A forward model for CFT imaging simulation was developed. A comparison of forward and inverse schemes on the Digimouse, constructed to mimic high signal in organs of filtration (“Truth”), shows differences for different reconstruction techniques. The liver in the simulated measured image appears artificially dark due to high optical absorption. If each tissue is allowed to have different optical properties for reconstruction, fluorescence is recovered with 2.58% error. If image recovery is performed using one bulk mean tissue value for optical properties, inaccuracy in the liver, kidneys, and brain is visible due to large differences in optical properties, with total fluorescence recovery error of 35.3%.