A novel angiographic methodology for the quantification of angiogenesis

The objective is to develop a method to quantify the dynamic information of contrast transport using angiography for investigating angiogenic treatments. In the rabbit hindlimb ischemia model, contrast media transport was examined for both arteries and the microvasculature. Time histories of image intensity were constructed and modeled. The differences in contrast transport quantified by the parameters of the mathematical model were statistically compared between animals treated with an adenoviral vector that expressed vascular endothelial growth factor and untreated animals. The data reveal that after one week of ischemia, treated animals have a statistical increase in the number of large vessels that convect blood more efficiently. This analysis further shows a statistically significant increase in the angiographic blush in the treated animals. A methodology is described that offers the capability of examining the number and geometry of large arteries, the dynamics of contrast transport, and the amount of angiographic blush that is related to microvascular density. In therapeutic angiogenesis, numerous techniques are used to measure variables such as the angiographic score, capillary density, and regional blood flow. The analysis presented herein can offer information of these variables, and is transferable from the laboratory to the clinical arena.