Dynamic Gd-DTPA enhanced MRI as a surrogate marker of angiogenesis in tissue-engineered bladder constructs: A feasibility study in rabbits

Abstract

Purpose: To evaluate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess angiogenesis in tissue-engineered bladder constructs in a blinded animal study, and compare different analysis approaches and their correlation with microvessel density (MVD). Materials and Methods: Constructs fortified with vascular endothelial growth factor (VEGF) for enhanced vascularity were grafted onto the bladder in nine rabbits. DCE-MRI of Gd-DTPA uptake was performed and analyzed using Tofts' model, the area under the concentration time curve (AUC), and the uptake slope. DCE-MRI parameters were compared to MVD determined with CD31 immunohistochemistry. Results: Significantly increased MVD was found in the high VEGF group (20 ng/g of tissue) but not at low VEGF (10 ng/g) (2.3× increase, P = 0.035 vs. 1.1× over control). Enhanced permeability at low VEGF was suggested by elevated Ktrans, but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC8min (r = 0.705, P = 0.034). Furthermore, AUC8min provided the most precise discrimination between different VEGF preparations and was the only parameter to show a significant increase (P = 0.0058) consistent with MVD changes at high VEGF. Conclusion: Findings support DCE-MRI for evaluating angiogenesis in bladder constructs and suggest vessel changes other than density. Future studies should incorporate larger contrast agents and permeability assessment to devise an optimal DCE-MRI strategy. © 2005 Wlley-Liss, Inc.