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Tissue imaging is a pivotal component of both biomedical research and clinical practice. In order to identify tissue structures down to the cellular level, it requires the capability to image mm-size unstained tissue specimens with micron to sub-micron resolution. Tissue imaging is normally performed either using x-rays or visible light. While the latter is limited by light scattering in relatively thick tissues, the former often suffers from poor contrast in absorption-based systems. Phase-contrast x-ray microscopes exist but they often lack the required quantitativeness, entail acquisition times of the order of tens of hours for 3-D imaging and are limited to narrow fields of view. We propose a novel multi-modal phase-based x-ray microscope capable of imaging mm-thick tissue samples on a mm-size field of view using intensity-modulation masks. They act as optical elements allowing the quantitative retrieval of tissue properties such as transmission, refraction and scattering. Additionally, given that the system’s spatial resolution depends only on the mask aperture size, a multi-resolution approach is possible by selecting masks with aperture size matching the resolution requirements (micron and sub-micron) of specific samples. The design and optimization of the x-ray microscope is presented in this paper together with exemplar images of a thin foam sample resulting from the retrieval of the three contrast channels. The final paper will include details of the system parameter optimization (e.g., propagation distance, mask aperture and period), their effect on the retrieval algorithm and imaging performance as well as the first images of biological samples.
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