Metabolic control of resting hemispheric cerebral blood flow is oxidative,not glycolytic

Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO₂) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO₂, CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO₂ was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO₂: arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO₂ and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.     

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with 15O PET

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF_b), CBV, OEF, cerebral oxygen metabolic rate (CMRO₂), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by ¹⁵O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF_b (>47.6 mL/100 mL/min, n = 7) was associated with normal CBF_b/CBV, increased CBV, decreased OEF, and normal CMRO₂. Low CBF_b (<31.8 mL/100 mL/min, n = 9) was associated with decreased CBF_b/CBV, increased CBV, increased OEF, and decreased CMRO₂. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF_b regions with normal CPP, which has not been described in previous studies.     

Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with ¹⁵O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C_aO₂), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO₂ was independent of Hb concentration. Oxygen delivery defined as a product of C_aO₂ and CBF (C_aO₂ CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO₂. The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the ¹⁵O PET data in clinical practice.     

Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO₂ and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.     

Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep

A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole‐brain cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2‐relaxation‐under‐spin‐tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase‐contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age‐ and sex‐matched control volunteers (n = 39) during natural sleep to assess whole‐brain CMRO₂, CBF, OEF, and arousal from sleep scores. Results showed that whole‐brain CMRO₂ and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp 38:2532–2539, 2017. © 2017 Wiley Periodicals, Inc.     

Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural–vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO₂), and flow–metabolism coupling (ΔCBF/ΔCMRO₂), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO₂ increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow–metabolism coupling (ΔCBF/ΔCMRO₂) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO₂ in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO₂ responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural–vascular coupling.     

Smoking normalizes cerebral blood flow and oxygen consumption after 12-hour abstention

Acute nicotine administration stimulates [¹⁴C]deoxyglucose trapping in thalamus and other regions of rat brain, but acute effects of nicotine and smoking on energy metabolism have rarely been investigated in human brain by positron emission tomography (PET). We obtained quantitative PET measurements of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO₂) in 12 smokers who had refrained from smoking overnight, and in a historical group of nonsmokers, testing the prediction that overnight abstinence results in widespread, coupled reductions of CBF and CMRO₂. At the end of the abstention period, global grey-matter CBF and CMRO₂ were both reduced by 17% relative to nonsmokers. At 15 minutes after renewed smoking, global CBF had increased insignificantly, while global CMRO₂ had increased by 11%. Regional analysis showed that CMRO₂ had increased in the left putamen and thalamus, and in right posterior cortical regions at this time. At 60 and 105 minutes after smoking resumption, CBF had increased by 8% and CMRO₂ had increased by 11-12%. Thus, we find substantial and global impairment of CBF/CMRO₂ in abstaining smokers, and acute restoration by resumption of smoking. The reduced CBF and CMRO₂ during acute abstention may mediate the cognitive changes described in chronic smokers.     

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex

OBJECTIVES—Silentbrain infarction (SBI) is of growing interest as a possible risk factorfor symptomatic stroke. Although morphological characteristics of SBIhave been well defined, their characteristic patterns of cerebral bloodflow (CBF) and metabolism are in dispute. The purpose of this study wasto elucidate CBF and metabolism in patients with SBI in relation tosymptomatic stroke.
METHODS—The patientsunderwent PET and were separated into three groups; control group (Cgroup), with no lesions on CT (n=9, mean age 57), SBI group, with noneurological signs or history of stroke, but with ischaemic lesions onCT (n=9, mean age 63), and brain infarction group (BI group), withneurological deficits and compatible CT lesions in the area supplied byperforating arteries (n=19, mean age 56). Regional CBF, oxygenextraction fraction (OEF), cerebral metabolic rate for oxygen(CMRO₂), and cerebral blood volume (CBV) were measured by PET.
RESULTS—Mean valuesfor CBF to the cerebral cortex and deep grey matter were lower in theSBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively)and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) thanin the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively).Although mean CMRO₂ of deep grey matter (2.36 (SD 0.52)ml/100 g/min) was significantly decreased in the SBI group comparedwith the C group (2.76 (SD 0.480), p<0.01), CMRO₂ of thecortical area was as well preserved in the SBI patients (2.36 (SD0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increaseof mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively).
CONCLUSIONS—Patientswith SBI showed decreased CBF and CMRO₂ in deep greymatter. On the other hand, decreased CBF with milder increased OEF,resulting in preserved CMRO₂ in the cerebral cortexindicates the presence of occult misery perfusion, suggesting thatpatients with SBI have reduced cerebral perfusional reserves.

     

Striatal and cortical BOLD,blood flow,blood volume,oxygen consumption,and glucose consumption changes in noxious forepaw electrical stimulation

Recent reports showed noxious forepaw stimulation in rats evoked an unexpected sustained decrease in cerebral blood volume (CBV) in the bilateral striatum, whereas increases in spike activity and Fos-immunoreactive cells were observed. This study aimed to further evaluate the hemodynamic and metabolic needs in this model and the sources of negative functional magnetic resonance imaging (fMRI) signals by measuring blood oxygenation-level-dependent (BOLD), cerebral-blood-flow (CBF), CBV, and oxygen-consumption (i.e., cerebral metabolic rate of oxygen (CMRO₂)) changes using an 11.7-T MRI scanner, and glucose-consumption (i.e., cerebral metabolic rate of glucose (CMRglc)) changes using micro-positron emission tomography. In the contralateral somatosensory cortex, BOLD, CBF, CBV, CMRO₂ (n=7, P<0.05), and CMRglc (n=5, P<0.05) increased. In contrast, in the bilateral striatum, BOLD, CBF, and CBV decreased (P<0.05), CMRO₂ decreased slightly, although not significantly from baseline, and CMRglc was not statistically significant from baseline (P>0.05). These multimodal functional imaging findings corroborate the unexpected negative hemodynamic changes in the striatum during noxious forepaw stimulation, and support the hypothesis that striatal hemodynamic response is dominated by neurotransmitter-mediated vasoconstriction, overriding the stimulus-evoked fMRI signal increases commonly accompany elevated neuronal activity. Multimodal functional imaging approach offers a means to probe the unique attributes of the striatum, providing novel insights into the neurovascular coupling in the striatum. These findings may have strong implications in fMRI studies of pain.     

Post-operative changes of cerebral circulation and metabolism in the acute stage of low-grade aneurysmal subarachnoid hemorrhage

Abstract

Objective: Pre- and post-operative cerebral circulation and metabolism were evaluated in patients with low-grade acute aneurysmal subarachnoid hemorrhage (SAH) who underwent early surgery to investigate the effects on brain dysfunction.

Methods: Positron emission tomography (PET) was performed to measure the regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF) and cerebral blood volume in four patients (one male and three females, mean age: 60.3 years) with low-grade SAH within 30 hours of onset. Post-operative PET was performed on the seventh post-operative day. No patient suffered clinical deterioration during the study. Pre-operative PET scans demonstrated significant global reduction of CBF and CMRO₂, compared to 16 normal control subjects, and no significant change in OEF. CBF and CMRO₂ reduction post-operatively improved to the normal control values. Post-operative OEF was significantly increased compared to the normal control value.

Conclusions: Patients with low-grade SAH have impairment of cerebral circulation and metabolism in the acute period, which improves after surgery. Early surgery for low-grade SAH, necessary to avoid rerupture of the aneurysm, did not worsen the impairment of cerebral circulation and metabolism. However, measures to protect the brain from perioperative damage are necessary to achieve the optimum outcome.     

Acute effect of glucose on cerebral blood flow,blood oxygenation,and oxidative metabolism

While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose‐sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole‐brain metabolism is not completely understood. Several recent reports have elucidated the long‐term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O₂ (CMRO₂) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO₂ was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post‐ingestion, the amount of CMRO₂ reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO₂, CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. Hum Brain Mapp 36:707–716, 2015. © 2014 Wiley Periodicals, Inc .     

Accounting for the role of hematocrit in between‐subject variations of MRI‐derived baseline cerebral hemodynamic parameters and functional BOLD responses

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between‐subject variation of Hct thus causes variation in task‐based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T₁ values by comparison with the conventional lab test. Together with CBF measured using phase‐contrast MRI, this noninvasive estimation of Hct, instead of using a population‐averaged Hct value, enabled more individual determination of oxygen delivery (DO₂), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂). The inverse correlation of CBF and Hct explained about 80% of between‐subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO₂ to maintain constant CMRO₂. Furthermore, we compared the relationships of visual task‐evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%–33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%–22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344–353, 2018. © 2017 Wiley Periodicals, Inc.     

Ischemic brain metabolism in patients with chronic cerebrovascular disease: Increased oxygen extraction fraction and cerebrospinal fluid lactate

The aim of the present study is to elucidate the existence of chronically ischemic metabolism concomitant with misery perfusion of the brain in patients with chronic cerebrovascular disease. For this purpose, we measured cerebral blood flow (CBF) and oxygen metabolism by positron emission tomography (PET) and also determined cerebrospinal fluid (CSF) lactate as an indicator of the ischemic brain metabolism. Twenty-eight patients with chronic ischemic stroke and transient ischemic attack (TIA), who had angiographically occlusive (n = 11), stenotic (n = 10), and nonstenotic changes (n = 7) of the carotid artery and/or the intracranial major artery, were selected for this study. CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO₂), and cerebral blood volume (CBV) were determined by PET, and CSF lactate and pyruvate were determined by enzymatic method in the patients with various grades of stenotic changes of the carotid artery. There were no significant differences in PET parameters and CSF variables among the groups of the occlusive, stenotic, and nonstenotic carotid artery. However, CSF lactate was correlated negatively with mean bilateral hemispheric (m)CBF (R² = 0.229, P<.01), positively with mOEF (R² = 0.278, P<.005) and more highly with mCMRO₂/CBF (absolute extraction of oxygen content to the brain) (R² = 0.473, P<.0001) in all patients. There was no correlation between CSF lactate and mCMRO₂ or mCBV. None of the cases in the nonstenotic group showed mOEF greater than 0.45, or mCMRO₂/CBF greater than 7.9 vol%, while 80% of the cases in the stenotic group and 82% of the cases in the occlusive group showed mOEF and mCMRO₂/CBF exceeding the above-mentioned values, respectively. The present findings, that increased mOEF and mCMRO₂/CBF were significantly correlated with increased CSF lactate, indicate the brain to be in a metabolically ischemic state or increased anaerobic glycolysis with oxygen metabolism maintained in patients with chronic ischemic stroke.     

Cerebral blood flow and oxygen uptake, and cerebrospinal fluid biochemistry in severe coma

Thirty-eight patients in coma due to head trauma, cerebrovascular accidents, hypoxia, hypoglycaemia, or barbiturate intoxication, and 15 cases of brain death were studied. Cerebral metabolic rate of oxygen (CMRO₂) was obtained from the arteriovenous oxygen difference and cerebral blood flow (CBF) measured by intra-arterial ¹³³Xenon method. If hypothermia and CNS depressants were excluded, CMRO₂ below one-third of normal was incompatible with regaining of consciousness, but this was seen in only three comatose patients. Irrespective of the clinical outcome (death, vegetative survival, or recovery), CMRO₂ values of one-third to two-thirds of normal were seen in the majority of coma patients. CMRO₂ measurements were of no practical value to predict the prognosis in coma, even when the effect of temperature and sedatives were considered. In brain death the CBF studies gave indirect evidence of cerebral circulatory arrest. The cerebrospinal fluid (CSF) was obtained for analysis of lactate, pyruvate, and bicarbonate in 29 cases. Increased CSF lactate levels were found in all groups except barbiturate intoxication. The finding of a negative correlation between CSF bicarbonate and log CBF suggests that the CSFpH determines the wide range of CBF in coma.     

Preserved acetazolamide reactivity in lacunar patients with severe white-matter lesions: 15O-labeled gas and H2O positron emission tomography studies

Limited evidence exists on the relationships between severity of white-matter lesions (WMLs) and cerebral hemodynamics in patients without major cerebral artery disease. To examine changes of cerebral blood flow (CBF), oxygen metabolism, and vascular reserve capacity associated with severity of WML in patients with lacunar stroke, we used a positron emission tomography (PET). Eighteen lacunar patients were divided into two groups according to the severity of WMLs, assessed by Fazekas classification; grades 0 to 1 as mild WML group and grades 2 to 3 as severe WML group. Rapid dual autoradiography was performed with ¹⁵O-labeled gas-PET followed by ¹⁵O-labeled water-PET with acetazolamide (ACZ) challenge. Compared with the mild WML group, the severe WML group showed lower CBF (20.6±4.4 versus 29.9±8.2 mL/100 g per minute, P=0.008), higher oxygen extraction fraction (OEF) (55.2±7.4 versus 46.7±5.3%, P=0.013), and lower cerebral metabolic rate of oxygen (CMRO₂) (1.95±0.41 versus 2.44±0.42 mL/100 g per minute, P=0.025) in the centrum semiovale. There were no significant differences in the ACZ reactivity between the two groups (48.6±22.6% versus 42.5±17.2%, P=0.524). Lacunar patients with severe WMLs exhibited reduced CBF and CMRO₂, and increased OEF in the centrum semiovale. The ACZ reactivity was preserved in both patients with severe and mild WMLs in each site of the brain.     

Cyclosporine A,FK506, and NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression

Cortical spreading depression (CSD) is associated with mitochondrial depolarization, increasing intracellular Ca²⁺, and the release of free fatty acids, which favor opening of the mitochondrial permeability transition pore (mPTP) and activation of calcineurin (CaN). Here, we test the hypothesis that cyclosporine A (CsA), which blocks both mPTP and CaN, ameliorates the persistent reduction of cerebral blood flow (CBF), impaired vascular reactivity, and a persistent rise in the cerebral metabolic rate of oxygen (CMRO₂) following CSD. In addition to CsA, we used the specific mPTP blocker NIM811 and the specific CaN blocker FK506. Cortical spreading depression was induced in rat frontal cortex. Electrocortical activity was recorded by glass microelectrodes, CBF by laser Doppler flowmetry, and tissue oxygen tension with polarographic microelectrodes. Electrocortical activity, basal CBF, CMRO₂, and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD; the rise in CMRO₂ was unchanged. Our data suggest that blockade of mPTP formation and CaN activation may prevent persistent CBF reduction and vascular dysfunction after CSD.     

Misery perfusion caused by cerebral hypothermia improved by vasopressor administration

Abstract

Therapeutic cerebral hypothermia is widely used for the treatment of severe head injury and cerebral ischemia. The effects of cerebral hypothermia on the cerebral blood flow (CBF) and metabolism, and cerebral vasculature in the normal brain were investigated. Thirty-four adult cats were divided into four groups. CBF was monitored by hydrogen clearance. Arteriovenous oxygen difference (AVD02) and cerebral venous oxygen saturation (ScvO₂) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO₂) and cerebral vascular resistance (CVR) were calculated. The cerebral blood volume (CBV) was measured using technetium-99m-labeled human serum albumin in 12 cats. Deep cerebral temperature was cooled from 37° C to 25° C using a water-circulating blanket. In the hypothermia group (Croup A: n = 10), CBF (51.2 ± 8.3 ml 100 g^–1 min^–1 at 37° C) decreased with lower brain temperature (6.1 ±2.7 at 25°C). CMRO₂ (2.24 ± 0.75ml 100g^–1 min^–1 at 37° C) was also decreased (0.52 ±0.20 at25°C). AVDO₂ (4.3 ± 1.0 ml 100 g^–1 min^–1 at 37° C) increased significantly at 31°C (6.6 ± 1.8; p < 0.05) and ScvO₂ (67.8 ± 7.9% at 37°C) decreased significantly at 29° C (53.7± 9.7; p < 0.05). CBV (5.3 ± 1.2% at 37°C) decreased significantly at 29°C (3.7± 1.0;p < 0.05) and CVR (3.2 ±0.7 mmHg ml^–1 100g^–1 min^–1 at 37° C) increased significantly at 29° C (13.8 ±5.2; p < 0.01). The combined effect of hypothermia with vasopressor (noradrenalin) (Croup B: n = 6) or barbiturate (thiopental) administration (Croup C: n = 6) on the cerebral metabolic parameters were also examined. Hypothermia with noradrenalin administration significantly improved the ischemic parameters (AVDO₂ was 4.7± 1.4ml 100g min^–1 at 31°C and ScvO₂ was 72.2±6.4% at 29°C). However, hypothermia with barbiturate administration did not improve these metabolic parameters. These results suggest that hypothermia may cause vasoconstriction and misery perfusion in the brain. This potential risk of relative ischemia can be avoided by combination with vasopressor administration. [Neurol Res 1999; 21: 585–592]     

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington’s disease

Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO₂ during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO₂ responses were observed in premanifest and early manifest HD patients compared to controls (P < 0.001), correlating with the CAG-Age Product scores in these patients (R² = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO₂ response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.     

Cerebral blood flow and metabolism of hyperperfusion after cerebral revascularization in patients with moyamoya disease

In moyamoya disease (MMD), surgical revascularization may be complicated with postoperative hyperperfusion. We analyzed cerebral perfusion and metabolism using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) before and after bypass surgery on 42 sides of 34 adult patients with MMD. In seven cases (16.7%) with symptomatic hyperperfusion, diagnosed by qualitative ¹²³I-iodoamphetamine (IMP) SPECT, a subsequent PET study during postoperative subacute stages revealed significantly increased cerebral blood flow (CBF) from 34.1±8.2 to 74.3±12.8 mL/100 g per minute (P<0.01), a persistent increase in cerebral blood volume (CBV) from 5.77±1.67 to 7.01±1.44 mL/100 g and a significant decrease in oxygen extraction fraction (OEF) from 0.61±0.09 to 0.40±0.08 (P<0.01). Mean absolute CBF values during symptomatic hyperperfusion were more than the normal control +2 standard deviations, the predefined criteria of PET. Interestingly, two patients with markedly increased cerebral metabolic rate of oxygen (CMRO₂) at hyperperfusion were complicated with postoperative seizure. Among preoperative PET parameters, increased OEF was the only significant risk factor for symptomatic hyperperfusion (P<0.05). This study revealed that symptomatic hyperperfusion in MMD is characterized by temporary increases in CBF >100% over preoperative values caused by prolonged recovery of increased CBV.     

Method for rapid MRI quantification of global cerebral metabolic rate of oxygen

A recently reported quantitative magnetic resonance imaging (MRI) method denoted OxFlow has been shown to be able to quantify whole-brain cerebral metabolic rate of oxygen (CMRO₂) by simultaneously measuring oxygen saturation (S_vO₂) in the superior sagittal sinus and cerebral blood flow (CBF) in the arteries feeding the brain in 30 seconds, which is adequate for measurement at baseline but not necessarily in response to neuronal activation. Here, we present an accelerated version of the method (referred to as F-OxFlow) that quantifies CMRO₂ in 8 seconds scan time under full retention of the parent method''s capabilities and compared it with its predecessor at baseline in 10 healthy subjects. Results indicate excellent agreement between both sequences, with mean bias of 2.2% (P=0.18, two-tailed t-test), 3.4% (P=0.08, two-tailed t-test), and 2.0% (P=0.56, two-tailed t-test) for S_vO₂, CBF, and CMRO₂, respectively. F-OxFlow''s potential to monitor dynamic changes in S_vO₂, CBF, and CMRO₂ is illustrated in a paradigm of volitional apnea applied to five of the study subjects. The sequence captured an average increase in S_vO₂, CBF, and CMRO₂ of 10.1±2.5%, 43.2±9.2%, and 7.1±2.2%, respectively, in good agreement with literature values. The method may therefore be suited for monitoring alterations in CBF and S_vO₂ in response to neurovascular stimuli.