Variation of the relaxographic shutter-speed for transcytolemmal water exchange affects the CR bolus-tracking curve shape

Contrast reagents (CRs) may enter the tissue interstitium for a period after a vascular bolus injection. As the amount of interstitial CR increases, the longitudinal relaxographic NMR shutter-speed (T-1) for the equilibrium transcytolemmal water exchange process increases. The quantity T-1 is given by \r(10)[CRo] + R-1o0 - R-1i\ (where r(1o) and [CRo] represent the interstitial (extracellular) CR relaxivity and concentration, respectively, and R-1o0 and R-1i are the extra- and intracellular (H2O)-H-1 relaxation rate constants, respectively, in the absence of exchange). The increase of T-1 with [CRo] causes the kinetics of the water exchange equilibrium to appear to decrease. Here, analytical theory for two-site-exchange processes is combined with that for pharmacokinetic CR delivery, extraction, and distribution in a method termed BOLus Enhanced Relaxation Overview (BOLERO(C)). The shutter-speed effect alters the shape of the bolus-tracking (B-T) time-course. It is shown that this is mostly accounted for by the inclusion of only one additional parameter, which measures the mean intracellular lifetime of a water molecule. Simulated and real data demonstrate that the effect of shutter-speed variation on pharmacokinetic parameters can be very significant: neglecting this effect can lead to an underestimation of the parameter values by 50%. This phenomenon can be heterogeneous. Within a tiny gliosarcoma implanted in the rat brain, the interstitial CR in the tumor core never rises to a level sufficient to cause apparent slowing of the exchange process. However, within the few microns needed to reach the proliferating rim, this occurs to a significant degree. Thus, even relative pharmacokinetic quantities can be incorrectly represented in a parametric map that neglects this effect. The BOLERO analysis shows promise for in vivo vascular phenotyping in pathophysiology. It also includes a provision for approximating the separation of the perfusion and permeability contributions to CR extravasation. (C) 2003 Wiley-Liss, Inc.