Nondestructive X-ray tomography of brain tissue ultrastructure
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.
Authors
- Ana Díaz (ORCID: https://orcid.org/0000-0003-0479-4752)
- Tomas Aidukas
- Oliver Bunk (ORCID: https://orcid.org/0000-0001-6563-4053)
- Andreas T. Schaefer (ORCID: https://orcid.org/0000-0002-4677-8788)
- Adrian Wanner (ORCID: https://orcid.org/0000-0002-5864-8577)
- Phil Cook (ORCID: https://orcid.org/0000-0001-5714-4257)
- Andreas Menzel (ORCID: https://orcid.org/0000-0002-0489-609X)
- Lucy Collinson (ORCID: https://orcid.org/0000-0003-0260-613X)
- Christopher J. Peddie (ORCID: https://orcid.org/0000-0002-8329-5419)
- Mirko Holler (ORCID: https://orcid.org/0000-0001-8141-0148)
- Alexandra Pacureanu (ORCID: https://orcid.org/0000-0003-2306-7040)
- Meret Aeppli (ORCID: https://orcid.org/0000-0003-3335-3673)
- Carles Bosch (ORCID: https://orcid.org/0000-0003-4179-0451)
- E. Müller (ORCID: https://orcid.org/0000-0001-8239-7109)
- Manuel Guizar‐Sicairos (ORCID: https://orcid.org/0000-0002-8293-3634)
- Yuxin Zhang (ORCID: https://orcid.org/0000-0003-0243-2520)
Institutions
- Board of the Swiss Federal Institutes of Technology (CH)
- The Francis Crick Institute (GB)
- European Synchrotron Radiation Facility (FR)
- Paul Scherrer Institute (CH)
- University College London (GB)
- École Polytechnique Fédérale de Lausanne (CH)
Publication Details
- Journal
- Nature Methods
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1038/s41592-025-02891-0
- Citations
- 4
- Primary Topic
- Advanced X-ray Imaging Techniques
- Type
- article
- Field-Weighted Citation Impact
- 7.53