Emerging photonic technologies, such as ultrafast lasers, provide a new paradigm for overcoming the limitations of traditional biomedical imaging modalities. In this project, we propose to develop in-line x-ray phase-contrast micro-CT system that will utilize an ultrafast laser-based x-ray (ULX) source. This new source produces x-rays through irradiation of a solid target by the laser beam. Any solid (metal or non-metal) can be used as a target. ULX delivers more power in x-rays than a conventional microfocal tube is able to provide, thus allowing for much faster scans. Further, ULX generates narrow x-ray spectra that consist mainly of characteristic lines. These can be easily tailored (by changing laser beam target) to the imaging task. The phase-contrast micro-CT will allow high-resolution measurements of the spatial distribution of the real (x-ray phase-shift) and the imaginary (x-ray absorption) components of the x-ray refractive index in a living animal. This is in contrast to conventional micro-CT, using a microfocal x-ray tube, which can only map 3D distribution of the x-ray absorption coefficient. Therefore, we expect that'opening the new channel of information provided by the x-ray phase-shift 3D mapping, in addition to conventional absorption map measurement, will significantly increase soft tissue low-contrast resolution of micro-CT without any dose increase, thus allowing improved imaging of cancer in small animal models. In due course, this method could be expanded to clinical CT scanners, providing that the high average power ultrafast lasers become available. Compact, robust, ultrafast lasers are commercially available, and their characteristics are rapidly improving. We plan to construct and explore imaging performance of an in vivo in-line x-ray phase-contrast ULX micro-CT system. This goal will be accomplished by completing the following tasks: i) design and optimization via computer simulations of the optimal system geometry and the focal spot size and shape; ii) design and optimization via computer simulations of ULX spectra; iii) experimental implementation and optimization of the selected system design; iv) development of image processing tools for correction, extraction, enhancement, and fusion of the extracted phase-contrast and absorption tomographic data and improved fusion of absorption and phase-contrast images; v) assemble a cone-beam ULX phase-contrast micro-CT system (with optimized geometry, energy, focal spot, and detector) and begin exploration of the imaging performance of the whole system and comparison with conventional micro-CT, using phantoms and in vivo imaging of oral cancer mouse model.
