Angiographic quantification of gene therapy induced angiogenesis
Date of Award
Doctor of Philosophy (Ph.D.)
First Committee Member
Baruch B. Lieber, Committee Chair
Therapeutic angiogenesis is the induction of new vessel growth to treat occlusive vascular disease. Gene therapy employed to express various proangiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, is the primary means of therapeutic angiogenesis. Clinical trials of therapeutic angiogenesis to treat peripheral and coronary arterial occlusive diseases have produced mixed results. Small phase 1 clinical trials of angiogenesis induced by plasmids encoded to express proangiogenic factors provided promising outcomes. However, a large, double-blinded, placebo-controlled randomized trial of intracoronary and intravenous injections of recombinant VEGF protein did not sustain significant clinical benefit at one-year follow-up. Thus, much in vitro and in vivo research is currently ongoing to refine techniques of therapeutic angiogenesis.Angiographic assessment of angiogenesis utilized in both the clinical arena and in the research laboratory has been limited to the analysis of singular angiographic images. A novel approach to quantify the level of angiogenesis by modeling the temporal variation of contrast intensity throughout an angiographic sequence has been developed. This methodology involves the analysis of vascular changes that occur in angiographically visible arteries and the microvasculature which appears as angiographic blush. The dynamic information extracted from the images of angiographic sequences may then be mathematically modeled, and the model parameters provide information about the transport of contrast through the specified region of interest. It is hypothesized that these model parameters serve as quantifiable indices of induced angiogenesis.
Gounis, Matthew J., "Angiographic quantification of gene therapy induced angiogenesis" (2004). Dissertations from ProQuest. 2093.