Sources of systematic bias in hypercapnia-calibrated functional MRI estimation of oxygen metabolism

Abstract

The change in cerebral rate of oxidative metabolism (CMR O 2 ) during neural activation may be estimated from blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and arterial spin-labeling (ASL) fMRI measurements. The established method relies on an epoch of iso-metabolic blood flow increase, typically induced by CO 2 breathing, to calibrate the BOLD−CBF relationship at resting-state CMR O 2 . Here, we discuss the systematic bias in CMR O 2 −CBF data that can be introduced depending on the value derived for the calibration constant ( M) from the CO 2 breathing epoch. We demonstrate that the fidelity of BOLD–CBF data acquired during the neural activation task have low impact on the tightness of CMR O 2 −CBF coupling, as well as the coupling slope, when the derived calibration value is of a relatively moderate amplitude ( M in the range of, or greater than, 10–15 at 1.5 T). Via the standard reformulation of a grid in BOLD–CBF space into the CMR O 2 –CBF plane, we demonstrate the non-linear transformation that takes place and the sources of systematic bias that result. We find that the outcome of a neurovascular coupling study may be predicted to a large extent purely from the value of the calibration constant, M, that is used. Our results suggest that the accurate determination of M is of greater importance than thought previously and indicate that BOLD−CBF data must always be supplied when considering CMR O 2 −CBF behavior in a particular brain region.