Improved fMRI calibration: precisely controlled hyperoxic versus hypercapnic stimuli.

The calibration of functional magnetic resonance imaging (fMRI) for the estimation of neuronal activation-induced changes in cerebral metabolic rate of oxygen (CMRO(2)) has been achieved through hypercapnic-induced iso-metabolic increases in cerebral blood flow (CBF). Hypercapnia (HC) has been traditionally implemented through alterations in the fixed inspired fractional concentrations of carbon dioxide (F(I)CO(2)) without otherwise controlling end-tidal partial pressures of carbon dioxide (P(ET)CO(2)) or oxygen (P(ET)O(2)). There are several shortcomings to the use of this manual HC method that may be improved by using precise targeting of P(ET)CO(2) while maintaining iso-oxia. Similarly, precise control of blood gases can be used to induce isocapnic hyperoxia (HO) to reduce venous deoxyhaemoglobin (dHb) and thus increase BOLD signals, without appreciably altering CMRO(2) or CBF. The aim of our study was to use precise end-tidal targeting to compare the calibration of BOLD signals under an isocapnic hyperoxic protocol (HOP) (rises in P(ET)O(2) to 140, 240 and 340 mm Hg from baseline) to that of an iso-oxic hypercapnic protocol (HCP) (rises in P(ET)CO(2) of 3, 5, 7 and 9 mm Hg from baseline). Nine healthy volunteers were imaged at 3T while monitoring end-tidal gas concentrations and simultaneously measuring BOLD and CBF signals, via arterial spin labeling (ASL), during graded HCP and HOP, alternating with normocapnic states in a blocked experimental design. The variability of the calibration constant obtained under HOP (M(HOP)) was 0.3-0.5 that of the HCP one (M(HCP)). In addition, M-variances with precise gas targeting (M(HCP) and M(HOP)) were less than those reported in studies using traditional F(I)CO(2) and F(I)O(2) methods (M(HC) and M(HO), respectively). We conclude that precise controlled gas delivery markedly improves BOLD-calibration for fMRI studies of oxygen metabolism with both the HCP and the more precise HOP-alternative.