"This proposal offers to combine X-ray CT (XCT) and Fluorescence Molecular Tomography (FMT) into a hybrid, quantitative system and method. The project builds on state-of the-art knowledge that only recently became available in different European states as represented by the partners herein. In return it delivers the first such hybrid system worldwide. The system will operate by 1) co-registering XCT images with highly performing FMT images for merging anatomical, functional and molecular contrast and by 2) combining XCT information into the FMT inversion to provide a system with superior imaging performance. XCT-based correction, as explained in this proposal, can improve FMT performance in a more radical way than corresponding “correction methods” used for improving PET or SPECT images. In this way FMT-XCT can reach the imaging accuracy of radio-nuclei-based tomography hybrid systems. By using fluorescence, FMT-XCT can then enable high flexibility in targeting physiology and molecular function, especially in multi-spectral mode, and high dissemination potential because virtually any biomedical laboratory has access to fluorescence reporting, compared to radio-nuclei based research that requires access to radiochemistry and cyclotron facilities. FMT-XCT aims in advancing small animal imaging and drug discovery with a view towards the clinical application on non-invasive breast cancer imaging. For this reason, focus herein is given to imaging breast cancer and response to therapy. Overall the technology is ideally suited for commercial translation and has the potential to become the method of choice for in-vivo imaging in most biomedical laboratories and in select clinical applications. While it appreciates the value of nuclear imaging methods, this proposal will hopefully raise the funding necessary to establish on European ground a new potent paradigm of in-vivo imaging with high dissemination and application potential and large social and health-care impact ."