AbstractWe have demonstrated the capability of laboratory propagation-based microtomography (miroCT) in non-destructive 3D virtual histopathology of human blood clots without any contrast agent. The volumetric information are valuable to understand the mechanical properties of clots which are crucial in selecting the most efficient mechanical thrombectomy method for clot extraction. Different clot types retrieved by mechanical thrombectomy from patient victims of acute ischemic stroke were evaluated through propagation-based microCT. The results were correlated with high-resolution scanning electron microscopy (SEM) images, confirming detected cellular and fibrillary structures. Calcifications appeared as glassy opacity areas with relatively intense signal on microCT images, also proved by energy-dispersive spectroscopy and X-ray diffraction. Hyperintense regions on the microCT corresponded to individual or compact aggregates of red blood cells, whereas fibrin dominated volumes appeared at consistently moderate to low normalized microCT values. Red blood cell shapes and sizes are consistent with the SEM observations. Together with other potential parameters, 3D porosity distribution and volume fraction of structures can be easily measured by microCT data. Further development of automated post-processing techniques for X-ray propagation-based micro/nanoCT, also based on machine learning algorithms, can enable high throughput analysis of blood clot composition and their 3D histological features on large sample cohorts.