Nondestructive X-ray tomography of brain tissue ultrastructure.

Bosch, Carles; Aidukas, Tomas; Holler, Mirko; Pacureanu, Alexandra; Müller, Elisabeth; Peddie, Christopher J; Zhang, Yuxin; Cook, Phil et al. · Nat Methods · 2025

basic_science · Level V

Where this comes from

Abstract

Maps of biological tissues at subcellular detail are key for understanding how organs function. X-ray nanotomography is a promising alternative to volume electron microscopy: it has the potential to nondestructively image millimeter-sized samples at ultrastructural resolution within a few days. A fundamental barrier is that the intense X-rays required for imaging also deform and disintegrate the tissue samples. Here we show a combination of solutions that overcome this barrier: We used a cryogenic and stable sample stage, tailored nonrigid tomographic reconstruction algorithms and an epoxy resin developed for the nuclear and aerospace industry. Tissue samples were resistant to radiation doses exceeding 1.15 × 10<sup>10</sup> Gy, and sub-40 nm isotropic resolution allowed identifying axon bundles, dendrites and synapses in mouse brain tissue without physical sectioning. Using volume electron microscopy, we demonstrate that tissue ultrastructure remains intact after X-ray imaging. Together, this unlocks the potential of X-ray tomography for high-resolution tissue imaging.

Medical subject headings