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Bioluminescence imaging (BLI) makes it possible to elucidate molecular and cellular signatures to better understand the effects of human disease in small animal models in vivo. The unambiguous three-dimensional bioluminescent source information obtained by bioluminescence tomography (BLT) could further facilitate its applications in biomedicine. However, to the best of our knowledge, the existing gradient-type reconstruction methods in BLT are inefficient, and often require a relatively small volume of interest (VOI) for feasible results. In this paper, a fast generalized graph cuts based reconstruction method for BLT is presented, which is to localize the bioluminescent source in heterogeneous mouse tissues via max-flow/min-cut algorithm. Since the original graph cuts theory can only handle graph-representable problem, the quadratic pseudo-boolean optimization is incorporated to make the graph …