Oxygen extraction fraction brain charts for human lifespan and application for brain disorders

Abstract Cerebral oxygen extraction fraction (OEF) reflects the balance between cerebral oxygen delivery and metabolic demand, but its normative evolution across the human lifespan remains unknown. Here we used rapid, non-contrast TRUST MRI to establish a multisite normative model of global cerebral OEF in 2,025 healthy individuals aged 0-93 years from 17 imaging sites. OEF increased from the neonatal period to middle adulthood, followed by a slower rise and plateau in later life, with the fastest change occurring during early development and no significant sex differences. Individual OEF deviation scores were associated with vascular risk burden in healthy adults. Applying the model to 885 patients revealed disease-related OEF alterations, including positive deviations in pediatric obstructive sleep apnea, autoimmune disorders, brain tumors, mild cognitive impairment and dementia. OEF deviation further tracked tumor grade and Ki-67 proliferation. These findings establish lifespan OEF charting as a scalable framework for individualized physiological neuroimaging.