Dual Modality CT/X-ray Luminescence CT for in vivo Cancer Imaging ABSTRACT A combined X-ray CT and molecular imaging system, referred to as “CT/X-ray luminescence CT (XLCT)”, is proposed. The system uses X-ray as a single source to image anatomy and molecular features from simultaneous detection of luminescence signals of X-ray activatable molecular probes. In this technique, the spatial information is obtained by exciting the sample using spatially selective X-ray patterns while optical detectors placed around the sample measure luminescence photons diffusing out. Regardless of where these photons are detected, it is known that they are created somewhere on the path of the coded X-ray beams. This fundamental principle constitutes a new paradigm for imaging deep-seated light-emitting probes, with little background from tissue auto-fluorescence. Another significant advantage of XLCT is that X-ray excitation is amplified by orders of magnitude because of the extremely high quantum yield (2-4 orders of magnitude greater than 100%) of the radioluminescent materials. Toward establishing XLCT for various biomedical applications and eventually for clinical applications, we have assembled a multidisciplinary team consisting of leading investigators with expertise in CT imaging, molecular imaging, biochemistry, medical physics, computational science, and medicine, and established research themes that unify the common interests and expertise of these investigators. If successful, the hybrid CT/XLCT will overcome many of the limitations of CT and optical imaging methods and enable us to visualize biological processes in the anatomical CT image context with unprecedented sensitivity, specificity and spatial resolution. The novel dual modality imaging strategy will therefore significantly advance the field of cancer imaging and provide a valuable imaging tool for biological and clinical studies.