Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen

Ito, Hiroshi; Kubo, Hitoshi; Takahashi, Kazuhiro; Nishijima, Ken‐ichi; Ukon, Naoyuki; Nemoto, Ayaka; Sugawara, Shigeyasu; Yamakuni, Ryo; Ibaraki, Masanobu; Ishii, Shiro

doi:10.1007/s12149-021-01578-8

Cited by 5 publications

(6 citation statements)

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“…To the best of our knowledge, we here used multiparametric, quantitative fMRI for the first time to examine the widespread metabolic effects in the human brain during different cognitive states. All quantitative parameter values obtained in this study fell within the range of previously reported data for the healthy human brain, with average values for CBF of 44.5 ± 7.2 ml/100g/min, CBV of 4.8 ± 0.2 %, OEF of 0.39 ± 0.04 [fraction], and CMRO2 of 127.8 ± 18.4 μmol/100g/min in the gray matter (Aoe et al, 2018; Cho et al, 2018; Gauthier & Hoge, 2012; Ito et al, 2021; Lee & Wehrli, 2022; Leontiev & Buxton, 2007; Liang et al, 2013; Raichle et al, 2001; Stone & Blockley, 2017; Wise et al, 2013; J. Zhang et al, 2015, 2015).…”

Section: Discussionsupporting

confidence: 89%

Two distinct modes of hemodynamic responses in the human brain

Epp,

Castrillón,

Yuan

et al. 2023

Preprint

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Functional magnetic resonance imaging (fMRI) detects changes in brain activity by measuring fluctuations in blood oxygenation. While fMRI assumes a fixed relationship between changes in cerebral blood flow (CBF) and metabolic activity, its uniform application across the human cortex lacks complete validation. We used quantitative fMRI together with blood oxygenation level-dependent (BOLD) fMRI to assess oxygen metabolism against both positive and negative BOLD signal changes. We found a surprising mismatch between changes in oxygen consumption and the direction of BOLD signal changes (ΔBOLD) in 14-33% of voxels with significant positive, and in 50-66% of voxels with significant negative ΔBOLD. This implies that a substantial number of voxels with negative ΔBOLD actually demonstrate increased metabolic activity, and vice versa. Contrary to the canonical hemodynamic response model, discordant voxels cover their oxygen demand predominantly via changes in the oxygen extraction fraction (ΔOEF) and not via ΔCBF. This coincides with a higher vascular density and a lower OEF during baseline that we identified in discordant voxels. In summary, we identified a second type of hemodynamic response mechanism for regulating oxygen supply in the human brain. Our results suggest that the classical interpretation of positive and negative BOLD signal changes in terms of increased or decreased neural activity may be too simplistic and we recommend incorporating quantitative MRI or additional CBF measurements for a more accurate assessment of neuronal activity.

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Section: Discussionsupporting

confidence: 89%

Two distinct modes of hemodynamic responses in the human brain

Epp,

Castrillón,

Yuan

et al. 2023

Preprint

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“…The similar regional differences in OEF in the brain were observed between with attenuation corrections by DIXON and DIXONbone. It has been reported that the OEF values that were relative values corresponding to ratios of CMRO 2 to CBF were not affected by the attenuation correction methods, while the CBF, CBV, and CMRO 2 values that included scale factors to radioactivity concentration in the brain might be affected by the attenuation correction methods [ 12 ]. Thus, effects of attenuation correction methods on regional differences in OEF in brain might not be observed.…”

Section: Discussionmentioning

confidence: 99%

“…Nine healthy men (20–27 years) were recruited who were included in the previous study [ 12 ]. No subject had notable organic lesions in the brain according to MRI.…”

Section: Methodsmentioning

confidence: 99%

“…PET measurements with the steady-state method of 15 O-labeled gases, C 15 O, 15 O 2 , and C 15 O 2 were performed on all subjects [ 9 , 21 ]. PET scanning protocol was according to our previous report [ 12 ]. Static PET scanning was started 3 min after 1 min of continuous inhalation of C 15 O gas (a total of approximately 3 GBq supplied by mouth).…”

Section: Methodsmentioning

confidence: 99%

“…Normal values of OEF have been reported to be about 0.4 in cerebral cortical regions [ 8 , 9 ]. There are several reports of normal values of CBF, CBV, OEF, and CMRO 2 [ 8 – 12 ], and regional differences in CBF, CBV, and vascular mean transit time (MTT) have been investigated in detail with analyses of systemic errors in PET measurement [ 13 ]. Regional differences in cerebral vascular response to P a CO 2 changes have also been investigated showing regional differences in cerebral vascular tone in relation with those in MTT [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Oxygen extraction fraction is not uniform in human brain: a positron emission tomography study

Ito,

Ibaraki,

Yamakuni

et al. 2023

J Physiol Sci

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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 (CMRO2) were measured on healthy men by PET with 15O-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 15O-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

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A review of harmonization strategies for quantitative PET

et al. 2023

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PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non-18F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

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Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen

Cited by 5 publications

References 25 publications

Two distinct modes of hemodynamic responses in the human brain

Two distinct modes of hemodynamic responses in the human brain

Oxygen extraction fraction is not uniform in human brain: a positron emission tomography study

A review of harmonization strategies for quantitative PET

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