ANALYSIS OF SUBCUTANEOUS ANGIOGENESIS BY GRADIENT-ECHO MAGNETIC-RESONANCE-IMAGING

The goal of this study was to develop an experimental method for nonin vasive analysis of angiogenesis, namely the sprouting of capillaries f rom existing blood vessels. Angiogenesis was assayed in the subcutaneo us vasculature of nude mice in a region of 3 x 3 cm that included in i ts center a defined angiogenic stimulus, Angiogenic stimuli included a garose beads containing angiogenic growth factors, multicellular tumor spheroids, and dermal incisions. Highly significant correlation (r = 0.905, P = 0.0001) was found between the apparent vessel density deter mined by gradient echo MRI and the density of blood-containing vessels determined postmortem, The functionality of the neovasculature was de monstrated in mice breathing alternatingly carbogen or 95% air/5% CO2. Large signal enhancement with carbogen breathing corresponded to regi ons of high vessel density, The assay reported here can be applied for the study of dermal wound healing, primary vascularization of subcuta neous implants, and for measuring the activity of angiogenic and antia ngiogenic agents.