Embodiments of the invention relate to omni-tomographic imaging or grand fusion imaging, i.e., large scale fusion of simultaneous data acquisition from multiple imaging modalities such as CT, MRI, PET, SPECT, US, and optical imaging. A preferred omni-tomography system of the invention comprises two or more imaging modalities operably configured for concurrent signal acquisition for performing ROI-targeted reconstruction and contained in a single gantry with a first inner ring as a permanent magnet a second middle ring containing an x-ray tube, detector array, and a pair of SPECT detectors and a third outer ring for containing PET crystals and electronics. Omni-tomography offers great synergy in vivo for diagnosis, intervention, and drug development, and can be made versatile and cost-effective, and as such is expected to become an unprecedented imaging platform for development of systems biology and modern medicine.