X-ray and neutron μCT of biomedical samples: from image acquisition to quantification

Even though the validity of x-ray computed tomography in the analysis of biomedical samples is nowadays undisputed, the more recent imaging techniques and more advanced instruments (such as synchrotrons) are still relatively unknown to many medical doctors that could benefit from them.The doctoral work presented in this thesis joins a collective effort from the imaging community to demonstrate potential applications of advanced x-ray and neutron imaging methods to preclinical medical research, with the hope of contributing to reach a “critical mass” in the medical community and in the public opinion as well.Two main lines of work are detailed, one focused on the ex vivo evaluation of corrosion processes of magnesium-based biodegradable implants for osteosynthesis, the other dedicated to the assessment of neuropathy in human gastroenteric dysmotility. The aimed endpoint was to develop pipelines, from image acquisition all the way to data quantification, that could be used by other research groups with similar questions and may inspire future interdisciplinary collaborations between medicine, natural science and engineering.In the first line of work, we have attempted to employ synchrotron-radiation micro-computed tomography (µCT) coupled with in situ loading tests to assess the mechanical properties of the bone-implant interface (Paper I). We have revealed the crucial importance of the radiation dose deposited on the sample, and that the mechanical loading geometry should be accurately determined in the planning steps of the experiment. Moving away from the mechanical testing, we have also explored a novel three-dimensional analysis of the corrosion by-products of biodegradable implants by combining x-ray µCT, neutron µCT and x-ray fluorescence mapping (Papers IV and V). The second line of work has assessed the potential of x-ray phase-contrast µCT and nano-resolution holotomography as ways to perform virtual histology of unstained peripheral and autonomic neural tissue. In full-thickness biopsies of the myenteric nervous system, qualitative and potentially quantitative differences have been shown between controls and patients affected by gastrointestinal dysmotility (Paper II). In unstained skin biopsies, the methods have failed to visualise peripheral nerves, but we could identify structural changes in the connective tissue of some patients when compared to controls and other patients (Paper III)

Improved resolution in x-ray tomography by super-resolution

In this paper, super-resolution imaging is described and evaluated for x-ray tomography and is compared with standard tomography and upscaling during reconstruction. Blurring is minimized due to the negligible point spread of photon counting detectors and an electromagnetically movable micro-focus x-ray spot. Scans are acquired in high and lowmagnification geometry, where the latter is used to minimize penumbral blurring fromthe x-ray source. Sharpness and level ofdetail can be significantly increased in reconstructed slices to the point where the source size becomes the limiting factor. The achieved resolution of the different methods is quantified and compared using biological samples via the edge spread function, modulation transfer function, and Fourier ring correlation

A load frame for in situ tomography at PETRA III

A load frame for in situ mechanical testing is developed for the microtomography end stations at the imaging beamline P05 and the high-energy material science beamline P07 of PETRA III at DESY, both operated by the Helmholtz- Zentrum Geesthacht. The load frame is fully integrated into the beamline control system and can be controlled via a feedback loop. All relevant parameters (load, displacement, temperature, etc.) are continuously logged. It can be operated in compression or tensile mode applying forces of up to 1 kN and is compatible with all contrast modalities available at IBL and HEMS i.e. conventional attenuation contrast, propagation based phase contrast and differential phase contrast using a grating interferometer. The modularity and flexibility of the load frame allows conducting a wide range of experiments. E.g. compression tests to understand the failure mechanisms in biodegradable implants in rat bone or to investigate the mechanics and kinematics of the tessellated cartilage skeleton of sharks and rays, or tensile tests to illuminate the structure-property relationship in poplar tension wood or to visualize the 3D deformation of the tendonbone insertion. We present recent results from the experiments described including machine-learning driven volume segmentation and digital volume correlation of load tomography sequences