| The research forming the basis of this thesis began through a study designed to study the effects of various pharmacological agents on vasculature in animal models. In order to achieve this goal a system was developed that would allow researchers to image vessels using fluorescence angiography.; The angiography involves using a dye, indocyanine green (ICG) which has been used in the clinical setting for over 40 years to study cardiac output, hepatic function and choroidal blood flow in the eye. The initial work was performed on murine femoral arteries and subsequently studies were completed on coronary vessels in the porcine model. The resulting angiograms were of very high quality with respect to their qualitative data. However, quantitative analysis of vessel diameter proved to be a much more arduous task. The software utilized to perform the function of calculating vessel diameter is effective in the static environment where there is no motion of the vessel; however, in the in vivo setting the ability to register images so as to allow the tracking of vessels over time was not possible. As such the initial hypothesis that such a system could be used in vivo to study the effects of agents on vessel diameter was not successfully proven.; The angiograms generated however, were studied and it was determined that such a system could potentially be invaluable if it could be used in the surgical setting for determining graft patency during coronary artery bypass graft (CABG) surgery in humans. Approximately one million patients undergo CABG surgery on an annual basis. The focus, thus shifted to adapt the system for this purpose and subsequently a system was developed that could be used in the operating room that would allow cardiac surgeons to obtain real time intra-operative angiograms demonstrating whether the grafts they had just constructed were patent.; The impact of the technology in initial human studies performed was significant. It was found that in 5-8% of cases graft revision was required based on the angiograms. These angiograms allowed the surgeons to correct the defects prior to closing the patient, thereby, improving the efficacy of the treatment. The tremendous interest in the system subsequently lead to endeavors to commercialize the technology in which regulatory approval was sought in Canada, Europe, Japan and the United States in order that the system could be marketed. In addition, studies were continued at multiple sites in the United Kingdom, Japan, Italy, Switzerland and Canada to demonstrate efficacy and safety.; The system has been used to date in over 1000 patients worldwide and a company, Novadaq Technologies has been formed to commercialize the technology and develop further applications. |
