Quantification of brain oxygen extraction and metabolism with [¹⁵O]-gas PET: A technical review in the era of PET/MRI

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO₂) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [¹⁵O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO₂. Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [¹⁵O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO₂ measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [¹⁵O]-oxygen PET for brain physiological assessment.