Quantifying angiogenesis in VEGF-enhanced tissue-engineered bladder constructs by dynamic contrast-enhanced MRI using contrast agents of different molecular weights |
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Authors: | Cheng Hai-Ling Margaret Wallis Chad Shou Zhiping Farhat Walid A |
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Affiliation: | Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. hai-ling.cheng@sickkids.ca |
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Abstract: | PURPOSE: To compare Gadomer, a macromolecular magnetic resonance (MR) contrast agent, and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) for quantifying angiogenesis in tissue-engineered bladder constructs. MATERIALS AND METHODS: Constructs enhanced with vascular endothelial growth factor (VEGF) were grafted onto the bladder of 12 rabbits (N= 3/VEGF, VEGF = 0,10,15,20 ng/g tissue). After eight days dynamic contrast-enhanced MRI (DCE-MRI) was performed in each animal using Gadomer and Gd-DTPA, separated by a one-hour interval. DCE-MRI parameters were calculated from two-compartment pharmacokinetics (plasma volume fraction, v(p); transfer constant, K(trans)) and model-free analysis, area under the concentration-time curve (AUC). Histology assessment of microvessel density (MVD) and Evans blue permeability were compared to DCE-MRI. RESULTS: MVD was elevated (P < 0.05) at the highest VEGF but not among lower levels; permeability differences were absent. Contrast enhancement increased with VEGF and was better resolved with Gadomer than Gd-DTPA. Gadomer was the better assay for estimating plasma volume: v(p) provided the best distinction (P < 0.005), but both v(p) and AUC were correlated to MVD. With Gd-DTPA, only AUC distinguished MVD differences (P< 0.05). Changes in K(trans) were insignificant. CONCLUSION: Macromolecular contrast agents are valuable for monitoring angiogenesis in tissue-engineered bladder grafts. Compared to Gd-DTPA, Gadomer provides more accurate and precise quantification of microvessel function, and is better suited to pharmacokinetic analysis for accurate physiological quantification. |
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Keywords: | dynamic contrast‐enhanced MRI macromolecular contrast agents angiogenesis tissue engineering microvessel density permeability |
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