"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
Optical Diffusion Tomography, with Application to In Vivo Fluorescence Resonance Energy Transfer Imaging
Kevin Webb, Purdue University
Optical sensing and imaging will continue to become more important for in vivo medicine. In most cases, light can be modeled with a diffusion equation, and the reconstruction of images based on this model is the basis of optical diffusion tomography (ODT). Enhanced contrast can be achieved with targeting of a fluorophore to cancer cells, for example, and targeted anti-cancer drugs can be delivered. Another molecular imaging opportunity involves fluorescence resonance energy transfer (FRET) parameters. FRET has proved to be of immense value in the study of chemical transport into cells and the underlying cause of disease, and by coupling to ODT (FRET-ODT), there is the opportunity to transfer this knowledge to in vivo studies. While substantial progress has been made in various ODT modalities, the achievable resolution and the computational burden impede effective applications. More efficient imaging strategies are thus essential.
This research involves the development of a method for deep tissue imaging of FRET parameters (FRET-ODT) and fast, accurate and robust methods for optical diffusion tomography. The recent demonstration by the Webb group that it is possible to image FRET parameters using heavily scattered light is being expanded into a method for imaging FRET in vivo. This involves a solution for the intramolecular FRET parameters with both rigid and flexible linkers that are incorporated as unknown sources in a diffusion equation representation for the donor fluorescence. Multigrid algorithms are being developed and applied to fluorescence imaging and FRET-ODT. A model-based non-iterative image reconstruction method, that has proved to substantially reduce computation time in preliminary studies, is being applied to image FRET kinetic parameters.
