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 (CMRO2). 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 CMRO2. 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 CMRO2 during the functional task. The computation of M assumes a constant CMRO2 during the CO2 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 CMRO2 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.