Experimental measurement of extravascular parenchymal BOLD effects and tissue oxygen extraction fractions using...

Quantitative interpretation of BOLD fMRI signal changes has predominantly employed empirical models for the whole parenchyma and a calibration step is usually needed to determine the physiological parameters during activation. Although analytical expressions are available for the extravascular and intravascular components of the BOLD effects, it is difficult to experimentally separate tissue from blood signal contributions at the low magnetic fields in which most fMRI studies are performed. Even if this can be achieved, an additional problem that remains is the separation of two types of extravascular BOLD effects, namely those around microvasculature (in the parenchyma close to the site of activation) and those around draining macrovasculature (e.g., in tissue and CSF more remote from the site of activation). In the recently developed vascular space occupancy technique, blood signals are nulled and the activations are localized predominantly in gray matter, allowing experimental measurement of parenchymal extravascular R(2)* and its changes accompanying activation. When comparing such data with total parenchymal R(2)* changes in BOLD fMRI, the extravascular fractions were found to be 47 +/- 7% (mean +/- SEM, n = 4) and 67 +/- 6% at 1.5 and 3.0 T, respectively, in line with expectations that intravascular BOLD contributions are reduced at higher field. The present approach provides a noninvasive means to determine parenchymal oxygen extraction fraction (OEF) in situ. During visual stimulation, OEF values measured at 1.5 and 3.0 T were in good agreement, giving 0.23 +/- 0.01 and 0.21 +/- 0.01, respectively.