Intravascular Fluorescence lifetime characterization of Atherosclerosis

Fluorescence lifetime imaging (FLIm) provides a biochemical signature of tissue based on autofluorescence properties. Here, we developed an integrated FLIm-IVUS imaging catheter system, suitable for the interrogation of coronary arteries in vivo. This includes adapting a pulse sampling acquisition scheme to enable co-registered FLIm-IVUS acquisition and designing, fabricating and testing a motor drive unit and low profile FLIm-IVUS catheter. The ability of this instrument to acquire robust FLIm data in coronary arteries in vivo using conventional percutaneous coronary intervention techniques was evaluated in swine model. Imaging of ex vivo human samples confirmed the benefit of additional accurately co-registered spectroscopic data to IVUS for improved lesion characterization. Optimization of optical and mechanical performance of the catheter was achieved with the development of a monolithic freeform reflective optics that enables improvements in collection efficiency, and lateral resolution in a compact, fluorescence background free element [P2]. Finally, a pilot comparative imaging study of ex vivo human artery samples was performed using the pulse sampling FLIm data acquisition technique, combined with Raman spectroscopy, by means of a bimodal forward-viewing optical probe. Methods were developed for the automated analysis of FLIm contrast sources using Raman spectroscopy data. The development of dedicated intravascular instrumentation combined with further understanding of the information provided by FLIm will improve the relevance of FLIm as a practical tool for the investigation of atherosclerosis. Future work will focus on regulatory activities to enable studies in human subjects, where the ability of FLIm to provide the biochemical signature of lesions in vivo may be leveraged to improve understanding of the disease natural history, develop new drugs, and possibly be used in clinical settings to improve patient treatment.