Dose-efficient scanning Compton X-ray microscopy

Li, Tang; Dresselhaus, J.; Ivanov, N. G.; Prasciolu, Mauro; Fleckenstein, H.; Yefanov, Oleksandr; Zhang, Wenhui; Pennicard, David; Dippel, Ann Christin; Gutowski, Olof; Villanueva-Pérez, P.; Chapman, Henry N.; Bajt, Saša

doi:10.1038/s41377-023-01176-5

Cited by 5 publications

(1 citation statement)

References 37 publications

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“…As discussed previously (Holler et al ., 2017a), we expect significant improvements with the advent of fourth generation synchrotrons which will benefit from 1-2 orders of magnitude increased coherent X-ray flux (Yabashi and Tanaka, 2017). Furthermore, improvements in X-ray optics, such as replacing monochromators with multilayer mirrors (Bilderback et al, 1983) and Fresnel zone plates with Kirkpatrick-Baetz mirrors (Kirkpatrick and Baez, 1948; Morawe et al, 2015) or multilayer Laue lenses (Bajt et al, 2018; Li et al, 2023; Murray et al, 2019) can increase coherent flux by another 30-100 fold. Together with improved beam stability and improved detection systems that can maximally utilise increased flux, the upcoming innovations have the potential to improve overall acquisition speed by more than 4 orders of magnitude, putting non-destructive synaptic resolution imaging of cubic millimetre volumes well into the realm of standard beamtimes (Du et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Non-destructive X-ray tomography of brain tissue ultrastructure

Bosch,

Aidukas,

Holler

et al. 2023

Preprint

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Wiring diagrams of neural circuits are of central importance in delineating mechanisms of computation in the brain (Lichtman and Sanes, 2008; Litwin-Kumar and Turaga, 2019). To generate these diagrams, the individual parts of neurons - axons, dendrites and synapses - must be densely identified in 3-dimensional volumes of neuronal tissue. This is typically achieved by electron microscopy (Kornfeld and Denk, 2018), necessitating physical sectioning of the specimen either before or during the image acquisition process using ultrathin sectioning techniques or gallium or gas cluster ion beams (Denk and Horstmann, 2004; Hayworth et al., 2020; Kasthuri et al., 2015; Xu et al., 2017). Here, we demonstrate that X-ray ptychography (Pfeiffer, 2018), a coherent diffractive X-ray imaging technique, can faithfully acquire 3-dimensional images of metal-stained mouse neuronal tissue. Achieving high imaging quality requires minimization of the radiation damage to the sample, which we achieve by imaging at cryogenic temperatures and using specialised tomographic reconstruction algorithms (Odstrcil et al., 2019b). Using a newly identified tri-functional epoxy resin we demonstrate radiation resistance to X-ray doses exceeding 1011Gy. Sub-40 nm resolution makes it possible to densely resolve axon bundles, boutons, dendrites, and synapses without physical sectioning. Moreover, the tissue volumes can subsequently be imaged in 3D using high-resolution focused ion beam scanning electron microscopy (FIB-SEM) (Heymann et al., 2006; Knott et al., 2008) showing intact ultrastructure, suggesting that metal-stained neuronal tissue can be highly radiation-stable. Ongoing improvements in synchrotron, X-ray and detector physics (Yabashi and Tanaka, 2017), as well as further optimization of sample preparation and staining procedures (Hua et al., 2015; Karlupia et al., 2023; Lu et al., 2023; Mikula and Denk, 2015; Pallotto et al., 2015; Song et al., 2022), could lead to substantial improvements in acquisition speed (Du et al., 2021), whilst widening the volumes that can be imaged with X-ray techniques using laminography (Helfen et al., 2005; Helfen et al., 2013; Holler et al., 2020b; Holler et al., 2019) and nano-holotomography (Cloetens et al., 1999; Kuan et al., 2020) could allow for non-destructive X-ray imaging of synapses and neural circuits contained in volumes of increasing size.

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