Mapping Water Exchange Rates in Rat Tumor Xenografts Using the Late-Stage Uptake Following Bolus Injections of Contrast Agent

PurposeTo map the intra-to-extracellular water exchange rate constant in rat xenografts using a two-compartment model of relaxation with water exchange and a range of contrast agent concentrations and compare with histology. MethodsMDA-MB-231 cells were xenografted into six nude rats. Three bolus injections of gadodiamide were administered. When uptake in the tumor demonstrated a steady-state, T-1 data were acquired by spoiled gradient recalled acquisitions at four flip angles. A global fit of data to a two-compartment model incorporating exchange was performed, assuming a distribution volume of 20% of the rat. ResultsVoxels that did not reach steady-state and were excluded from parametric maps tended to be in large necrotic areas. TUNEL-negative (nonapoptotic) regions tended to have well-defined error bounds, with an average intra-to-extracellular exchange rate constant of 0.6 s(-1). Apoptotic regions had higher exchange, but poorly determined upper bounds, with goodness of fit similar to that for a model assuming infinitely fast exchange. A lower bound of >3 s(-1) was used to establish voxels where the exchange rate constant was fast despite a large upper bound. ConclusionWater exchange rates were higher in apoptotic regions, but examination of statistical errors was an important step in the mapping process. Magn Reson Med 71:1874-1887, 2014. (c) 2013 Wiley Periodicals, Inc.