Identifying Tumor Vascular Permeability Heterogeneity With Magnetic Resonance Imaging Contrast Agents

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Abstract
Aref M, Brechbiel M, Wiener E. Identifying tumor vascular permeability heterogeneity with magnetic resonance imaging contrast agents. Invest Radiol 2002;37:178–192. Dynamic contrast enhanced (DCE) MR mammography (MRM) uses tumor capillary density differences for prognosis. The heterogeneous response of permeability-surface area products (PS = Kp↔t) was examined in mammary tumors, as a function of contrast agent size, to determine what effect ROI size might have on PS and prognosis. DCE FLASH signal intensities were converted to gadolinium concentrations by a standard curve, which was fitted by a two-compartment model for the tumor’s extravascular extracellular space (EES) volume fraction (ve), and the tumor volume normalized transfer rate between plasma and EES (Kp↔t/VT). For Gd-DTPA ve = 9% to 13% Kp↔t/VT = 0.01 to 0.06 minutes−1, and the macromolecular agent, PAMAM-TU-DTPA G = 4 ve = 0.8% to 1% Kp↔t/VT = 0.008 to 0.04 minutes−1. Significant differences in Kp↔t/VT for local regions were found for both agents relative to the whole tumor and the macromolecular agent had greater dynamic range. Smaller ROI values or pixels should yield more accurate assessment of neovascularization.