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.     

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.     

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.     

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.

     

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.     

Early Derangements in Oxygen and Glucose Metabolism Following Head Injury: The Ischemic Penumbra and Pathophysiological Heterogeneity

Introduction  Conclusive evidence of cerebral ischemia following head injury has been elusive. We aimed to use ¹⁵O and ¹⁸Fluorodeoxyglucose positron emission tomography (PET) to investigate pathophysiological derangements following head injury. Results   Eight patients underwent PET within 24 h of injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO₂), oxygen extraction fraction (OEF), and cerebral glucose metabolism (CMRglc). Physiological regions of interest (ROI) were generated for each subject using a range of OEF values from very low (<10), low (10–30), normal range (30–50), high (50–70), and critically high (≥70%). We applied these ROIs to each subject to generate data that would examine the balance between blood flow and metabolism across the injured brain independent of structural injury. Discussion   Compared to the normal range, brain regions with higher OEF demonstrate a progressive CBF reduction (P < 0.01), CMRO₂ increase (P < 0.05), and no change in CMRglc, while regions with lower OEF are associated with reductions in CBF, CMRO₂, and CMRglc (P < 0.01). Although all subjects demonstrate a decrease in CBF with increases in OEF > 70%, CMRO₂ and CMRglc were generally unchanged. One subject demonstrated a reduction in CBF and small fall in CMRO₂ within the high OEF region (>70%), combined with a progressive increase in CMRglc. Conclusions  The low CBF and maintained CMRO₂ in the high OEF ROIs is consistent with classical cerebral ischemia and the presence of an ‘ischemic penumbra’ following early head injury, while the metabolic heterogeneity that we observed suggests significant pathophysiological complexity. Other mechanisms of energy failure are clearly important and further study is required to delineate the processes involved.     

Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO₂) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S_vO₂) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO₂ in physiologic units. In addition, microvascular tissue oxygenation (StO₂) and indices of microvascular CBF (BFI) and CMRO₂ (CMRO_2i) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO₂ were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O₂/minute per 100 g, respectively. These CBF and CMRO₂ values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global S_vO₂, CBF, and CMRO₂ with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R²=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.     

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.     

Baseline CBF,and BOLD,CBF, and CMRO2 fMRI of visual and vibrotactile stimulations in baboons

Neurovascular coupling associated with visual and vibrotactile stimulations in baboons anesthetized sequentially with isoflurane and ketamine was evaluated using multimodal functional magnetic resonance imaging (fMRI) on a clinical 3-Tesla scanner. Basal cerebral blood flow (CBF), and combined blood-oxygenation-level-dependent (BOLD) and CBF fMRI of visual and somatosensory stimulations were measured using pseudo-continuous arterial spin labeling. Changes in stimulus-evoked cerebral metabolic rate of oxygen (CMRO₂) were estimated using calibrated fMRI. Arterial transit time for vessel, gray matter (GM), and white matter (WM) were 250, 570, and 823 ms, respectively. Gray matter and WM CBF, respectively, were 107.8±7.9 and 47.8±3.8 mL per 100 g per minute under isoflurane, and 108.8±10.3 and 48.7±4.2 mL per 100 g per minute under ketamine (mean±s.e.m., N=8 sessions, five baboons). The GM/WM CBF ratio was not statistically different between the two anesthetics, averaging 2.3±0.1. Hypercapnia evoked global BOLD and CBF increases. Blood-oxygenation-level-dependent, CBF, and CMRO₂ signal changes by visual and vibrotactile stimulations were 0.19% to 0.22%, 18% to 23%, and 4.9% to 6.7%, respectively. The CBF/CMRO₂ ratio was 2.9 to 4.7. Basal CBF and fMRI responses were not statistically different between the two anesthetics. This study establishes a multimodal fMRI protocol to probe clinically relevant functional, physiological and metabolic information in large nonhuman primates.     

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.     

CBF/CBV maps in normal volunteers studied with 15O PET: a possible index of cerebral perfusion pressure

Local cerebral perfusion pressure (CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow (CBF) to cerebral blood volume (CBV) can be used as an index of the local CPP. In this study, we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of ¹⁵O positron emission tomography. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by H₂ ¹⁵O bolus injection for CBF measurement and by C¹⁵O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization. Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum (19.3 ± 5.2/min), followed by the putamen (18.2 ± 3.9), pons (16.4 ± 4.6), thalamus (14.5 ± 3.3), cerebral cortices (13.2 ± 2.4), and centrum semiovale (11.5 ± 2.1). The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.     

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.     

Differential responses in CBF and CBV to cocaine as measured by fMRI: Implications for pharmacological MRI signals derived oxygen metabolism assessment

Introduction

Cognitive performance-induced brain oxygen metabolism has been successfully measured by functional magnetic resonance imaging (fMRI) in human studies. The measurement of the cerebral metabolic rate of oxygen consumption (CMRO₂) is typically achieved by assuming a fixed coupling of cerebral blood flow (CBF) and cerebral blood volume (CBV) and by performing a separate experiment to assess the vascular response to a hypercapnic challenge. Psychoactive drugs may have directly effect on the cerebral vasculature, potentially confounding the interpretation of pharmacological MRI (phMRI) data. In this study, we tested the assumptions of the standard CMRO₂ calculation following the administration of cocaine, in order to test the validity of this measurement in phMRI studies. The initial transient state and later steady state CBF and CBV responses to a hypercapnic challenge were measured.

Methods

CBF and CBV responses were directly measured by fMRI using continuous arterial spin-labeling (ASL) and contrast-enhanced fMRI, respectively. The coupling between changes in CBF and CBV during a hypercapnic challenge was examined under normal conditions and following the administration of cocaine.

Results

A decoupling of changes in CBF and CBV was observed during the transient state immediately following the administration of cocaine, and an altered coupling of CBF and CBV was found during the steady state after cocaine injection.

Discussion

These data suggest caution in interpreting CMRO₂ measurements from phMRI studies and may also lead to an improved understanding of the complex neuronal and vascular mechanisms of drug action.     

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.     

Oxygen extraction fraction and acetazolamide reactivity in symptomatic carotid artery disease

Objective: It has been proposed that cerebral blood flow (CBF) response to acetazolamide may be reduced according to the degree of autoregulatory vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the CBF response may be absent in regions with increased OEF where vasodilation may be maximal in response to reduced perfusion pressure. The objective of this study was to test this hypothesis.

Methods: Positron emission tomography (PET) was used to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide was measured. The correlation between the change in CBF during acetazolamide administration and the baseline value of OEF in the affected hemisphere was examined.

Results: The baseline OEF value was inversely and non-linearly correlated with the percentage change in CBF during acetazolamide administration (R² = 0.25, p = 0.02). There was an upward trend of OEF with diminishing acetazolamide response below a critical level around zero response. Acetazolamide response less than 6.65% over baseline (sensitivity 100%, specificity 89%, positive predictive value 50%, negative predictive value 100%) was established as most helpful in predicting abnormally high OEF.

Conclusions: The inverse, non-linear relationship between OEF and CBF response to acetazolamide suggests that these two measurements may not identify haemodynamic impairment in the same patients.

     

Noninvasive optical measures of CBV,StO2, CBF index,and rCMRO2 in human premature neonates' brains in the first six weeks of life

With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD‐NIRS) measures of cerebral tissue oxygenation (StO₂) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF_ix) to test the validity of the CBV‐CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO₂) with or without the CBF_ix measurement. We measured 11 premature neonates (28–34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO₂ during the first six weeks of life while CBV remains stable, and a steady increase in CBF_ix. rCMRO₂ estimated from FD‐NIRS remains constant but shows wide interindividual variability. rCMRO₂ calculated from FD‐NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD‐NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO₂, CBF, and rCMRO₂ in the premature brain, facilitating individual follow‐up and comparison among patients. A stable CBV‐CBF relationship may not be valid for premature neonates. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Calibrated MRI to evaluate cerebral hemodynamics in patients with an internal carotid artery occlusion

The purpose of this study was to assess whether calibrated magnetic resonance imaging (MRI) can identify regional variances in cerebral hemodynamics caused by vascular disease. For this, arterial spin labeling (ASL)/blood oxygen level-dependent (BOLD) MRI was performed in 11 patients (65±7 years) and 14 controls (66±4 years). Cerebral blood flow (CBF), ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) were evaluated. The CBF was 34±5 and 36±11 mL/100 g per minute in the ipsilateral middle cerebral artery (MCA) territory of the patients and the controls. Arterial spin labeling CVR was 44±20 and 53±10% per 10 mm Hg ▵EtCO₂ in patients and controls. The BOLD CVR was lower in the patients compared with the controls (1.3±0.8 versus 2.2±0.4% per 10 mm Hg ▵EtCO₂, P<0.01). The OEF was 41±8% and 38±6%, and the CMRO₂ was 116±39 and 111±40 μmol/100 g per minute in the patients and the controls. The BOLD CVR was lower in the ipsilateral than in the contralateral MCA territory of the patients (1.2±0.6 versus 1.6±0.5% per 10 mmHg ▵EtCO₂, P<0.01). Analysis was hampered in three patients due to delayed arrival time. Thus, regional hemodynamic impairment was identified with calibrated MRI. Delayed arrival artifacts limited the interpretation of the images in some patients.     

Pre- and Post-Angioplasty Perfusion CT with Acetazolamide Challenge in Patients with Unilateral Cerebrovascular Stenotic Disease

Objective

Perfusion computed tomography (PCT) has the ability to measure quantitative value and produce maps of mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV). We assessed cerebral hemodynamics by using these parameters and acetazolamide (ACZ) challenge for pre- and post-procedural evaluation in patients with unilateral cerebrovascular stenotic disease.

Methods

Thirty patients underwent pre-procedural PCT with ACZ challenge, and 24 patients (80%) was conducted follow up PCT after angioplasty with same protocol. The mean MTT, CBF, and CBV were measured and compared in both middle cerebral arterial (MCA) territories before and after ACZ challenge. Hemispheric ratio and percent change after ACZ challenge were calculated before and after angioplasty.

Results

The mean stenosis rate was 76.6%. Significant increases in MTT (32.6%, p=0.000) and significant decreases in CBF (-14.2%, p=0.000) were found in stenotic side MCA territories. After ACZ challenge, there were significant changes in MTT (37.4%, p=0.000), CBF (-13.1%, p=0.000), and CBV (-10.5%, p=0.001) in pre-procedural perfusion study. However, no significant increases were found in MTT, or decreases in CBF and CBV in post-procedural study. There were no significant changes after ACZ challenge also. In addition, the degrees of these changes (before and after ACZ challenge) were highly correlated with the stenotic degrees in pre-procedural perfusion study.

Conclusion

PCT with ACZ challenge appears to be a useful tool to assess the cerebral perfusion status especially in patients with unilateral symptomatic stenotic disease.     

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 .     

Impaired cerebral vascular and metabolic responses to parametric N-back tasks in subjective cognitive decline

Previous studies reported abnormally increased and/or decreased blood oxygen level-dependent (BOLD) activations during functional tasks in subjective cognitive decline (SCD). The neurophysiological basis underlying these functional aberrations remains debated. This study aims to investigate vascular and metabolic responses and their dependence on cognitive processing loads during functional tasks in SCD. Twenty-one SCD and 18 control subjects performed parametric N-back working-memory tasks during MRI scans. Task-evoked percentage changes (denoted as δ) in cerebral blood volume (δCBV), cerebral blood flow (δCBF), BOLD signal (δBOLD) and cerebral metabolic rate of oxygen (δCMRO₂) were evaluated. In the frontal lobe, trends of decreased δCBV, δCBF and δCMRO₂ and increased δBOLD were observed in SCD compared with control subjects under lower loads, and these trends increased to significant differences under the 3-back load. δCBF was significantly correlated with δCMRO₂ in controls, but not in SCD subjects. As N-back loads increased, the differences between SCD and control subjects in δCBF and δCMRO₂ tended to enlarge. In the parietal lobe, no significant between-group difference was observed. Our findings suggested that impaired vascular and metabolic responses to functional tasks occurred in the frontal lobe of SCD, which contributed to unusual BOLD hyperactivation and was modulated by cognitive processing loads.