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Abstract

The blood oxygen-level dependent (BOLD) functional MRI (fMRI) signal is typically used as a surrogate marker of neuronal activity. While the BOLD signal is a sensitive marker of activity, it is unfortunately also a physiologically ambiguous signal. It arises from a combination of vascular and metabolic sources, and is measured as a relative change from an unknown baseline. Because of this physiological ambiguity, it cannot be compared quantitatively across groups of individuals with different vascular profiles, such as in aging or disease. Calibrated fMRI techniques use the BOLD and blood flow response measured during a breathing manipulation combined with a biophysical model to estimate the relative change in cerebral metabolic rate of O2 consumption (CMRO2) during a task. Here, I will present an extension of previous calibrated fMRI models, the generalized calibration model (GCM), that can be used for any breathing manipulation including changes in O2 and/or CO2 concentration for the more accurate estimation of CMRO2. This model framework was then applied to determine the age-related bias in BOLD-only studies of cognitive aging. In the second part of my talk, I will present additional modeling results using the GCM combined with two or more breathing manipulations for the determination of the oxygen extraction fraction (OEF) and CMRO2 at rest. This technique is promising as it allows the estimation of parameters previously only measurable using positron emission tomography. I will present results obtained at 3 and 7 Tesla and discuss the implication of this technique for future studies of aging and vascular disease, and the impact of exercise and diet on cerebral vascular and metabolic health.