Validation of the hypercapnic calibrated fMRI method using DOT-fMRI fusion imaging

Calibrated functional magnetic resonance imaging (fMRI) is a widely used method to investigate brain function in terms of physiological quantities such as the cerebral metabolic rate of oxygen (CMRO ₂ ). The first and one of the most common methods of fMRI calibration is hypercapnic calibration. This is achieved via simultaneous measures of the blood-oxygenation-level dependent (BOLD) and the arterial spin labeling (ASL) signals during a functional task that evokes regional changes in CMRO ₂ . A subsequent acquisition is then required during which the subject inhales carbon dioxide for short periods of time. A calibration constant, typically labeled M, is then estimated from the hypercapnic data and is subsequently used together with the BOLD-ASL recordings to compute evoked changes in CMRO ₂ during the functional task. The computation of M assumes a constant CMRO ₂ during the CO ₂ inhalation, an assumption that has been questioned since the origin of calibrated fMRI. In this study we used diffuse optical tomography (DOT) together with BOLD and ASL - an alternative calibration method that does not require any gas manipulation and therefore no constant CMRO ₂ assumption - to cross-validate the estimation of M obtained from a traditional hypercapnic calibration. We found a high correlation between the M values (R=0.87, p<0.01) estimated using these two approaches. The findings serve to validate the hypercapnic fMRI calibration technique and suggest that the inter-subject variability routinely obtained for M is reproducible with an alternative method and might therefore reflect inter-subject physiological variability.