From corrosion casting to virtual dissection: contrast-enhanced vascular imaging using hafnium oxide nanocrystals

Vascular corrosion casting is a method used to visualize the three dimensional anatomy and branching pattern of blood vessels, guiding insight into health and cardiovascular disease pathogenesis and progression. A polymer resin is injected in the vascular system and, after curing, the surrounding tissue is removed. This corrosion process often deforms or even fractures the fragile cast, resulting in an overall loss of information. Here, we propose a method that does not require corrosion of the tissue, based on in-situ high-resolution computed tomography (micro-CT) scans. Since there is a lack of CT contrast between the polymer cast and the animals’ surrounding soft tissue, we introduce hafnium oxide nanocrystals (HfO2 NCs) as CT contrast agents into the resin. The NCs dramatically improve the overall CT contrast of the cast and allow for straightforward segmentation in the CT scans. We designed the NC surface chemistry to ensure colloidal stability of the NCs in the casting resin, resulting in a homogeneous dispersion that remains stable during casting and curing. Using only 5 m% of HfO2 NCs, high-quality casts of both zebrafish and mouse models could be segmented using CT imaging software, allowing us to differentiate even μm scale details, without having to alter the resin injection method or affecting the resin’s mechanical properties. Our new method of virtual dissection by visualizing casts in-situ using contrast enhanced CT imaging greatly expands the application potential of the technique.