An apparatus for providing an integrated tri-modality system includes a fluorescence tomography subsystem (FT), a diffuse optical tomography subsystem (DOT), and an x-ray tomography subsystem (XCT), where each subsystem is combined in the integrated tri-modality system to perform quantitative fluorescence tomography with the fluorescence tomography subsystem (FT) using multimodality imaging with the x-ray tomography subsystem (XCT) providing XCT anatomical information as structural a priori data to the integrated tri-modality system, while the diffuse optical tomography subsystem (DOT) provides optical background heterogeneity information from DOT measurements to the integrated tri-modality system as functional a priori data. A method includes using FT, DOT, and XCT in an integrated fashion wherein DOT data is acquired to recover the optical property of the whole medium to accurately describe photon propagation in tissue, where structural limitations are derived from XCT, and accurate fluorescence concentration and lifetime parameters are recovered to form an accurate image.