3D Virtual Histopathology by Multiscale X-Ray Phase-Contrast Tomography: Novel Tools and Applications

Histological analysis has been considered as the gold standard for studying tissue architecture for over two centuries, providing essential insights into tissue morphology and organization. However, the technique is inherently destructive and limited to the microscopic visualization of two-dimensional sections. In recent years, X-ray phase-contrast computed tomography (XPCT) has emerged as a promising non-destructive imaging modality which can bridge the gap between classical histology and volumetric imaging, enabling virtual 3D histology of intact tissues on multiple length scales. In this thesis, we explore the potential of XPCT as a tool for morphometric analysis and three-dimensional tissue characterization, with applications in neuroscience, pathology, and preclinical studies. The first section introduces the fundamentals of X-ray imaging, phase contrast formation and quantitative analysis. The second section investigates whether Neodymium acetate is suitable as a new staining agent for enhanced contrast in XPCT. In section three, XPCT is used to study a variety of neurodegenerative disease hallmarks in human brain tissue. The fourth section evaluates lung imaging, focusing on physiological and pathological features. In section five, whole-organ imaging of human placentae is addressed, with a focus on vasculature segmentation and three-dimensional tissue visualization across several length scales. Finally, section six demonstrates XPCT's scalability for laboratory, high-throughput imaging in preclinical models of SARS-CoV-2 infection in combination with morphometric tissue analysis. Combining advanced optics, phase retrieval algorithms, and morphometric analysis, this work establishes XPCT as a viable, non-destructive alternative to traditional histology, offering high-resolution 3D visualization of tissue morphology.