Fig. (1).

The Ideal Multiple Indicator Dilution (MID) experiment, an example of multiscale modeling: (left panel: linear scale; right panel: semilog scale) A set of 4 indicators are injected as a bolus into the inflow. The impulse response function, h(t), is subscripted: S is the solute of interest metabolized intracellularly, N is its non-consumed analog that is also transported; E is the extracellular reference and V the intravascular one. E compared to V gives capillary permeability. N compared to E gives cell permeability, S compared to N gives intracellular metabolic reaction rate. The levels of modeling cover intracellular reaction sequences in two cell types (endothelial cell and the tissue’s parenchymal cells) and two extracellular spaces, the plasma and the interstitial fluid space. The processes include convective transport along a spatially distributed capillary-tissue exchange unit, axial diffusion, radial permeation via passive and transporter-mediated processes. (Curves computed from a 4-region, 4-solute model [43]).