Assessing the repeatability of absolute CMRO2, OEF and haemodynamic measurements from calibrated fMRI

Abstract As energy metabolism in the brain is largely oxidative, the measurement of cerebral metabolic rate of oxygen consumption (CMRO 2 ) is a desirable biomarker for quantifying brain activity and tissue viability. Currently, PET techniques based on oxygen isotopes are the gold standard for obtaining whole brain CMRO 2 maps. Among MRI techniques that have been developed as an alternative are dual calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood flow and oxygenation. In this study we quantified the repeatability of a dcFMRI approach developed in our lab, evaluating its limits and informing its application in studies aimed at characterising the metabolic state of human brain tissue over time. Our analysis focussed on the estimates of oxygen extraction fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity (CVR) and CMRO 2 based on a forward model that describes analytically the acquired dual echo GRE signal. Indices of within- and between-session repeatability are calculated from two different datasets both at a bulk grey matter and at a voxel-wise resolution and finally compared with similar indices obtained from previous MRI and PET measurements. Within- and between-session values of intra-subject coefficient of variation (CV intra ) calculated from bulk grey matter estimates 6.7 ± 6.6% (mean ± std.) and 10.5 ± 9.7% for OEF, 6.9 ± 6% and 5.5 ± 4.7% for CBF, 12 ± 9.7% and 12.3 ± 10% for CMRO 2 . Coefficient of variation (CV) and intraclass correlation coefficient (ICC) maps showed the spatial distribution of the repeatability metrics, informing on the feasibility limits of the method. In conclusion, results show an overall consistency of the estimated physiological parameters with literature reports and a satisfactory level of repeatability considering the higher spatial sensitivity compared to other MRI methods, with varied performance depending on the specific parameter under analysis, on the spatial resolution considered and on the study design.