# A non-invasive, reference region-based method for quantification of cerebral blood flow and oxygen metabolism using oxygen-15 labeled gases and positron emission tomography

**Authors:** Hiroshi Ito, Masanobu Ibaraki, Ryo Yamakuni, Naoyuki Ukon, Shiro Ishii, Kenji Fukushima, Hitoshi Kubo, Kazuhiro Takahashi

PMC · DOI: 10.22038/aojnmb.2025.81433.1578 · 2025-01-01

## TL;DR

This paper introduces a non-invasive PET method to measure brain blood flow and oxygen metabolism without arterial blood sampling.

## Contribution

A novel reference region-based method for quantifying cerebral parameters using PET and oxygen-15 labeled gases without invasive sampling.

## Key findings

- The new method showed good correlation with traditional invasive methods for measuring CBF, CBV, OEF, and CMRO2.
- Simulation studies confirmed minimal errors in the new method under various perfusion conditions.
- The method is valid for investigating cerebrovascular disease pathophysiology.

## Abstract

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 labeled gases is widely used for investigation into the pathophysiology of occlusive cerebrovascular disease. However, all methods for quantification of CBF, CBV, OEF, and CMRO2 by PET with oxygen-15 labeled gases require invasive arterial blood sampling. The present study developed a reference region-based method for quantification of CBF, CBV, OEF, and CMRO2 using PET and oxygen-15 labeled gases based on the steady-state method without invasive arterial blood sampling.

The CBF, CBV, OEF, and CMRO2 were measured in patients with occlusive cerebrovascular disease by PET using 15O-labeled gases, C15O2, C15O, and 15O2, with the steady-state method. In the present method, the ratios of values in a brain region to the reference region for CBF, CBV, OEF, and CMRO2 were calculated without invasive arterial blood sampling.

Good correlations were observed for the ratios of values of the cerebral lesion to the reference brain region for CBF, CBV, OEF, and CMRO2 calculated by the present method as compared with those obtained by the steady-state method with arterial blood sampling, indicating its validity. Simulation studies showed that errors in estimated values calculated by the present method were negligibly small for both conditions of misery perfusion and matched hypoperfusion.

A simple method for noninvasive quantification of CBF, CBV, OEF, and CMRO2 using PET and oxygen-15 labeled gases could be developed based on the steady-state method. This method can be used to investigate the pathophysiology of occlusive cerebrovascular disease.

## Linked entities

- **Chemicals:** oxygen-15 (PubChem CID 25087143)

## Full-text entities

- **Diseases:** occlusive cerebrovascular disease (MESH:D002561), cerebral lesion (MESH:D002539)
- **Chemicals:** 15O (MESH:C000615263), oxygen (MESH:D010100), 15O2 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12205130/full.md

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Source: https://tomesphere.com/paper/PMC12205130