Relation between Cerebral Blood Flow and Metabolism Explained by a Model of Oxygen Exchange

Abstract

The cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are major determinants of the contrast in functional magnetic resonance imaging and optical imaging. However, the coupling between CBF and CMRO2 during cerebral activation remains controversial. Whereas most of the previous models tend to show a nonlinear coupling, experimental studies have led to conflicting conclusions. A physiologic model was developed of oxygen transport through the blood–brain barrier (BBB) for dynamic and stationary states. Common model simplifications are proposed and their implications for the CBF/CMRO2 relation are studied. The tissue oxygen pool, the BBB permeability, and the hemoglobin dissociation curve are physiologic parameters directly involved in the CBF/CMRO2 relation. We have been shown that the hypothesis of a negligible tissue oxygen pool, which was admitted by most of the previous models, implies a tight coupling between CBF and CMRO2. By relaxing this hypothesis, a real uncoupling was allowed that gives a more coherent view of the CBF/CMRO2 relation, in better agreement with the hypercapnia data and with the variability reported in experimental works for the relative changes of those two variables. This also allows a temporal mismatch between CBF and CMRO2, which influences the temporal shape of oxygenation at the capillary end.