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A wide range of disorders are associated with alterations of the central and peripheral vascular system. Modified vascular corrosion casting using a newly developed polymer, allows for the first time hierarchical assessment of 3D vessel data in animals down to the level of capillaries. Imaging of large volumes of vasculature at intermediate resolution (16 µm) was performed using a desktop micro-computed tomography system. Subsequently regions of interest were identified for additional high resolution imaging (1.4 µm) at the X-ray Tomographic Microscopy (XTM) station of the Swiss Light Source (SLS). A framework for systematic hierarchical imaging and quantification was developed. Issues addressed included enhanced XTM data acquisition, introduction of local tomography, sample navigation, advanced post processing, and data combination. In addition to visual assessment of qualitative changes, morphometrical and architectural indices were determined using direct 3D morphometry software developed in house. Vessel specific parameters included thickness, surface, connectivity, and vessel length. Reconstructions of cerebral vasculature in mutant mice modeling Alzheimer's disease revealed significant changes in vessel architecture and morphology. In the future, a combination of these techniques may support drug discovery. Additionally, future ultra-high-resolution in vivo systems may even allow non-invasive tracking of temporal alterations in vascular morphology.