High resolution laboratory x-ray tomography for biomedical research : From design to application

Abstract: Laboratory x-ray micro- and nano-tomography are emerging techniques in biomedical research. Through the use of phase-contrast, sufficient contrast can be achieved in soft tissue to support medical studies. With ongoing developments of x-ray sources and detectors, biomedical studies can increasingly be performed at the laboratory and do not necessary require synchrotron radiation. Particularly nano-focus x-ray sources offer new possibilities for the study of soft tissue. However, with increasing resolution, the complexity and stability requirements on laboratory systems advance as well. This thesis describes the design and implementation of two systems: a micro- CT and a nano-CT, which are used for biomedical imaging.To increase the resolution of the micro-CT, super-resolution imaging is adopted and evaluated for x-ray ima- ging, grating-based imaging and computed tomography utilising electromagnetic stepping of the x-ray source to acquire shifted low-resolution images to estimate a high-resolution image. The experiments have shown that super-resolution can significantly improve the resolution in 2D and 3D imaging, but also that upscaling during the reconstruction can be a viable approach in tomography, which does not require additional images.Element-specific information can be obtained by using photon counting detectors with energy-discriminating thresholds. By performing a material decomposition, a dataset can be split into multiple different materials. Tissue contains a variety of elements with absorption edges in the range of 4 – 11 keV, which can be identified by placing energy thresholds just below and above these edges, as we have demonstrated using human atherosclerotic plaques.An evaluation of radiopaque dyes as alternative contrast agent to identify vessels in lung tissue was performed using phase contrast micro-tomography. We showed that the dye solutions have a sufficiently low density to not cause any artefacts while still being able to separate them from the tissue and distinguish them from each other.Finally, the design and implementation of the nano-CT system is discussed. The system performance is assessed in 2D and 3D, achieving sub-micron resolution and satisfactory tissue contrast through phase contrast. Applica- tion examples are presented using lung tissue, a mouse heart, and freeze dried leaves.