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The regional differences in cerebral oxygen extraction fraction (OEF) in brain were investigated using positron emission tomography (PET) in detail with consideration of systemic errors in PET measurement estimated by simulation studies. The cerebral blood flow (CBF), cerebral blood volume (CBV), OEF, and cerebral metabolic rate of oxygen (CMRO 2 ) were measured on healthy men by PET with 15 O-labeled gases. The OEF values in the pons and the parahippocampal gyrus were significantly smaller than in the other brain regions. The OEF value in the lateral side of the occipital cortex was largest among the cerebral cortical regions. Simulation studies have revealed that errors in OEF caused by regional differences in the distribution volume of 15 O-labeled water, as well as errors in OEF caused by a mixture of gray and white matter, must be negligible. The regional differences in OEF in brain must exist which might be related to physiological meanings.Article title: Kindly check and confirm the edit made in the article title.I have checked the article title and it is OK as is. Trial registration: The UMIN clinical trial number: UMIN000033382, https://www.umin.ac.jp/ctr/index.htm., (© 2023. The Physiological Society of Japan.)

Purpose: Oxygen extraction fraction (OEF) is a biomarker for the viability of brain tissue in ischemic stroke. However, acquisition of the OEF map using positron emission tomography (PET) with oxygen-15 gas is uncomfortable for patients because of the long fixation time, invasive arterial sampling, and radiation exposure. We aimed to predict the OEF map from magnetic resonance (MR) and PET images using a deep convolutional neural network (CNN) and to demonstrate which PET and MR images are optimal as inputs for the prediction of OEF maps., Methods: Cerebral blood flow at rest (CBF) and during stress (sCBF), cerebral blood volume (CBV) maps acquired from oxygen-15 PET, and routine MR images (T1-, T2-, and T2*-weighted images) for 113 patients with steno-occlusive disease were learned with U-Net. MR and PET images acquired from the other 25 patients were used as test data. We compared the predicted OEF maps and intraclass correlation (ICC) with the real OEF values among combinations of MRI, CBF, CBV, and sCBF., Results: Among the combinations of input images, OEF maps predicted by the model learned with MRI, CBF, CBV, and sCBF maps were the most similar to the real OEF maps (ICC: 0.597 ± 0.082). However, the contrast of predicted OEF maps was lower than that of real OEF maps., Conclusion: These results suggest that the deep CNN learned useful features from CBF, sCBF, CBV, and MR images and predict qualitatively realistic OEF maps. These findings suggest that the deep CNN model can shorten the fixation time for 15 O PET by skipping 15 O 2 scans. Further training with a larger data set is required to predict accurate OEF maps quantitatively., (© 2021. The Author(s).)

The relation between cerebral blood flow (CBF) and cerebral oxygen extraction fraction (OEF) can be expressed using the effective diffusivity for oxygen in the capillary bed (D) as OEF = 1 - exp(-D/CBF). The D value is proportional to the microvessel blood volume. In this study, changes in D during neural activation and deactivation were estimated from changes in capillary and arteriole diameter measured by two-photon microscopy in awake mice. Capillary and arteriole vessel diameter in the somatosensory cortex and cerebellum were measured under neural activation (sensory stimulation) and neural deactivation [crossed cerebellar diaschisis (CCD)], respectively. Percentage changes in D during sensory stimulation and CCD were 10.3 ± 7.3 and -17.5 ± 5.3 % for capillary diameter of <6 μm, respectively. These values were closest to the percentage changes in D calculated from previously reported human positron emission tomography data. This may indicate that thinner capillaries might play the greatest role in oxygen transport from blood to brain tissue.

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with (15)O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C(a)O(2)), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO(2)) 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 CMRO(2) was independent of Hb concentration. Oxygen delivery defined as a product of C(a)O(2) and CBF (C(a)O(2) 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 CMRO(2). The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the (15)O PET data in clinical practice.

Unlabelled: Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET., Methods: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET., Results: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent., Conclusion: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.

The discrepancy between the increases in cerebral blood flow (CBF) and CMRO2 during neural activation causes an increase in venous blood oxygenation and, therefore, a decrease in paramagnetic deoxyhemoglobin concentration in venous blood. This can be detected by functional magnetic resonance imaging (fMRI) as blood oxygenation level-dependent (BOLD) contrast. In the present study, changes in the cerebral oxygen extraction fraction (OEF) that corresponds to the ratio of CMRO2 to CBF, and in the BOLD signal during neural activation, were measured by both positron emission tomography (PET) and fMRI in the same human subjects. C15O, 15O2, and H2(15)O PET studies were performed in each subject at rest (baseline) and during performance of a right-hand motor task. Functional magnetic resonance imaging studies were then performed to measure the BOLD signal under the two conditions. During performance of the motor task, a significant increase in CBF and a significant decrease in OEF were observed in the left precentral gyrus, left superior frontal gyrus, right precentral gyrus, right cingulate gyrus, and right cerebellum. A significant positive correlation was observed between changes in the CBF and the BOLD signal, and a significant negative correlation was observed between changes in the OEF and the BOLD signal. This supports the assumption on which BOLD contrast studies during neural activation are based.

Unlabelled: A method for relative measurement of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) using positron emission tomography (PET) without arterial sampling in patients with hyperacute ischemic stroke was presented., Methods: The method requires two PET scans, one for H2(15)O injection and one for 15O2 inhalation, and calculates regional CBF, CMRO2, and OEF relative to those at the reference brain region by means of table-lookup method. In this study, we calculated "relative lookup-tables" which relate relative CBF to relative H2(15)O count, relative CMRO2 to relative 15O2 count, and relative OEF to relative 15O2/H2(15)O count. Two assumptions were applied to the lookup-table calculation: 1) In the reference region. CBF and OEF were assumed to be 50.0 ml/min/100 ml and 0.40, respectively, 2) Cerebral blood volume (CBV) was assumed to be constant at 4.0 ml/100 ml over the whole brain. Simulation studies were done to estimate the error of the present method derived from the assumptions., Results: For relative CBF measurements, 20% variation in reference CBF gave about +/- 10% error for measured relative CBF at maximum. Changes in CBV caused relatively large errors in measured OEF and CMRO2 when relative CBF and OEF decreased. Errors for measured relative OEF caused by 50% variation in CBV were within +/- 8% at 0.8 of relative CBF and +/- 12% at 0.4 of relative CBF when relative OEF was greater than 1.0., Conclusion: CBV effects caused larger errors in estimated OEF and CMRO2 in the region of the ischemic core with decreasing relative CBF and/or OEF but only slight errors in the region of "misery perfusion" with relative OEF values greater than 1.0. The present method makes PET measurements simpler than with the conventional method and increases understanding of the cerebral circulation and oxygen metabolism in patients with hyperacute stroke of several hours after onset.