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

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Abstract
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 |r1o[CRo] + R1o0 – R1i| (where r1o and [CRo] represent the interstitial (extracellular) CR relaxivity and concentration, respectively, and R1o0 and R1i are the extra‐ and intracellular 1H2O 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©). 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. Magn Reson Med 50:1151–1169, 2003.