Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging

The regional cerebral blood flow (rCBF) and metabolic rate for glucose (rCMRGlc) are associated with functional activity of the neural cells. The present work reports a comparison study between rCBF and rCMRGlc in a normal population as a function of age. 10 young (25.9+/-5.6 years) and 10 old (65.4+/-6.1 years) volunteers were similarly studied at rest. In each subject, rCBF and rCMRGlc were measured in sequence, during the same session. Both rCBF and rCMRGlc values were found to decrease from young (mean rCBF=43.7 ml/100 g per min; mean rCMRGlc=40.6 micromol/100 g per min) to old age (mean rCBF=37.3 ml/100 g per min; mean rCMRGlc=35.2 micromol/100 g per min), resulting in a drop over 40 years of 14.8% (0.37%/year) and 13.3% (0.34%/year), respectively. On a regional basis, the frontal and the visual cortices were observed to have, respectively, the highest and the lowest reduction in rCBF, while, for rCMRGlc, these extremes were observed in striatum and cerebellum. Despite these differences, the ratio of rCBF to rCMRGlc was found to have a similar behavior in all brain regions for young and old subjects as shown by a correlation coefficient of 88%. This comparative study indicates a decline in rCBF and rCMRGlc values and a coupling between CBF and CMRGlc as a function of age.     

Lowered cerebral glucose utilization in amyotrophic lateral sclerosis

Regional cerebral metabolic rates for glucose (rCMRGlc) were analyzed in 19 studies of 12 patients with amyotrophic lateral sclerosis (ALS) by positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose. In the 8 ALS patients with upper motor neuron signs, the mean cortical rCMRGlc was significantly lower than in 11 age-matched control subjects (p less than 0.01). The degree of hypometabolism correlated with the duration of the clinical signs and extended throughout the cortex and basal ganglia, but not to the cerebellum. Of the 4 such patients who had repeat PET scans, 3 demonstrated significant subsequent reduction in the rCMRGlc, corresponding to the worsening of the clinical picture. In contrast, 4 ALS patients with disease confined to lower motor neurons and 3 patients with lower motor neuron disease from old paralytic poliomyelitis had normal or near-normal rCMRGlc throughout the brain. Because histological evidence shows no generalized neuronal cell loss in the cortex of ALS patients, including in some cases the primary motor regions, the demonstration of severe generalized hypometabolism in structurally normal cortex indicates that some cortical neurons exist in a state of neuronal nonfunction, rather than cell death, and that anatomoclinical correlations may be more complex. The data also indicate that ALS with upper motor neuron involvement extends beyond the corticospinal tracts and differs in cortical function from the ALS confined to lower motor neurons or the other lower motor neuron disorders.     

PET和TCD对阿耳茨海默病早期诊断的研究

目的 利用正电子发射计算机断层扫描（ｐｏｓｉｔｒｏｎ ｅｍｉｓｓｉｏｎ ｔｏｍｏｇｒａｐｈｙ,ＰＥＴ）和经颅多普勒超声（ｔｒａｎｓｃｒａｎｉａｌ ｄｏｐｐｌｅｒ,ＴＣＤ）相结合的方法探讨阿耳茨海默病（Ａｌｚｈｅｉｍｅｒ’ｓ ｄｉｓｅａｓｅ,ＡＤ）的早期诊断,以及ＡＤ与脑血液供应之间的关系。方法 ２０例可疑ＡＤ患者和２０例正常对照行ＰＥＴ、ＴＣＤ以及临床神经心理量表检查,对局部脑区葡萄糖代谢率（ｒｅ     

Measurement of carotid blood flow in man and its clinical application

With the use of a new ultrasonic volume flow meter (VFM), over 8000 measurements of common carotid blood flow were made in 120 normal control subjects and 550 patients with various neurological disease. The accuracy of the flow meter in measuring blood flow on an experimental model ranged from 93 to 97%. In normal subjects, common carotid blood flow varies with age. It increased from newborn to age 20 and gradually decreased thereafter. In normal healthy subjects, the flow varies within +/- 6.7% (2SD) at one sitting (intrasession) and +/- 21.2% (2SD) from week to week (intersession study). Carotid blood flow varies linearly with PaCO2 and increased markedly in response to endotracheal intubation. In healthy adults, the flow ratio between the two common carotid arteries is 1.07 +/- 0.052. This ratio increases in patients with transient ischemic attacks to 1.28 +/- 0.23 (p less than 0.05) and in patients with intracranial space occupying lesions to 1.46 +/- 0.39, (p less than 0.01). In 26 consecutive cases of carotid endarterectomies, the preoperative common carotid blood volume flow was 5.1 +/- 1.0 cc/sec. All cases preoperatively had at least 30% stenosis and ranged from 30 to 100% stenosis. The carotid blood volume was significantly increased post-operatively (p less than 0.001). The overall accuracy in detecting carotid and cerebral arterial disease is 89% with sensitivity of 96% and the specificity of 71%. Our clinical experience indicates that this device is not only a valuable noninvasive diagnostic tool for evaluation of carotid disease but also appears to be useful in assessing cerebral blood flow.     

The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.     

Changed pattern of regional glucose metabolism during yoga meditative relaxation

Using positron emission tomography (PET), measurements of the regional cerebral metabolic rate of glucose (rCMRGlc) are able to delineate cerebral metabolic responses to external or mental stimulation. In order to examine possible changes of brain metabolism due to Yoga meditation PET scans were performed in 8 members of a Yoga meditation group during the normal control state (C) and Yoga meditative relaxation (YMR). Whereas there were intraindividual changes of the total CMRGlc, the alterations were not significant for intergroup comparison; specific focal changes or changes in the interhemispheric differences in metabolism were also not seen; however the ratios of frontal vs. occipital rCMRGlc were significantly elevated (p less than 0.05) during YMR. These altered ratios were caused by a slight increase of frontal rCMRGlc and a more pronounced reduction in primary and secondary visual centers. These data indicate a holistic behavior of the brain metabolism during the time of altered state of consciousness during YMR.     

Cerebellar blood flow and metabolism in cerebral hemisphere infarction

Positron emission tomography was used to study the effect of supratentorial infarction on cerebellar metabolic rate for oxygen and cerebellar blood flow. In a control group of patients, the mean cerebellar metabolic rate for oxygen was 2.97 +/- 0.11 (standard error of the mean [SEM] ) ml-1 . min-1 . hg-1 and mean cerebellar blood flow was 41.1 +/- 1.5 ml . min-1 . hg-1. No significant right-left asymmetry in either cerebellar metabolic rate for oxygen or cerebellar blood flow was noted. Patients with frontal lobe infarction showed 16.8 +/- 1.8% (cerebellar metabolic rate for oxygen) and 19.6 +/- 2.1% (cerebellar blood flow) differences between cerebellar hemispheres, with the hemisphere contralateral to the cerebral infarction having the lower values. These differences were highly significant (p less than 0.001). In addition, cerebellar blood flow and cerebellar metabolic rate for oxygen were significantly decreased in the ipsilateral cerebellar hemisphere (metabolism: 2.13 +/- 0.19 ml . min-1 . hg-1; p less than 0.002; blood flow: 35.2 +/- 2.4 ml . min-1 . hg-1; p less than 0.05). Patients with parietooccipital infarction also showed a significant bilateral decrease in cerebellar metabolic rate for oxygen (2.43 +/- 0.11 ml . min-1 . hg-1) and cerebellar blood flow (34.6 +/- 2.5 ml . min-1 . hg-1) relative to control subjects, but no significant cerebellar asymmetry. Our findings demonstrate a general depression of cerebellar blood flow and metabolism from cerebral hemisphere infarction unrelated to the site of infarction as well as a specific depression occurring contralateral to infarction involving the frontal lobe. These are among the first quantitative data concerning regional cerebellar metabolic rates for oxygen and cerebellar blood flow in humans.     

Blood flow and metabolism during and after repeated partial brain ischemia in neonatal piglets.

BACKGROUND AND PURPOSE: Our investigation sought to determine whether neonatal brain ischemic vascular and metabolic effects were altered by repeated episodes of ischemia. METHODS: We studied twelve piglets using in vivo magnetic resonance spectroscopy to obtain multiple, simultaneous measurements of cerebral blood flow and phosphorylated metabolites from the same tissue volume. The relationship between cerebral blood flow and energy metabolism was examined over a range of reduced cerebral blood flow (90-10% of control). Three episodes of partial ischemia were studied, each lasting 10 minutes and separated by 45 minutes. RESULTS: During each interval of ischemia, plots of the percent reduction in cerebral blood flow versus the percent change in phosphorylated metabolites (phosphocreatine, inorganic phosphorus) or unit change in intracellular pH did not differ in slope and intercept. The relationship between beta-ATP and cerebral blood flow during repeated ischemia revealed similar slopes, but a lower intercept during the third interval of ischemia (p = 0.029). After ischemia, cerebral blood flow was reduced as a function of the severity of the preceding ischemia. After each interval of ischemia, phosphocreatine and intracellular pH were unchanged from preischemic values. Inorganic phosphorus remained elevated after ischemia (117 +/- 16 and 118 +/- 11% of control, p less than 0.005, following the first and second intervals of ischemia), and beta-ATP was restored to progressively lower values (92 +/- 10 and 83 +/- 11% of control, p less than 0.025). Calculated free ADP decreased after ischemia and correlated with the postischemic level of beta-ATP (r = 0.63, p = 0.001). CONCLUSIONS: These results demonstrate that the relationship between cerebral blood flow and metabolism was reasonably preserved during repeated partial ischemia. However, following ischemia, alterations occurred in both cerebral blood flow and metabolism. These alterations may reflect a relative inhibition of ATP production by metabolic regulators such as ADP on either glycolysis or oxidative phosphorylation or both.     

Quantitative assessment of cerebral blood volume by single-photon emission computed tomography.

We implemented a technique for measuring regional cerebral blood volume using single-photon emission computed tomography and in vivo technetium-99m-labeled red blood cells and then evaluated it in nine normal human volunteers (controls) and seven patients with bilateral occlusion or severe stenosis of the internal carotid artery. We also measured regional cerebral blood flow using single-photon emission computed tomography and intravenous xenon-133 in the same subjects. We studied regional cerebral blood flow, regional cerebral blood volume, and their ratio before and after the intravenous injection of 1 g acetazolamide. Mean +/- SD baseline regional cerebral blood volume was higher in the patients than in the controls (4.1 +/- 0.6 versus 3.2 +/- 0.3 ml/100 g, p less than 0.01), and mean +/- SD baseline regional cerebral blood flow was lower in the patients than in the controls (40.5 +/- 11 versus 55.6 +/- 11 ml/100 g/min, p less than 0.05). Acetazolamide induced similar mean +/- SD increases in regional cerebral blood volume in both the controls and the patients (0.3 +/- 0.1 and 0.3 +/- 0.2 ml/100 g), while the mean +/- SD regional cerebral blood flow reactivity was significantly less in the patients than in the controls (12.6 +/- 7.6 versus 24.5 +/- 9.6 ml/100 g/min, p less than 0.05). Our study shows that single-photon emission computed tomography can provide quantitative estimates of both regional cerebral blood volume and regional cerebral blood flow in humans.     

Noninvasive assessment of CO2-induced cerebral vasomotor response in normal individuals and patients with internal carotid artery occlusions

To evaluate the CO2-induced vasomotor reactivity of the cerebral vasculature, relative changes of blood flow velocity within the middle cerebral artery were measured by transcranial Doppler ultrasonography during normocapnia and various degrees of hypercapnia and hypocapnia. We studied 40 normal individuals and 40 patients with unilateral and 15 patients with bilateral internal carotid artery occlusions. When blood flow velocity changes as percent of normocapnic values were plotted against end-tidal CO2 volume percent, a biasymptotic curve (a tangent-hyperbolic function) gave the best fit of the scattergram. The distance between the upper and lower asymptotes was defined as cerebral vasomotor reactivity. In the normal individuals, mean +/- SD vasomotor reactivity was 85.63 +/- 15.96%. In patients with internal carotid artery occlusions, vasomotor reactivity was significantly lower than normal on both the occluded (mean 45.2%, median 50.4%; p less than 0.0001) and the nonoccluded (mean +/- SD 67.7 + 13.3%, p less than 0.01) sides in the unilateral group and on both sides (mean +/- SD 36.6 +/- 15.9% and 44.9 +/- 24.6%, p less than 0.0001) in the bilateral group. The difference between vasomotor reactivity for symptomatic and asymptomatic unilateral occlusions was also highly significant (mean 37.6% and 62.9%, p less than 0.006). Vasomotor reactivity was also significantly lower in patients with low-flow infarctions on computed tomography than in patients with normal scans (mean +/- SD 36.7 +/- 25% and 60.2 +/- 16.9%, p less than 0.008). A striking association of low-flow infarctions, ischemic ophthalmopathy, and hypostatic transient ischemic attacks was found with vasomotor reactivities of less than 34% or even paradoxical reactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/- 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.     

Hemodilution increases cerebral blood flow in acute ischemic stroke

We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc of dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.     

Glucose-associated alterations in ischemic brain metabolism of neonatal piglets.

BACKGROUND AND PURPOSE: During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates. METHODS: Two groups of animals (n = 12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258 +/- 97 mg% [mean +/- SD]) with modest hypoglycemia (plasma glucose concentration, 62 +/- 23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (beta-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group. RESULTS: During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of beta-ATP (p = 0.011) and had a smaller increase in inorganic phosphorus (p less than 0.001). At cerebral blood flow less than 50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to less than 6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals. CONCLUSIONS: ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue.     

Endogenous platelet activating factor does not modulate blood flow and metabolism in normal rat brain

Both platelet activating factor and eicosanoids participate in the cerebrovascular response to ischemia. Eicosanoids also modulate cerebrovascular tone under normal physiologic circumstances, but a similar role for platelet activating factor has not been investigated. Therefore, using 16 rats, we studied the effects of the platelet activating factor receptor blockers BN 52021 (10 mg/kg, n = 4 or 30 mg/kg, n = 2) and WEB 2086 (5 mg/kg, n = 6) on global cerebral blood flow and the cerebral metabolic rate for oxygen and compared them with the effect of indomethacin (10 mg/kg, n = 4). Neither antagonist altered cerebral blood flow (112 +/- 16 and 107 +/- 14 ml/100 g/min at baseline versus 108 +/- 16 and 105 +/- 18 ml/100 g/min after BN 52021 and WEB 2086, respectively). In contrast, indomethacin significantly (p less than 0.05) decreased cerebral blood flow from 106 +/- 8 to 69 +/- 4 ml/100 g/min. No treatment altered the cerebral metabolic rate for oxygen compared with baseline. These data suggest that in normal rat brain, concentrations of platelet activating factor, unlike those of eicosanoids, are subthreshold and do not modulate cerebral blood flow or the cerebral metabolic rate for oxygen.     

Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy

Cerebral ammonia metabolism was studied in five control subjects and five patients with severe liver disease exhibiting minimal hepatic encephalopathy. The arterial ammonia concentration in the control subjects was 30 +/- 7 mumol/L (mean +/- SD) and 55 +/- 13 mumol/L in the patients (p less than 0.01). In the normal subjects, the whole-brain values for cerebral blood flow, cerebral metabolic rate for ammonia, and the permeability-surface area product for ammonia were 0.58 +/- 0.12 ml g-1 min-1 0.35 +/- 0.15 mumol 100 g-1 min-1, and 0.13 +/- 0.03 ml g-1 min-1, respectively. In the patients, the respective values were 0.46 +/- 0.16 ml g-1 min-1 (not different from control), 0.91 +/- 0.36 mumol 100 g-1 min-1 (p less than 0.025), and 0.22 +/- 0.07 ml g-1 min-1 (p less than 0.05). The increased permeability-surface area product of the blood-brain barrier permits ammonia to diffuse across the blood-brain barrier into the brain more freely than normal. This may cause ammonia-induced encephalopathy even though arterial ammonia levels are normal or near normal and explain the emergence of toxin hypersensitivity as liver disease progresses. Greater emphasis on early detection of encephalopathy and aggressive treatment of minimal hyperammonemia may retard the development of ammonia-induced complications of severe liver disease.     

Compensatory mechanisms in patients with asymptomatic carotid artery occlusion

Twelve patients with asymptomatic occlusion of one (n = 8) or both (n = 4) internal carotid arteries were examined by positron emission tomography (PET) and transcranial Doppler ultrasound. PET measurements included the determination of the regional cerebral blood flow (rCBF), oxygen extraction ratio (rOER), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose consumption (rCMRGlc). Transcranial Doppler ultrasound (TCD) was used to determine the pathways and efficacy of collateralization via the circle of Willis and included spectrum analysis of flow velocities within the middle and anterior cerebral arteries as well as vasoreactivity tests. In correspondence with ultrasound evidence of a haemodynamically effective intracranial collateral circulation no significant differences between patients and controls were observed for rOER, rCMRO2 and rCMRGlc, but rCBF was globally reduced. Furthermore, in all patients with unilateral carotid occlusion PET excluded side asymmetries of any parameter studied. In contrast, flow velocity parameters measured by TCD were significantly reduced ipsilateral and significantly increased contralateral to the carotid obstruction. Vasodilative capacities, however, remained preserved even in the territory of the occluded carotid system. These data indicate that patients with asymptomatic carotid occlusion compensate by haemodynamic and not by metabolic mechanisms in contrast to symptomatic patients.     

Epilepsy patients treated with antiepileptic drug therapy exhibit compromised ocular perfusion characteristics

PURPOSE: Reduced cerebral blood flow and decreased cerebral glucose metabolism have been identified in patients with epilepsy treated with antiepileptic drug (AED) therapy. The purpose of this study was to determine whether ocular haemodynamics are similarly reduced in patients with epilepsy treated with AEDs. METHODS: Scanning laser Doppler flowmetry was used to measure retinal capillary microvascular flow, volume, and velocity in the temporal neuroretinal rim of 14 patients diagnosed with epilepsy (mean age, 42.0 +/- 0.9 years). These values were compared with those of an age- and gender-matched normal subject group (n = 14; mean age, 41.7 +/- 0.3 years). Student's unpaired two-tailed t tests were used to compare ocular blood-flow parameters between the epilepsy and normal subject groups (p < 0.05; Bonferroni corrected). RESULTS: A significant reduction in retinal blood volume (p = 0.001), flow (p = 0.003), and velocity (p = 0.001) was observed in the epilepsy group (13.52 +/- 3.75 AU, 219.14 +/- 76.61 AU, and 0.77 +/- 0.269 AU, respectively) compared with the normal subject group (19.02 +/- 5.11 AU, 344.03 +/- 93.03 AU, and 1.17 +/- 0.301 AU, respectively). Overall, the percentage mean difference between the epilepsy and normal groups was 36.31% for flow, 28.92% for volume, and 34.19% for velocity. CONCLUSIONS: Patients with epilepsy exhibit reduced neuroretinal capillary blood flow, volume, and velocity compared with normal subjects. A reduction in ocular perfusion may have implications for visual function in people with epilepsy.     

Quantification of regional cerebral blood flow with IMP-SPECT. Reproducibility and clinical relevance of flow values

Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine (IMP-SPECT) was performed in 14 normal volunteers (seven men and seven women aged 25.1 +/- 5.3 years) and 29 patients with cerebrovascular disease (18 men and 11 women aged 54.1 +/- 13.7 years). The fluid microsphere model was used to estimate cerebral blood flow (CBF). Normal subjects were scanned twice, 1 week apart, to determine the reproducibility of the CBF estimates. Hemispheric blood flow (hCBF) was calculated as the mean of regional cerebral blood flow (rCBF) values in 16 gray matter regions per hemisphere. In normal subjects mean hCBF was 68 ml/100 g/min. The highest rCBF was found in the occipital cortex, followed by the frontal, temporal, and parietal cortexes. CBF values were reproducible (p less than 0.001 except the right thalamic region, where p less than 0.01). Intraindividual variation ranged between 0.3% and 15%. Women exhibited significantly higher (16%, p less than 0.02) CBF than men. Patients were subdivided into groups with reversible (n = 19) and persistent (n = 10) symptoms. Significant hCBF differences between the affected and the contralateral hemispheres were recorded only in the group with reversible symptoms (p less than 0.005), whereas the group with persistent symptoms showed a significant bilateral decrease of hCBF compared with normal subjects and patients with reversible symptoms. Focal CBF was significantly lower in patients with completed stroke than in patients with transient symptoms (p less than 0.001). Our results indicate that IMP-SPECT can be used for the routine estimation of CBF in normal and pathologic states.     

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)     

Abnormal cerebral glucose metabolism in long-term survivors of childhood acute lymphocytic leukemia

Chemotherapy and radiation treatment of the central nervous system may cause delayed neurotoxicity in children with acute lymphocytic leukemia. We evaluated 12 long-term survivors of childhood leukemia using [18F]fluorodeoxyglucose positron emission tomography, computed tomography scans, clinical neurological examinations, and neuropsychological tests. Regional cerebral metabolic rate for glucose (rCMRGlc) values for white matter were lower in the older long-term survivors (greater than 18 years old) treated with cranial radiation and intrathecal chemotherapy than in normal control subjects or survivors who had been treated with intrathecal chemotherapy alone. The ratio of white matter: cortex rCMRGlc values was lower than control values in the long-term survivors treated with cranial radiation and intrathecal chemotherapy, regardless of age, but not in those treated with intrathecal chemotherapy alone. By contrast, thalamic rCMRGlc values were lower than control values in older survivors regardless of treatment, and the ratio for thalamus:cortex rCMRGlc values was lower in all the treatment groups than in the control subjects. The highest rCMRGlc values were found in the youngest children, indicating an important effect of age on cerebral glucose metabolism. No neuropsychological deficits were identified in patients treated only with intrathecal chemotherapy; however, lower IQ scores were found in the long-term survivors who had been treated with cranial radiation and intrathecal chemotherapy. Treatment of the central nervous system with cranial radiation and intrathecal chemotherapy may cause prolonged alterations in white-matter and thalamic rCMRGlc, which may permit the identification and assessment of neurotoxicity in long-term survivors of acute lymphocytic leukemia by [18F]fluorodeoxyglucose positron emission tomography.