From Corrosion Casting to Virtual Dissection: Contrast‐Enhanced Vascular Imaging using Hafnium Oxide Nanocrystals

Abstract

Vascular corrosion casting is a method used to visualize the three dimensional (3D) anatomy and branching pattern of blood vessels. A polymer resin is injected in the vascular system and, after curing, the surrounding tissue is removed. The latter often deforms or even fractures the fragile cast. Here, a method is proposed that does not require corrosion, and is based on in situ micro computed tomography (micro‐CT) scans. To overcome the lack of CT contrast between the polymer cast and the animals' surrounding soft tissue, hafnium oxide nanocrystals (HfO2 NCs) are introduced 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. Careful design of the NC surface chemistry ensures the colloidal stability of the NCs in the casting resin. Using only 5 m% of HfO2 NCs, high‐quality cardiovascular casts of both zebrafish and mice can be automatically segmented using CT imaging software. This allows to differentiate even m‐scale details without having to alter the current resin injection methods. This new method of virtual dissection by visualizing casts in situ using contrast‐enhanced CT imaging greatly expands the application potential of the technique.

From Gel to Crystal: Mechanism of HfO2 and ZrO2 Nanocrystal Synthesis in Benzyl Alcohol

“…The HfO 2 nanocrystal synthesis is based on the original solvothermal synthesis by Buha et al, which was adapted into a microwave-assisted synthesis by De Roo et al and recently upscaled . The microwave procedure was conducted using a CEM Discover SP with an autosampler operating at a frequency of 2.45 GHz.…”

“…Hafnium oxide nanocrystals are particularly interesting since they are relevant for memory devices, − as X-ray CT contrast agents, − for scintillators, ,, for catalysis, or for radiotherapy . While HfO 2 can be synthesized in benzyl alcohol from HfCl 4 in a pressure bomb (autoclave), the reaction can also be performed in a microwave reactor, considerably shortening the reaction time to 3–4 h .…”

“…While HfO 2 can be synthesized in benzyl alcohol from HfCl 4 in a pressure bomb (autoclave), the reaction can also be performed in a microwave reactor, considerably shortening the reaction time to 3–4 h . We recently scaled up this reaction to deliver multiple grams of HfO 2 per batch . Key to the scale-up is the use of the highly soluble and less reactive HfCl 4 ·2THF complex, allowing for a high precursor concentration in benzyl alcohol.…”

Epitaxial Core/Shell Nanocrystals of (Europium-Doped) zirconia and hafnia

“…1 Colloidal ZrO2 NCs are components for (in)organic composites [2][3][4] while HfO2 NCs find applications in memory devices. 5,6 Due to the high atomic number of hafnium and the high density of hafnia, HfO2 NCs are developed as CT contrast agents, [7][8][9] scintillators, 10 and as radiation therapy enhancers. [11][12][13] Both ZrO2 and HfO2 NCs serve as hosts for optically active lanthanide ions, e.g, europium.…”

Epitaxial Core/Shell Nanocrystals of (Europium-Doped) Zirconia and Hafnia

“…Zirconium and hafnium oxide nanocrystals (NCs) are appealing (host) materials due to their high thermal and chemical stability and large band gap . Colloidal ZrO 2 NCs are components for (in)­organic composites, − while HfO 2 NCs find applications in memory devices. , Due to the high atomic number of hafnium and the high density of hafnia, HfO 2 NCs have been developed as computed tomography contrast agents, − scintillators, and radiation therapy enhancers. − …”