Detection of areas with viable remnant tumor in postchemotherapy patients with Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokineticmodeling

An approach is presented for monitoring the effects of neoadjuvant chemothe rapy in patients with Ewing's sarcoma using dynamic contrast-enhanced perfu sion magnetic resonance (MR) images. For that purpose, we modify the three- compartment pharmacokinetic permeability model introduced by Tofts et al. ( Magn Reson Med 1991;17:357-67) to a two-compartment model. Perfusion MR ima ges acquired using an intravenous injection with Gadolinium (Gd-DTPA) are a nalyzed with this two-compartment pharmacokinetic model as well as the with an extended pharmacokinetic model that includes the (local) arrival time t (o) of the tracer as an endogenous (estimated) parameter. For each MR secti on, a wash-in parameter associated with each voxel is estimated twice by fi tting each of the two pharmacokinetic models to the dynamic MR signal. A co mparison of the two wash-in parametric images (global versus local arrival time) with matched histologic macroslices demonstrates a good correspondenc e between areas with viable remnant tumor and a high wash-in rate. This can be explained by the high number and permeability of the (leaking) capillar ies in viable tumor tissue. The novel pharmacokinetic model based on a loca l arrival time of tracer results in the best fit of the wash-in rate, the m ost important factor discerning viable from nonviable tumor components, How ever, parameter estimates obtained with this model are also more sensitive to noise in the MR signal, The novel pharmacokinetic model resulted in a se nsitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The m odel based on a global arrival time gave sensitivities between 0.33 and 0.7 7 and specificities between 0.58 and 0.99. Both statistics are computed as the fraction of correctly labeled voxels (viable or nonviable tumor) within a specified ROI, which delineates the tumor. We conclude that the added va lue of estimating the local arrival time of tracer first manifests itself f or moderate noise levels in the MR signal. The novel pharmacokinetic model should moreover be preferred when pharmacokinetic modeling is applied on th e average signal intensity within a ROI, where noise has less effect on the fitted parameters. (C) 2000 Elsevier Science Inc. All rights reserved.