Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal

In comparison to the well‐documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood‐oxygen‐level‐dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen‐treated serum were 0.22 mM−1 · s−1and 0.19 mM−1 · s−1, respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18–42% of measured brain regions, voxels with accompanying significant decreases in both the T2* (−12.1% to −19.4%) and T1 (−5.8% to −3.3%) relaxation times. In contrast, the T2* relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41–50% of the measured brain), which reflected a hyperoxygenation‐induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia‐driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen‐induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, −9.8% to −12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia. Copyright © 2014 John Wiley & Sons, Ltd. This study investigated the influence of the paramagnetic effect of dissolved oxygen in hyperoxia on BOLD signal contrast. Hyperoxia‐driven negative BOLD contrast was frequently observed in the subcortical area, in which both T2* and T1 relaxation significantly decreased. In contrast, voxels with positive BOLD contrast showed significantly increased T2* relaxation time, which reflects decreased concentration of deoxyhemoglobin. Transient hypoxia applied during hyperoxic respiration reverted B