Improvement of fluorescence-enhanced optical tomography with improved optical filtering and accurate model-based reconstruction algorithms.

The goal of preclinical fluorescence-enhanced optical tomography (FEOT) is to provide three-dimensional fluorophore distribution for a myriad of drug and disease discovery studies in small animals. Effective measurements, as well as fast and robust image reconstruction, are necessary for extensive applications. Compared to bioluminescence tomography (BLT), FEOT may result in improved image quality through higher detected photon count rates. However, background signals that arise from excitation illumination affect the reconstruction quality, especially when tissue fluorophore concentration is low and/or fluorescent target is located deeply in tissues. We show that near-infrared fluorescence (NIRF) imaging with an optimized filter configuration significantly reduces the background noise. Model-based reconstruction with a high-order approximation to the radiative transfer equation further improves the reconstruction quality compared to the diffusion approximation. Improvements in FEOT are demonstrated experimentally using a mouse-shaped phantom with targets of pico- and subpico-mole NIR fluorescent dye.