Improving quantitative BOLD-based measures of oxygen extraction fraction using hyperoxia BOLD-derived measures of...

Streamlined quantitative BOLD (sqBOLD) is a refinement of the quantitative BOLD (qBOLD) technique capable of producing noninvasive and quantitative maps of oxygen extraction fraction (OEF) in a clinically feasible scan time. However, sqBOLD measurements of OEF have been reported as being systematically lower than expected in healthy brain. Because the qBOLD framework infers OEF from the ratio of the reversible transverse relaxation rate ( $R_2^{\text{'}}$ ) and deoxygenated blood volume (DBV), this underestimation has been attributed the overestimation of DBV. Therefore, this study proposes the use of an independent measure of DBV using hyperoxia BOLD and investigates whether this results in improved estimates of OEF.

Monte Carlo simulations were used to simulate the qBOLD and hyperoxia-BOLD signals and to compare the systematic and noise-related errors of sqBOLD and the new hyperoxia-qBOLD (hqBOLD) technique. Experimentally, sqBOLD and hqBOLD measurements were performed and compared with TRUST (T₂ relaxation under spin tagging)-based oximetry in the sagittal sinus.

Simulations showed a large improvement in the uncertainty of DBV measurements, leading to a much improved dynamic range for OEF measurements with hqBOLD. In a group of 10 healthy volunteers, hqBOLD produced measurements of OEF in cortical gray matter (OEF_hqBOLD = 38.1 ± 10.1%) that were not significantly different from TRUST oximetry measures (OEF_TRUST = 40.4 ± 7.7%), whereas sqBOLD-derived measures (OEF_sqBOLD = 16.1 ± 3.1%) were found to be significantly different.

The simulations and experiments in this study demonstrate that an independent measure of DBV provides improved estimates of OEF.