Oxygen Extraction Fraction at Maximally Vasodilated Tissue in the Ischemic Brain Estimated from the Regional CO2 Responsiveness Measured by Positron Emission Tomography

The oxygen extraction fraction (OEF) at maximally vasodilated tissue in patients with chronic cerebrovascular disease was evaluated using positron emission tomography. The vascular responsiveness to changes in PaCO2 was measured by the H215O autoradiographic method. It was correlated with the resting-state OEF, as estimated using the 15O steady-state method. The subjects comprised 15 patients with unilateral or bilateral occlusion and stenosis of the internal carotid artery or middle cerebral artery or moyamoya disease. In hypercapnia, the scattergram between the OEF and the vascular responsiveness to changes in PaCO2 revealed a significant negative correlation in 11 of 19 studies on these patients, and the OEF at the zero cross point of the regression line with a vascular responsiveness of 0 was 0.53 ± 0.08 (n = 11). This OEF in the resting state corresponds to exhaustion of the capacity for vasodilation. The vasodilatory capacity is discussed in relation to the lower limit of autoregulation.

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Validation of T 2 ‐based oxygen extraction fraction measurement with 15 O positron emission tomography

Magnetic Resonance in Medicine ◽

10.1002/mrm.28410 ◽

2020 ◽

Vol 85 (1) ◽

pp. 290-297

Author(s):

Dengrong Jiang ◽

Shengwen Deng ◽

Crystal G. Franklin ◽

Michael O'Boyle ◽

Wei Zhang ◽

...

Keyword(s):

Positron Emission Tomography ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Oxygen Extraction ◽

Extraction Fraction ◽

Positron Emission ◽

Fraction Measurement

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Measurement of End-Capillary Po2 with Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.76 ◽

1988 ◽

Vol 8 (3) ◽

pp. 403-410 ◽

Cited By ~ 6

Author(s):

N. M. Alpert ◽

R. B. Buxton ◽

J. A. Correia ◽

R. M. Katz ◽

R. H. Ackerman

Keyword(s):

Positron Emission Tomography ◽

Oxygen Saturation ◽

Normal Subjects ◽

Oxygen Metabolism ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Oxygen Extraction ◽

Protein Levels ◽

Extraction Fraction ◽

Positron Emission

The analysis of positron emission tomography measurements of oxygen metabolism has been extended to provide a quantitative estimate of end-capillary Po2. The principle of this extension rests on the idea that the oxygen extraction fraction can be used to calculate the end-capillary oxygen saturation of the blood. The relation between oxygen saturation and Po2 is obtained through the oxygen dissociation curve. Our studies show that in addition to the local oxygen extraction fraction, arterial Po2 and pH values are needed in the calculation, whereas fairly large variations in factors such as Pco2, hematocrit, hemoglobin, and plasma protein levels have little or no effect. Rough estimates of end-capillary Po2 can be made using standard o2 dissociation nomograms. Blood gas and acid-base properties of blood have been known for decades, making it possible to account accurately for individual differences that may be encountered when studying patients. Measurements in nine normal subjects yielded a mean end-capillary Po2 value of 31.2 mm Hg. The ability to make a quantitative visualization of altered patterns of end-capillary Po2 provides an additional dimension to the investigation of stroke disease and tumor metabolism.

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Oxygen extraction fraction measurement using quantitative susceptibility mapping: Comparison with positron emission tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15606713 ◽

2015 ◽

Vol 36 (8) ◽

pp. 1424-1433 ◽

Cited By ~ 37

Author(s):

Kohsuke Kudo ◽

Tian Liu ◽

Toshiyuki Murakami ◽

Jonathan Goodwin ◽

Ikuko Uwano ◽

...

Keyword(s):

Positron Emission Tomography ◽

Normal Subjects ◽

Susceptibility Mapping ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Oxygen Extraction ◽

Inversion Method ◽

Quantitative Susceptibility Mapping ◽

Extraction Fraction ◽

Positron Emission

The purposes of this study are to establish oxygen extraction fraction (OEF) measurements using quantitative susceptibility mapping (QSM) of magnetic resonance imaging (MRI), and to compare QSM–OEF data with the gold standard 15O positron emission tomography (PET). Twenty-six patients with chronic unilateral internal carotid artery or middle cerebral artery stenosis or occlusion, and 15 normal subjects were included. MRI scans were conducted using a 3.0 Tesla scanner with a three-dimensional spoiled gradient recalled sequence. QSM images were created using the morphology-enabled dipole inversion method, and OEF maps were generated from QSM images using extraction of venous susceptibility induced by deoxygenated hemoglobin. Significant correlation of relative OEF ratio to contra-lateral hemisphere between QSM–OEF and PET–OEF was observed (r = 0.62, p < 0.001). The local (intra-section) correlation was also significant (r = 0.52, p < 0.001) in patients with increased PET–OEF. The sensitivity and specificity of OEF increase in QSM was 0.63 (5/8) and 0.89 (16/18), respectively, in comparison with PET. In conclusion, good correlation was achieved between QSM–OEF and PET–OEF in the identification of elevated OEF in affected hemispheres of patients with unilateral chronic steno-occlusive disease.

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Model Dependency and Estimation Reliability in Measurement of Cerebral Oxygen Utilization Rate with Oxygen-15 and Dynamic Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1986.13 ◽

1986 ◽

Vol 6 (1) ◽

pp. 105-119 ◽

Cited By ~ 50

Author(s):

Sung-Cheng Huang ◽

DaGan Feng ◽

Michael E. Phelps

Keyword(s):

Positron Emission Tomography ◽

Blood Flow ◽

Low Noise ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Vascular Volume ◽

Dynamic Positron Emission Tomography ◽

Extraction Fraction ◽

Positron Emission ◽

Model Configuration

The use of oxygen-15 and dynamic positron emission tomography (PET) for the measurement of CMRO was investigated in terms of the achievable accuracy of CMRO and its sensitivity to model configuration assumed in the estimation. Three models of different descriptions for the vascular radioactivity in tissue were examined by computer simulation. By simulating the tracer kinetics with one model and curve fitting them with another, it was found that the CMRO measurement was very sensitive to the model configuration used and it needed kinetic data of low noise level to determine the correct model to use. The approach of sensitivity functions and covariance matrices was used to examine the estimation reliability and error propagation of the model parameters. It was found that for all three model configurations examined the reliability of the CMRO estimate was dependent on the blood flow and oxygen extraction fraction in tissue (∼2% in tissues of high blood flow and normal extraction and 10% in tissues of low blood flow and low extraction fraction, in a study of 1 × 106 counts/brain slice in 3 min). The estimation reliability is drastically decreased if the total data collection time is reduced to 1 min but is not critically sensitive to the scan sampling interval used. Estimating blood flow or vascular volume simultaneously with CMRO will reduce the reliability of the CMRO estimate by ∼50%. Propagation of parameter error from blood flow or vascular volume to CMRO is dependent on the model configuration as well as the scanning schedule and estimation procedure used. Results from the study provide useful information for improving the study procedure of CMRO measurements. The present study also illustrates a general representation of PET measurements and an approach that can be applied to other tracer techniques in PET for selecting appropriate model configurations and for designing proper experimental procedures.

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Relationships between High Oxygen Extraction Fraction in the Acute Stage and Final Infarction in Reversible Middle Cerebral Artery Occlusion: An Investigation in Anesthetized Baboons with Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199611000-00012 ◽

1996 ◽

Vol 16 (6) ◽

pp. 1176-1188 ◽

Cited By ~ 66

Author(s):

Alan R. Young ◽

Giuliano Sette ◽

Omar Touzani ◽

Patrice Rioux ◽

Jean Michel Derlon ◽

...

Keyword(s):

Positron Emission Tomography ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Artery Occlusion ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Ischemic Damage ◽

Extraction Fraction ◽

Positron Emission ◽

Cerebral Artery Occlusion

Studies in humans suggest that regions that show maximal increases in brain oxygen extraction fraction (OEF) in the hours following an ischemic episode are those most vulnerable for infarction and are often, although not always, associated with the final site of infarction. To clarify this issue, we followed the hemodynamic and metabolic characteristics of regions with an initially maximally increased OEF and compared them with the ultimately infarcted region in an experimental stroke model. Positron emission tomography (PET) was used to obtain functional images of the brain prior to and following reversible unilateral middle cerebral artery occlusion (MCAO) in 11 anesthetized baboons. To model early reperfusion, the clips were removed 6 h after occlusion. Successive measurements of regional CBF (rCBF), regional CMRO2 (rCMRO2), regional cerebral blood volume, and regional OEF (rOEF) were performed during the acute (up to 2 days) and chronic (>15 days) stage. Late magnetic resonance imaging (MRI) scans (coregistered with PET) were obtained to identify infarction. Reversible MCAO produced an MRI-measurable infarction in 6 of 11 baboons; the others had no evidence of ischemic damage. Histological analysis confirmed the results of the MRI investigation but failed to show any evidence of cortical ischemic damage. The lesion was restricted to the head of the caudate nucleus, internal capsule, and putamen. The infarct volume obtained was 0.58 ± 0.31 cm3. The infarcts were situated in the deep MCA territory, while the area of initially maximally increased OEF was within the cortical mantle. The mean absolute rCBF value in the infarct region of interest (ROI) was not significantly lower than in the highest-OEF ROI until 1–2 days post-MCAO. Cerebral metabolism in the deep MCA territory was always significantly lower than that of the cortical mantle; decreases in CMRO2 in the former region were evident as early as 1 h post-MCAO. In the cortical mantle, the rOEF was initially significantly higher than in the infarct-to-be zone. Subsequently, the OEF declined in both regions. The differences in the time course of changes in CMRO2 and OEF between these two regions, with the eventually infarcted area showing earlier metabolic degradation and in turn decline in OEF, presumably underlie their different final outcomes. In conclusion, following MCAO, the region that shows an early maximal increase in the OEF is both topographically and physiologically distinct from the region with final consolidated infarction if reperfusion is allowed at 6 h. This high OEF, although indicative of a threatened condition, is not an indicator of inescapable consolidated infarction and is thus a situation in which therapy could be envisaged. Whether or not it is at risk of infarction and thus constitutes one target for therapy remains to be seen.

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Failure of Cerebral Hemodynamic Selection in General or of Specific Positron Emission Tomography Methodology?

Stroke ◽

10.1161/strokeaha.111.627745 ◽

2011 ◽

Vol 42 (12) ◽

pp. 3637-3639 ◽

Cited By ~ 36

Author(s):

Andrew P. Carlson ◽

Howard Yonas ◽

Yue-Fang Chang ◽

Edwin M. Nemoto

Keyword(s):

Positron Emission Tomography ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Ratio Method ◽

Hemodynamic Compromise ◽

Extraction Fraction ◽

Positron Emission ◽

Risk Patients ◽

Early Closure ◽

Selection For

Background and Purpose— The Carotid Occlusion Surgery Study (COSS) was an improvement over the Extracranial–Intracranial Bypass Study, which did not utilize physiological selection. To assess possible reasons for early closure of the COSS trial, we reviewed COSS methods used to identify high-risk patients and compared results with separate quantitative data. Methods— Increased oxygen extraction fraction (OEF) by positron emission tomography is a gold standard for ischemia, but the specific thresholds and equivalency of the semiquantitative OEF ratio utilized in COSS and quantitative OEF are at issue. Results— The semiquantitative hemispheric OEF ratio used in COSS did not identify the same group of patients as did quantitative OEF using a threshold of 50%. Conclusions— The failure of COSS is likely caused by a failure of the semiquantitative, hemispheric OEF ratio method rather than by the selection for bypass based on hemodynamic compromise.

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Effects of Sevoflurane, Propofol, and Adjunct Nitrous Oxide on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans

Anesthesiology ◽

10.1097/00000542-200309000-00015 ◽

2003 ◽

Vol 99 (3) ◽

pp. 603-613 ◽

Cited By ~ 250

Author(s):

Kaike K. Kaisti ◽

Jaakko W. Långsjö ◽

Sargo Aalto ◽

Vesa Oikonen ◽

Hannu Sipilä ◽

...

Keyword(s):

Positron Emission Tomography ◽

Blood Flow ◽

Nitrous Oxide ◽

Regional Cerebral Blood Flow ◽

Emission Tomography ◽

Oxygen Extraction Fraction ◽

Regional Cerebral Blood ◽

Extraction Fraction ◽

Positron Emission ◽

End Tidal

Background Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography. Methods 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level. Results The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 microg/ml during propofol alone and 3.5 +/- 0.7 microg/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone. Conclusions Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.

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