Dynamics of changes in blood flow, volume, and oxygenation: implications for dynamic functional magnetic resonance imaging calibration

Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood-oxygenation level dependent (BOLD)) during functional activation are important for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo2) from calibrated functional MRI (fMRI). An important part of this process is the CBF/CBV relationship, which is signified by a power-law parameter: γ = ln (1 + ΔCBV/CBV)ln (1 + ΔCBF/CBF). Because of difficulty in measuring CBF and CBV with MRI, the value of γ is therefore assumed to be ~0.4 from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is important to know if the value of γ varies after stimulation onset. We measured transient relationships between ΔCBF, ΔCBV, and ΔBOLD by multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat somatosensory cortex during forepaw stimulation, where the stimulus duration ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the administration of the contrast agent for CBV measurements in the same subjects. We observed that the relationship between ΔCBF and ΔCBV varied dynamically from stimulation onset for all stimulus durations. Typically after stimulation onset and at the peak or plateau of the ΔCBF, the value of γ ranged between 0.1 and 0.2. However, after stimulation offset, the value of γ increased to 0.4 primarily because of rapid and slow decays in ΔCBF and ΔCBV, respectively. These results suggest caution in using dynamic measurements of ΔCBF and ΔBOLD required for calculating ΔCMRo2 for functional stimulation, when either ΔCBV has not been accurately measured or a fixed value of γ during hypercapnia perturbation is used.