The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia.

PurposeTo compare mean global cerebral blood flow (CBF) measured by phase‐contrast mapping magnetic resonance imaging (PCM MRI) and by 15O‐H2O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique.Materials and MethodsSame‐day measurements of CBF by 15O‐H2O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one‐tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume‐segmented 3D T 1‐weighted anatomical MR‐scan.ResultsMean CBF was 34.9 ± 3.4 mL/100 g/min measured by 15O‐H2O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R2 = 0.44), although values obtained by PCM MRI were higher compared to 15O‐H2O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively).ConclusionThis study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to 15O‐H2O PET, probably related to methodological bias. Level of Evidence: 3J. Magn. Reson. Imaging 2017;45:692–699.

Studies of the resting brain measurements of cerebral blood flow (CBF) show large interindividual and regional variability, but the metabolic basis of this variability is not fully established. The aim of the present study was to reassess regional and interindividual relationships between cerebral perfusion and glucose metabolism in the resting brain. Regional quantitative measurements of CBF and cerebral metabolic rate of glucose (CMR) were obtained in 24 healthy young men using dynamic [O]HO and [F]fluorodeoxyglucose positron emission tomography (PET). Magnetic resonance imaging measurements of global oxygen extraction fraction (gOEF) and metabolic rate of oxygen ([Formula: see text]) were obtained by combined susceptometry-based sagittal sinus oximetry and phase contrast mapping. No significant interindividual associations between global CBF, global CMR, and [Formula: see text] were observed. Linear mixed-model analysis showed a highly significant association of CBF with CMR regionally. Compared with neocortex significantly higher CBF values than explained by CMR were demonstrated in infratentorial structures, thalami, and mesial temporal cortex, and lower values were found in the striatum and cerebral white matter. The present study shows that absolute quantitative global CBF measurements appear not to be a valid surrogate measure of global cerebral glucose or oxygen consumption, and further demonstrates regionally variable relationship between perfusion and glucose metabolism in the resting brain that could suggest regional differences in energy substrate metabolism. NEW & NOTEWORTHY Using method-independent techniques the study cannot confirm direct interindividual correlations of absolute global values of perfusion with oxygen or glucose metabolism in the resting brain, and absolute global perfusion measurements appear not to be valid surrogate measures of cerebral metabolism. The ratio of both perfusion and oxygen delivery to glucose metabolism varies regionally, also when accounting for known methodological regional bias in quantification of glucose metabolism.

The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p<0.00001) and 45.2 (7.3)% (p<0.00001). Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8)% (p<0.00001) and 46.1 (10.4)% (p<0.00001). In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4)% (p = 0.029); low-dose Epoetin beta: 73.1 (17.8)% (p = 0.039)). In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is unknown. EPO may improve the efficiency of oxidative metabolism and has neuroprotective properties against hypoxic injuries in animal models. We aimed to investigate the effect of recombinant human EPO (rHuEPO) administration on healthy cerebral metabolism in humans during normoxia and during metabolic stress by inhalation of 10% O hypoxic air. Twenty-four healthy men participated in a two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU·kg body wt·day) for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and metabolic rate of glucose (CMR) were measured with positron emission tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral lactate concentration were measured by magnetic resonance imaging and spectroscopy. Low-dose treatment increased hemoglobin and was associated with a near-significant decrease in CBF during baseline normoxia. High-dose treatment caused no change in CBF. Neither treatment had an effect on normoxia CMR, [Formula: see text], or lactate concentration or an effect on the cerebral metabolic response to inhalation of hypoxic air. In conclusion, the study found no evidence for a direct effect of rHuEPO on cerebral metabolism. NEW & NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission tomography that administration of erythropoietin does not have a substantial direct effect on healthy human resting cerebral blood flow or effect on cerebral glucose and oxygen metabolism. Also, administration of erythropoietin did not have a direct effect on the metabolic response to acute hypoxic stress in healthy humans, and a suggested neuroprotective effect from erythropoietin is therefore likely not a direct effect of erythropoietin on cerebral metabolism.