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Time domain imaging is presented as a method to perform in vivo fluorophore concentration reconstructions in the presence of varying lifetimes. In particular, using the SAMI™platform, target and endogenous fluorescence are shown to be distinguishable. Reconstruction of a solid Cy5.5 subcutaneous inclusion in a mouse is done with background endogenous fluorescence originating from the food in the stomach. The discrimination between both sources of fluorescence is done by a simple method thereby providing a better reconstruction.