Nondestructive X-ray tomography of brain tissue ultrastructure
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Carles Bosch Pinol Tomas Aidukas Mirko Holler Alexandra Pacureanu Elisabeth Müller Chris Peddie Yuxin Zhang Phil Cook Lucy Collinson Oliver Bunk Andreas Menzel Manuel Guizar-Sicairos Gabriel Aeppli Ana Diaz Adrian A Wanner Andreas SchaeferAbstract
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 × 10¹⁰ 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.
Journal details
Journal
Nature Methods
Volume
22
Issue number
12
Pages
2631-2638
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10.1038/s41592-025-02891-0
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Europe PubMed Central
41310056
Pubmed
41310056
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The publication was previously a preprint.
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