Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO₂), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO₂ and rCBV were determined using C¹⁵O₂, ¹⁵O₂ and C¹⁵O, respectively. rCBF and CMRO₂ were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO₂ was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion. Received: 24 October 1996 Accepted: 30 June 1997     

Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate

Objective  Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) can be estimated from C¹⁵O, H₂ ¹⁵O, and ¹⁵O₂ tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for ¹⁵O₂ gas study for accurate estimation of OEF and CMRO₂. Methods  We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO₂ using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF = 20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO₂ from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBF^g and CBF^w) was 80 and 20, OEF in gray and white matter (E ^g and E ^w) was 0.4 and 0.3, (ii) CBF^g and CBF^w decreased by 50%, and E ^g and E ^w increased by 50% when compared with conditions (i) and (iii). CBF^g and CBF^w decreased by 80%, and E ^g and E ^w increased by 50% when compared with condition (i). Results  The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO₂, 3 min of scan time was desirable. Conclusions  The optimal scan time of ¹⁵O₂ inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO₂.     

Omission of [15O]CO scan for PET CMRO2 examination using 15O-labelled compounds

Objective

CBF, OEF and CMRO₂ provide us important clinical indices and are used for assessing ischemic degree in cerebrovascular disorders. These quantitative images can be measured by PET using ¹⁵O-labelled tracers such as C¹⁵O, C¹⁵O₂ and ¹⁵O₂. To reduce the time of scan, one possibility is to omit the use of CBV data. The present study investigated the influence of fixing the CBV to OEF and CMRO₂ values on subjects with and without cerebrovascular disorders.

Methods

The study consisted of three groups, namely, GROUP-0 (n = 10), GROUP-1 (n = 9), and GROUP-2 (n = 10), corresponding to—without significant disorder, with elevated CBV, and with reduced CBF and elevated OEF, respectively. All subjects received PET examination and using the PET data OEF and CMRO₂ images were computed by fixing CBV and with CBV data. The computed OEF and CMRO₂ values were compared between the methods.

Results

The OEF and CMRO₂ values obtained by fixing the CBV were around 10% underestimation against that with CBV data. The regression analysis showed that these values were comparable (r = 0.93–0.98, P < 0.001). The simulation showed that fixing of the CBV would not derive significant error in either OEF or CMRO₂ values, when changed from 0 to 0.08 ml/g.

Conclusion

This study shows the feasibility of fixing the CBV value for computing OEF and CMRO₂ values in the PET examination, suggesting the CO scan could be eliminated.     

Evaluation of the default-mode network by quantitative <Superscript>15</Superscript>O-PET: comparative study between cerebral blood flow and oxygen consumption

Objective

Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO₂). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative ¹⁵O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO₂ to the DMN.

Methods

Nine healthy volunteers (5 men and 4 women; mean age, 47.0?±?1.2 years) were studied by means of ¹⁵O-O₂, ¹⁵O-CO gases and ¹⁵O-water PET. Quantitative CBF and CMRO₂ images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson’s correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO₂, respectively. We defined r?>?0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO₂.

Results

Significant positive correlations (r?>?0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO₂. Among them, 12 overlapping networks were observed between CBF and CMRO₂. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO₂, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity.

Conclusions

We estimated the functional correlations in the DMN by means of quantitative PET using ¹⁵O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO₂, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

     

Regional cerebral blood flow and oxygen metabolism in a patient with Korsakoff syndrome

We report a functional neuroimaging study of a patient clinically diagnosed with Korsakoff syndrome. Positron emission tomography (PET) with the¹⁵O inhalation method showed decreased regional cerebral blood flow (rCBF) and decreased regional cerebral metabolic ratio for oxygen (rCMRO₂) in the bilateral fronto-temporal areas and in the left thalamus. These results suggest that dysfunction of the frontal-thalamic neural network plays a role in the disturbance of Korsakoff syndrome.     

Influence of residual oxygen-15-labeled carbon monoxide radioactivity on cerebral blood flow and oxygen extraction fraction in a dual-tracer autoradiographic method

Objective  Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with ¹⁵O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating ¹⁵O₂ and C¹⁵O₂ gases. In this protocol, before the sequential PET scan with ¹⁵O₂ and C¹⁵O₂ gases (¹⁵O₂–C¹⁵O₂ PET scan), a PET scan with C¹⁵O should be preceded to obtain CBV image. C¹⁵O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C¹⁵O might exist during a ¹⁵O₂–C¹⁵O₂ PET scan. As the current DARG method assumes no residual C¹⁵O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C¹⁵O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C¹⁵O radioactivity. Methods  In the simulation, normal and ischemic conditions were considered. The ¹⁵O₂ and C¹⁵O₂ PET count curves with the residual C¹⁵O PET counts were generated by the arterial input function with the residual C¹⁵O radioactivity. The amounts of residual C¹⁵O radioactivity were varied by changing the interval between the C¹⁵O PET scan and ¹⁵O₂–C¹⁵O₂ PET scan, and the absolute inhaled radioactivity of the C¹⁵O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C¹⁵O gas in the input function and PET counts. Results  Our simulations revealed that the CBF and OEF values were underestimated by the residual C¹⁵O radioactivity. The magnitude of this underestimation depended on the amount of C¹⁵O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. Conclusions  This study showed the influence of C¹⁵O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C¹⁵O, and the physiological condition.     

Cortical Cerebral Blood Flow,Oxygen Extraction Fraction,and Metabolic Rate in Patients with Middle Cerebral Artery Stenosis or Acute Stroke

BACKGROUND AND PURPOSE:With the advances of magnetic resonance technology, the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen can be measured in MRI. Our aim was to measure the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen use in patients with different severities of middle cerebral artery stenosis or acute stroke by using the arterial spin-labeling and susceptibility-weighted imaging techniques.MATERIALS AND METHODS:Fifty-seven patients with MCA stenosis or acute stroke were recruited and classified into 4 groups: mild MCA stenosis (group 1), severe MCA stenosis (group 2), occluded MCA (group 3), and acute stroke (group 4). Arterial spin-labeling and SWI sequences were used to acquire CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen.RESULTS:The oxygen extraction fraction in hemispheres with mild MCA stenosis (group 1) was remarkably higher than that in the contralateral hemisphere. In addition, hemispheres with severe MCA stenosis (group 2) had significantly lower CBF and a significantly higher oxygen extraction fraction than the contralateral hemisphere. Hemispheres with occluded MCA (group 3) or acute stroke (group 4) had a significantly lower CBF and cerebral metabolic rate of oxygen and a significantly higher oxygen extraction fraction than the contralateral hemisphere.CONCLUSIONS:The oxygen extraction fraction gradually increased in groups 1–3. When this offset a decrease in CBF, the cerebral metabolic rate of oxygen remained at a normal level. An occluded MCA led to reduction in both the CBF and cerebral metabolic rate of oxygen. Moreover, the oxygen extraction fraction and cerebral metabolic rate of oxygen significantly increased and decreased, respectively, in the occluded MCA region during acute stroke.

A reduction in cerebral blood flow in brain tissue is typically accompanied by a compensatory increase in the oxygen extraction fraction (OEF) to maintain normal neuronal function.¹ However, the risk of stroke is greatly increased once the maximum OEF is achieved.² The presence of increased OEF in stroke is an independent predictor of subsequent stroke in patients.^3,4 Consequently, both CBF and OEF are important indicators for stroke; however, neither parameter sufficiently predicts the risk of this condition. It is possible to use both parameters and the arterial oxygen content to derive cerebral metabolic rate of oxygen (CMRO₂) use, which is of critical importance in the occurrence of stroke.¹Positron-emission tomography provides the most accurate in vivo OEF and CMRO₂ measurements; however, it is expensive and requires administration of radioactive isotopes. Both OEF and CBF can be determined using MR susceptometry and arterial spin-labeling (ASL).^5,6 MR susceptometry uses gradient-echo phase maps to estimate oxygen saturation in segments of the jugular and gray matter veins.^7,8 This technique requires blood vessels to have a substantially greater length than the diameter.^7,8 Susceptibility-weighted imaging is a type of MR susceptometry that can obtain measurements of venous oxygen saturation by using the phase difference between the venous blood and surrounding tissue.^9,10 ASL is a noninvasive technique that can measure CBF.^11,12 The gray matter CMRO₂ can be obtained from local CBF and OEF measurements.Most previous PET studies have focused on OEF and CMRO₂ in patients with an occluded carotid artery; few studies have investigated the stenotic or occluded middle cerebral artery.^13,14 To the best of our knowledge, no studies have assessed CBF, OEF, and CMRO₂ relative to the degree of MCA stenosis. To address this question, we measured CBF, OEF, and CMRO₂ in patients with different degrees of MCA stenosis or stroke via ASL and susceptibility-weighted phase imaging.     

Quantification of regional cerebral blood flow in rats using an arteriovenous shunt and micro-PET

IntroductionMeasurement of regional cerebral blood flow (rCBF) in rodents can provide knowledge of pathophysiology of the cerebral circulation, but generally requires blood sampling for analysis during positron emission tomography (PET). We therefore tested the feasibility of using an arteriovenous (AV) shunt in rats for less invasive blood analysis.MethodsSix anesthetized rats received [¹⁵O]H₂O and [¹⁵O]CO PET scans with their femoral artery and vein connected by an AV shunt, the activity within which was measured with a germanium ortho-oxysilicate scintillation detector. The [¹⁵O]H₂O was intravenously injected either at a faster or slower injection rate, while animals were placed either with their head or heart centered in the gantry. The time–activity curve (TAC) from the AV shunt was compared with that from the cardiac ventricle in PET image. The rCBF values were calculated by a nonlinear least-square method using the dispersion-corrected AV-shunt TAC as an input.ResultsThe AV-shunt TAC had higher signal-to-noise ratio, but also had delay and dispersion compared with the image-derived TAC. The delay time between the AV-shunt TAC and image-based TAC ranged from 11 to 21 s, while the dispersion was estimated to be ～5 s as a time constant of the dispersion model of exponential function, and both were properly corrected. In a steady-state condition of [¹⁵O]CO PET, the blood activity concentration by AV-shunt TAC was also comparable in height with the image-based TAC corrected for partial volume. Whole-brain CBF values measured by [¹⁵O]H₂O were 0.37±0.04 (mean±S.D.) ml/g/min, partition coefficient was 0.73±0.04 ml/g, and the CBF varied in a linear relationship with partial pressure of carbon dioxide during each scan.ConclusionsThe AV-shunt technique allows less invasive, quantitative and reproducible measurement of rCBF in [¹⁵O]H₂O PET studies in rats than direct blood sampling and radioassay.     

QUantitative Imaging of eXtraction of oxygen and TIssue consumption (QUIXOTIC) using venular‐targeted velocity‐selective spin labeling

While oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) are fundamental parameters of brain health and function, a robust MRI‐based mapping of OEF and CMRO₂ amenable to functional MRI (fMRI) has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity‐selective spin labeling to isolate MR signal exclusively from postcapillary venular blood on a voxel‐by‐voxel basis. Measuring the T₂ of this venular‐targeted blood allows calibration to venular oxygen saturation (Y_v) via theoretical and experimental T₂ versus blood oxygen saturation relationships. Y_v is converted to OEF, and baseline CMRO₂ is subsequently estimated from OEF and additional cerebral blood flow and hematocrit measurements. Theory behind the QUIXOTIC technique is presented, and implications of cutoff velocity (V_CUTOFF) and outflow time parameters are discussed. Cortical gray matter values obtained with QUIXOTIC in 10 healthy volunteers are Y_v = 0.73 ± 0.02, OEF = 0.26 ± 0.02, and CMRO₂ = 125 ± 15 μmol/100 g min. Results are compared to global measures obtained with the T₂ relaxation under spin tagging (TRUST) technique. The preliminary data presented suggest that QUIXOTIC will be useful for mapping Y_v, OEF, and CMRO₂, in both clinical and functional MRI settings. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Automatic labeling method for injectable 15O-oxygen using hemoglobin-containing liposome vesicles and its application for measurement of brain oxygen consumption by PET

IntroductionThe aim of this study was to develop an injectable ¹⁵O-O₂ system using hemoglobin-containing vesicles (HbV), a type of artificial red blood cell, and to investigate the feasibility of ¹⁵O₂-labeled HbV (¹⁵O₂-HbV) to measure cerebral metabolic rate of oxygen (CMRO₂) in rats.MethodsThe direct bubbling method was combined with vortexing to enhance labeling efficiency of HbV with ¹⁵O-O₂ gas. l-Cysteine was added as a reductant to protect hemoglobin molecules in HbV from oxidation at different concentrations, and labeling efficiencies were also compared. Measurement of cerebral blood flow (CBF) and CMRO₂ in five normal rats was performed using a small animal PET scanner after the injection of H₂¹⁵O and ¹⁵O₂-HbV to evaluate the precision of hemodynamic parameters quantitatively.ResultsThe labeling efficiency of HbV was significantly increased when vortexing and bubbling were combined compared with the simple bubbling method (P<.05). The most efficient method for labeling was bubbling of ¹⁵O-O₂ combined with vortexing and the addition of 2.8 mM l-cysteine in HbV solution. The mean radioactivity of 214.4±7.8 MBq/mL HbV was obtained using this method. PET scans using ¹⁵O₂-HbV and H₂¹⁵O yielded a mean CMRO₂ value of 6.8±1.4 (mL/min per 100 g) in rats with normal CBF of 51.4±7.9 (mL/min per 100 g).ConclusionAddition of l-cysteine to HbV and simple direct bubbling of ¹⁵O-O₂ gas combined with vortexing was the most efficient method for preparation of ¹⁵O₂-HbV. The present injectable system using ¹⁵O₂-HbV was successfully utilized to measure CMRO₂ in rats, indicating that this new method could be useful for animal models to measure oxygen metabolism in the brain.     

Impact of subject head motion on quantitative brain 15O PET and its correction by image-based registration algorithm

Objective

Subject head motion during sequential ¹⁵O positron emission tomography (PET) scans can result in artifacts in cerebral blood flow (CBF) and oxygen metabolism maps. However, to our knowledge, there are no systematic studies examining this issue. Herein, we investigated the effect of head motion on quantification of CBF and oxygen metabolism, and proposed an image-based motion correction method dedicated to ¹⁵O PET study, correcting for transmission–emission mismatch and inter-scan mismatch of emission scans.

Methods

We analyzed ¹⁵O PET data for patients with major arterial steno-occlusive disease (n = 130) to determine the occurrence frequency of head motion during ¹⁵O PET examination. Image-based motion correction without and with realignment between transmission and emission scans, termed simple and 2-step method, respectively, was applied to the cases that showed severe inter-scan motion.

Results

Severe inter-scan motion (>3 mm translation or >5° rotation) was observed in 27 of 520 adjacent scan pairs (5.2 %). In these cases, unrealistic values of oxygen extraction fraction (OEF) or cerebrovascular reactivity (CVR) were observed without motion correction. Motion correction eliminated these artifacts. The volume-of-interest (VOI) analysis demonstrated that the motion correction changed the OEF on the middle cerebral artery territory by 17.3 % at maximum. The inter-scan motion also affected CBV, CMRO₂ and CBF, which were improved by the motion correction. A difference of VOI values between the simple and 2-step method was also observed.

Conclusions

These data suggest that image-based motion correction is useful for accurate measurement of CBF and oxygen metabolism by ¹⁵O PET.     

Can the detection of misery perfusion in chronic cerebrovascular disease be based on reductions in baseline CBF and vasoreactivity?

Purpose: The aim of this study was to clarify whether decreases in baseline regional cerebral blood flow (rCBF) and in residual cerebral vasoreactivity (CVR), assessed by the acetazolamide (ACZ) challenge, can detect misery perfusion in patients with chronic cerebrovascular disease (CVD). Methods: Oxygen extraction fraction (OEF) and other haemodynamic parameters were measured in 115 patients (64±9 years old) with unilateral cerebrovascular steno-occlusive disease (>70% stenosis) using ¹⁵O-gas and water PET. A significant elevation of OEF, by greater than the mean+2SD compared with healthy controls, was defined as misery perfusion. CBF, CVR determined by percent change in CBF after ACZ administration, OEF and other haemodynamic parameters in the territories of the bilateral middle cerebral arteries were analysed. Diagnostic accuracy for the detection of misery perfusion using the criteria determined by baseline CBF and CVR was evaluated in all patients and in only those patients with occlusive lesions. Results: Ten of 24 patients with misery perfusion showed a significant reduction in CVR. Using criteria determined by significant decreases in CVR and baseline CBF, misery perfusion was detected with a sensitivity of 42% and a specificity of 95% in all patients. In patients with occlusive lesions (n=50), sensitivity was higher but specificity was slightly lower. The diagnostic accuracy of the threshold determined by baseline CBF alone was similar in all patients and in only those patients with occlusive lesions, and was higher than that achieved using the asymmetry index of OEF. Conclusion: Reductions in CVR and baseline CBF in the ACZ challenge for CVD would detect misery perfusion with high specificity. Reduction in baseline rCBF is more accurate than reduction in CVR alone for the detection of misery perfusion.     

Test–retest reproducibility of a rapid method to measure brain oxygen metabolism

Cerebral metabolic rate of oxygen (CMRO₂) is an important index of tissue viability and brain function, but this parameter cannot yet be measured routinely on clinical scanners. Recently, a noninvasive technique was proposed which estimates global CMRO₂ by concomitantly measuring oxygen‐extraction‐fraction using T₂‐relaxation‐under‐spin‐tagging MRI and pulse oximetry, and cerebral‐blood‐flow using phase‐contrast MRI. This study sought to establish a standard acquisition procedure for this technique and to evaluate its test–retest reproducibility in healthy subjects. Each subject was examined in five sessions and each session included two measurements. Intrasession, intersession, and intersubject coefficients of variation for CMRO₂ were found to be 3.84 ± 1.44% (N = 7, mean ± standard deviation), 6.59 ± 1.56%, and 8.80% respectively. These reproducibility values were comparable or slightly superior to ¹⁵O positron emission tomography (PET) results reported in the literature. It was also found that oxygen‐extraction‐fraction and cerebral‐blood‐flow tended to co‐vary across sessions (P = 0.002) and subjects (P = 0.01), and their coefficients of variation were greater than that of CMRO₂. The simplicity and reliability features may afford this global CMRO₂ technique great potential for immediate clinical applications. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Use of 123I-IMP brain SPET to predict outcome following STA-MCA bypass surgery: cerebral blood flow but not vasoreactivity is a predictive parameter

Superficial temporal artery – middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine (¹²³I-IMP) brain single-photon emission tomography (SPET). ¹²³I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide challenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide – rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5±19.3 years) into group I, who had a change in their resting CBF from before to after surgery of >10%, and 16 patients (54.0±18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ≤10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P<0.05). Resting CBF improved by 20.4%±7.5% in group I and by 0.9%±6.9% in group II patients after surgery (P<0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6%±17.7%) and group II patients (24.6%±15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59±0.09 before surgery to 0.46±0.06 after surgery (P<0.05), while patients in the group II PET subset showed no statistical difference in OEF before surgery (0.58±0.14) and after surgery (0.54± 0.05). We conclude that the outcome of STA-MCA bypass surgery can be predicted by the improvement in resting CBF but not by the improvement in vasoreactivity. Received 1 May and in revised form 3 August 1998     

Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease

Objective

Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease.

Methods

We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and ¹⁵O-labeled gases. The functional values in the cortex–subcortex, basal ganglia, and centrum semiovale were compared between the two groups.

Results

Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1–91.5 mL vs. median: 11.3; range: 4.2–73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO₂ between the two groups.

Conclusions

Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.

     

Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters

Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labelled (R)nicotine. The rCBF of the same subjects was measured by PET using the C¹⁵O₂ inhalation steady-state method. The distribution of¹¹C activity in the brain after injection of¹¹C-(R)nicotine was almost equivalent to the CBF image obtained with the C¹⁵O₂ inhalation stead-state method. The kinetics of¹¹C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with¹¹C-(R)nicotine were higher than with C¹⁵O₂ gas. The relatively long fixed distribution of¹¹C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H₂ ¹⁵O.     

Differences in vasodilatory capacity and changes in cerebral blood flow induced by acetazolamide in patients with cerebrovascular disease.

To investigate changes in cerebral blood flow (CBF) and blood volume induced by acetazolamide (ACZ) in patients with a variable autoregulatory status responding to reduced perfusion pressure, PET measurements of hemodynamic parameters were performed on patients with cerebrovascular disease, and the relationships between the parameters were evaluated. METHODS: Sixteen patients with unilateral major cerebral arterial occlusive disease underwent PET studies with (15)O-gas and the steady-state method to obtain hemodynamic parameters in the brain. All patients and 8 healthy volunteers underwent H(2)(15)O PET at baseline and 10 min after ACZ injection to calculate the CBF and arterial-to-capillary blood volume (V(0)) based on a 2-compartment model. RESULTS: The regional CBF (rCBF) and V(0) increased significantly after ACZ administration in volunteers and in the hemisphere contralateral to the ischemic side in patients. However, in a subgroup of patients with disease who showed a significant reduction in the rCBF increase in the ipsilateral hemisphere, the ACZ challenge caused a decrease in the rCBF even though the V(0) showed a significant increase. The reduction in the rCBF increase was associated with an asymmetric increase in oxygen extraction fraction (OEF) but not with an absolute OEF increase. CONCLUSION: The increases in rCBF and V(0) induced by ACZ administration, as well as absolute OEF value in the baseline condition, did not necessarily parallel each other in the ipsilateral hemispheres of patients. Thus, the increase in rCBF after ACZ challenge may not represent vasodilatory capacity in patients with cerebrovascular disease, especially in the regions with a reduced rCBF response.     

Effect of carotid artery stenting on cerebral blood flow: evaluation of hemodynamic changes using arterial spin labeling

Introduction

The purpose of this work was to quantitatively evaluate the hemodynamic changes after carotid artery stenting (CAS) by measuring cerebral blood flow (CBF) using arterial spin labeling (ASL).

Methods

Twenty sets of pre- and postprocedural CBF maps were acquired using ASL in patients who underwent CAS. Vascular territory- and anatomical structure-based regions of interest were applied to the CBF maps. Relative CBF (rCBF) was calculated by adjusting ipsilateral CBF with contralateral CBF. To assess the changes in rCBF after CAS (ΔrCBF), we calculated the following difference: $ \Delta\mathrm{rCBF}=\mathrm{rCB}{{\mathrm{F}}_{\mathrm{postprocedural}}}-\mathrm{rCB}{{\mathrm{F}}_{\mathrm{preprocedural}}} $ .

Results

Postprocedural CBFs were significantly higher than preprocedural CBFs for internal carotid artery and middle cerebral artery territories (P?<?0.05 in both). Postprocedural rCBFs were also significantly higher than preprocedural rCBFs for internal carotid artery and middle cerebral artery territories (P?<?0.05 in both). Significant correlations were observed between preprocedural rCBF and ΔrCBF for the internal carotid artery and middle cerebral artery territories (r?=??0.7211, P?=?0.0003 and r?=??0.6427, P?=?0.0022, respectively). Areas in which the ΔrCBF values were >5.00 ml?100 g^?1 min^?1 were the precentral, postcentral, middle frontal, middle temporal (caudal), superior parietal, and angular gyri.

Conclusions

ASL has potential as a noninvasive imaging tool for the quantitative evaluation of hemodynamic changes after CAS. CAS improves cerebral perfusion in patients with carotid artery stenosis, and patients with greater perfusion deficits prior to CAS have greater improvement in perfusion after CAS. In addition, eloquent areas show the greatest improvement in perfusion.     

Clinical significance of reduced cerebral metabolism in multiple sclerosis: A combined PET and MRI study

Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease’s natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO₂). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman’s rank correlation coefficients. A general reduction in rCBF and rCMRO₂ in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO₂. A correlation between the decrease in rCMRO₂ and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information.