Regional Reproducibility of BOLD Calibration Parameter M, OEF and Resting-State CMRO(2) Measurements with QUO2 MRI

The current generation of calibrated MRI methods goes beyond simple localization of task-related responses to allow the mapping of resting-state cerebral metabolic rate of oxygen (CMRO(2)) in micromolar units and estimation of oxygen extraction fraction (OEF). Prior to the adoption of such techniques in neuroscience research applications, knowledge about the precision and accuracy of absolute estimates of CMRO(2) and OEF is crucial and remains unexplored to this day. In this study, we addressed the question of methodological precision by assessing the regional inter-subject variance and intra-subject reproducibility of the BOLD calibration parameter M, OEF, O(2) delivery and absolute CMRO(2) estimates derived from a state-of-the-art calibrated BOLD technique, the QUantitative O2 (QUO2) approach. We acquired simultaneous measurements of CBF and R2* at rest and during periods of hypercapnia (HC) and hyperoxia (HO) on two separate scan sessions within 24 hours using a clinical 3 T MRI scanner. Maps of M, OEF, oxygen delivery and CMRO(2), were estimated from the measured end-tidal O(2), CBF(0,) CBF(HC/HO) and R2*(HC/HO). Variability was assessed by computing the between-subject coefficients of variation (bwCV) and within-subject CV (wsCV) in seven ROIs. All tests GM-averaged values of CBF(0), M, OEF, O(2) delivery and CMRO(2) were: 49.5 ± 6.4 mL/100 g/min, 4.69 ± 0.91%, 0.37 ± 0.06, 377 ± 51 μmol/100 g/min and 143 ± 34 μmol/100 g/min respectively. The variability of parameter estimates was found to be the lowest when averaged throughout all GM, with general trends toward higher CVs when averaged over smaller regions. Among the MRI measurements, the most reproducible across scans was R2*(0) (wsCV(GM) = 0.33%) along with CBF(0) (wsCV(GM) = 3.88%) and R2*(HC) (wsCV(GM) = 6.7%). CBF(HC) and R2*(HO) were found to have a higher intra-subject variability (wsCV(GM) = 22.4% and wsCV(GM) = 16% respectively), which is likely due to propagation of random measurement errors, especially for CBF(HC) due to the low contrast-to-noise ratio intrinsic to ASL. Reproducibility of the QUO2 derived estimates were computed, yielding a GM intra-subject reproducibility of 3.87% for O(2) delivery, 16.8% for the M value, 13.6% for OEF and 15.2% for CMRO(2). Although these results focus on the precision of the QUO2 method, rather than the accuracy, the information will be useful for calculation of statistical power in future validation studies and ultimately for research applications of the method. The higher test-retest variability for the more extensively modeled parameters (M, OEF, and CMRO(2)) highlights the need for further improvement of acquisition methods to reduce noise levels.