Mapping water exchange rates in rat tumor xenografts using the late-stage uptake following bolus injections of contrast agent

Abstract

Purpose To 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. Methods MDA-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, T1 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. Results Voxels 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. Conclusion Water exchange rates were higher in apoptotic regions, but examination of statistical errors was an important step in the mapping process. © 2013 Wiley Periodicals, Inc.