Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen consumption and effective oxygen diffusivity

&NA; Dual‐calibrated fMRI is a multi‐parametric technique that allows for the quantification of the resting oxygen extraction fraction (OEF), the absolute rate of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes during hypercapnic and hyperoxic gas challenges. Here we propose an extension to this methodology that permits the simultaneous quantification of the effective oxygen diffusivity of the capillary network (DC). The effective oxygen diffusivity has the scope to be an informative biomarker and useful adjunct to CMRO2, potentially providing a non‐invasive metric of microvascular health, which is known to be disturbed in a range of neurological diseases. We demonstrate the new method in a cohort of healthy volunteers (n = 19) both at rest and during visual stimulation. The effective oxygen diffusivity was found to be highly correlated with CMRO2 during rest and activation, consistent with previous PET observations of a strong correlation between metabolic oxygen demand and effective diffusivity. The increase in effective diffusivity during functional activation was found to be consistent with previously reported increases in capillary blood volume, supporting the notion that measured oxygen diffusivity is sensitive to microvascular physiology. HighlightsWe propose a new framework for the analysis of calibrated fMRI to map CMRO2 and oxygen diffusivity in the brain.The framework is examined with modelling studies and in‐vivo at rest and during visual stimulation.Oxygen diffusivity is found to be highly correlated with CMRO2, evidence of a tight structural‐functional relationship.