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


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) (2.3x increase, P = 0.035 vs. 1.1x over control). Enhanced permeability at low VEGF was suggested by elevated K(trans), but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC(8min) (r = 0.705, P = 0.034). Furthermore, AUC(8min) 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.


CONCLUSIONS
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.
Cheng
Hai-Ling Margaret
HL
Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. hai-ling.cheng@sickkids.ca
Chen
Jun
J
Babyn
Paul S
PS
Farhat
Walid A
WA
D000818:Animals; D003287:Contrast Media; D005240:Feasibility Studies; D005260:Female; D019786:Gadolinium DTPA; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011817:Rabbits; D023822:Tissue Engineering; D001743:Urinary Bladder / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D003287:Contrast Media; D042461:Vascular Endothelial Growth Factor A; D019786:Gadolinium DTPA