Transit time mean and variance are markers of vascular network structure, wall shear stress distribution and oxygen extraction fraction.

Abstract

Perfusion measurements provide information about flow magnitude, but more detailed information is found from transit time distributions (TTD). Whether TTDs provide intrinsic (flow-independent) information about vascular geometry or just flow field remains unknown. We propose a new approach to calculate TTD, based on wall shear stress (WSS). We show that constant WSS yields zero-variance TTD. Simulations in statistical networks show that mean transit time (MTT) and capillary transit time heterogeneity (CTH) are primarily determined by pathway number distribution rather than pressure drop distribution. Using 1000 statistically generated cortical columns, we show that (1) the central volume theorem provides a very good approximation for MTT, hence is a measure of tissue permeability; (2) CTH/MTT ratio, RTH (relative transit time heterogeneity), is a marker of WSS variability; and (3) RTH is inversely related to network oxygen extraction fraction (OEF) but only weakly related to MTT. RTH is below one in animal models, but above one in humans, indicating that WSS distribution is tighter in small animals (lower RTH and higher OEF), due to higher metabolic rate. Human WSS distribution appears to be an inherent property, since simulations show much larger RTH. Finally, WSS distribution is unaffected in ageing, but altered in pathology.