatched reduction of rCBF and rCMRO2 implies tumor cells infiltration in gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography

A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilisation, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilisation paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[18F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects.     

Cerebral blood flow and oxygen consumption in cortical spreading depression

We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.