Breath-hold calibrated fMRI mapping of absolute cerebral metabolic rate of oxygen metabolism (CMRO ): An assessment of the accuracy and repeatability in a healthy adult population.

We previously introduced a calibrated fMRI framework that utilises respiratory modulation with only a single gas (CO) to map the grey matter (GM) cerebral metabolic rate of oxygen consumption (CMRO). The method decouples and estimates the cerebral blood volume (CBV) and the oxygen extraction fraction (OEF) from a single measure of the maximum BOLD modulation. The method links the two parameters of interest with a model of oxygen diffusion from capillaries to mitochondria which incorporates the cerebral blood flow (CBF). Here, we apply this framework to gas-free breath-hold calibrated fMRI (bhc-fMRI), where simultaneous BOLD and ASL acquisitions are combined with modulation of arterial COthrough repeated breath-holding. The accuracy and repeatability of the method is assessed in 33 healthy volunteers at rest and during continuous visual stimulation. Average GM OEF estimated from bhc-fMRI was 0.37 ± 0.04, indicating a small bias of 0.04 (with limits of agreement from -0.11 to 0.12) compared to the whole brain OEF of 0.32 ± 0.07 estimated from sagittal sinus using T2 Relaxation Under Spin Tagging (TRUST). The within-session repeatability of GM estimates were moderate to good for OEF, with ICC = 0.75 (0.56-0.87) and good to excellent for CMRO, with ICC = 0.88 (0.74-0.94). An ROI analysis in the visual cortex found an average CBF increase of 16%, a CMROincrease of 12%, and an OEF decrease of 3% during the visual stimulation. The bhc-fMRI measurement of CMROis simple to implement, has comparable accuracy and repeatability to existing gas-based methods, and is sensitive to modulations in metabolism during functional hyperaemia.