The degree of heterogeneity in metabolic demand and blood flow as measured by PET

It has been believed that direct and accurate assessment of local CMRO2 and CBF is feasible using 15O-labeled oxygen and PET in vivo. This is true, provided that the local radioactivity concentration is measured accurately, and that the kinetics of 15O-oxygen is well modeled by a suitable model formulation. The fact is that the 15O-oxygen is metabolized in the brain instantaneously to become a labeled-water, being cleared by CBF, and that the metabolized water contributes to the PET assessment, thus requiring a correction for this process. A recent technique has enabled shortening the examination time, and demonstrated a relationship of transient changes of oxygen demand and blood flow during various physiological and/or patho-physiological conditions. Experiments during neuronal activations or during decreased oxygen delivery demonstrated evidences that changes of CBF are not controlled to directly (or stoichiometrically) couple with those of CMRO2, and suggested that magnitude of the uncoupling depends on several physiological factors such as oxygen availability, capillary structure and hemoglobin contents. Effective oxygen diffusiibility (EOD) has been proposed as an index to clarify the oxygen diffusion process between the capillary and cerebral tissue. Theoretical simulation also suggested possible error sources in the methodology which could be responsible to clarify the regional variation of the CMRO2/CBF uncoupling.