The research describes a critical advancement in nondestructive X-ray nanotomography (PXCT) for imaging biological tissues at ultrastructural detail, offering a promising alternative to volume electron microscopy. The primary limitation of high-dose X-ray imaging-radiation-induced deformation and disintegration of soft tissue-was addressed through a combination of tailored solutions. Key components include utilizing a cryogenic sample stage, applying nonrigid reconstruction algorithms to computationally correct movement, and embedding samples in a novel, radiation-resistant epoxy resin (TGPAP-DDM). This robust protocol allowed samples to withstand doses exceeding 1 times 10^10 Gy, resulting in an isotropic resolution of sub-40 nm. This resolution is high enough to reliably identify fine neural features, such as axons, dendrites, and synapses, providing a scalable and intact method for 3D connectomics research.

References:

• Bosch C, Aidukas T, Holler M, et al. Nondestructive X-ray tomography of brain tissue ultrastructure[J]. Nature Methods, 2025: 1-8.