Quantifying angiogenesis in VEGF-enhanced tissue-engineered bladder constructs by dynamic contrast-enhanced MRI using contrast agents of different molecular weights
✍ Scribed by Hai-Ling Margaret Cheng; Chad Wallis; Zhiping Shou; Walid A. Farhat
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 469 KB
- Volume
- 25
- Category
- Article
- ISSN
- 1053-1807
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✦ Synopsis
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. J. Magn. Reson. Imaging 2007. © 2006 Wiley‐Liss, Inc.