Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange

For bolus-tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) ¹H₂O relaxation rate constant, R₁/(*) ≡(T₁/(*))^-1. This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R₁/(*) itself can be affected, 2) the resultant non-linear [CR]-dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30-sec, 0.17 mmol/kg dose of GdDTPA^2-, the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS-9L gliosarcoma tumor model.