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It is commonly assumed that equilibrium transcytolemmal water exchange in tissue is sufficiently frequent as to be fast on any NMR time scale achievable with an extracellular contrast agent (CR) in vivo. A survey of literature values for cell membrane diffusional permeability coefficients (P) and cell sizes suggests that this should not really be so. To evaluate this issue experimentally, we used a programmed intravenous CR infusion protocol for the rat with several rate plateaus, each of which achieved an increased steady-state concentration of GdDTPA 2-in the blood plasma. Interleaved rigorous measurements of 1 H 2 O inversion recoveries were made from arterial blood and from a region of homogeneous thigh muscle tissue throughout the CR infusion. We made careful relaxographic analyses for the blood and muscle 1 H 2 O longitudinal relaxation times. The combined data from several animals were evaluated with a two-site model for equilibrium transcytolemmal water exchange.

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