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In vivo imaging of central nervous system fluid spaces using synchrotron radiation-based micro computed tomography.

Overview

Authors: Marta Girona Alarcón1, Willy Kuo1, Mattia Humbel2, Christine Tanner2, Luca Fardin3, Britta Bausch1, Yann Decker4, Irene Spera5,6, Griffin Rodgers7, Hans Deyhle2, Alberto Bravin8,9, Masato Hoshino10, Arash Panahifar11,12, Kentaro Uesugi10, Sergei Gasilov13, Petr Pleskač5, Yuansheng Zhang1, Diane de Zélicourt1, Amandine Brenna5, Ahmad Kamal Hamid14, Pooya Razzaghi Khamesi1, Britta Engelhardt5, Steven T Proulx5, Bert Müller2, Vartan Kurtcuoglu1,15,16
ORCID iDs: Marta Girona Alarcón, Willy Kuo, Mattia Humbel, Irene Spera, Alberto Bravin, Masato Hoshino, Amandine Brenna, Ahmad Kamal Hamid, Britta Engelhardt, Steven T Proulx, Bert Müller, Vartan Kurtcuoglu
16 affiliations
  1. University of Zurich, Department of Physiology, The Interface Group, Zurich, Switzerland
  2. University of Basel, Department of Biomedical Engineering, Biomaterials Science Center, Allschwil, Switzerland
  3. Elettra Sincrotrone Trieste, Trieste, Italy
  4. Saarland University Medical Center, Department of Neurology, Homburg, Germany
  5. Theodor Kocher Institute, University of Bern, Bern, Switzerland
  6. University of Basel, Department of Biomedicine, Basel, Switzerland
  7. Paul Scherrer Institute, Center for Photon Science, Laboratory for Macromolecules and Bioimaging, Villigen, Switzerland
  8. University of Milano-Bicocca, Department of Physics, Milano, Italy
  9. University of Calabria, Department of Physics, Arcavacata di Rende, Cosenza, Italy
  10. Japan Synchrotron Radiation Research Institute, Spectroscopy and Imaging Division, Sayo, Japan
  11. Canadian Light Source, Biomedical Imaging and Therapy Beamline, Saskatoon, Canada
  12. University of Saskatchewan, College of Medicine, Department of Medical Imaging, Saskatoon, Canada
  13. Helmholtz-Zentrum Hereon, Institute of Material Physics, Hamburg, Germany
  14. Broad Institute of MIT and Harvard, Imaging Platform, Cambridge, Massachusetts USA
  15. University of Zurich, Neuroscience Center Zurich, Zurich, Switzerland
  16. University of Zurich, Zurich Center for Integrative Human Physiology, Zurich, Switzerland
Institutions: University of Zurich (Switzerland); University of Basel (Switzerland); Elettra-Sincrotrone Trieste S.C.p.A. (Italy); Universitätsklinikum des Saarlandes (Germany); Saarland University (Germany); University of Bern (Switzerland); Paul Scherrer Institute (Switzerland); University of Calabria (Italy); University of Milano-Bicocca (Italy); Japan Synchrotron Radiation Research Institute (Japan); University of Saskatchewan (Canada); Canadian Light Source (Canada) (Canada); Helmholtz-Zentrum Hereon (Germany); Broad Institute (United States)
Journal: Nature communications, volume 17, issue 1, article 5959
Dates: received 21 January 2026; accepted 27 March 2026; published online 2 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-71835-9 · PMID 42069697 · PMCID PMC13342594 · OpenAlex W4415343851
Open access: gold, a free copy (OpenAlex)
Preprint: arxiv:2507.03186
Status: data only
Categories: other (modality), histology / microscopy (modality), mouse (organism), methods / tools (subfield)
Methods: Machine learning, Connectivity, fMRI & imaging, Smoothing, state filtering, decompositions, Evoked potentials, Physiology & signal measures
Keywords: Brain, Databases
MeSH: Brain*, Central Nervous System*, Cerebrospinal Fluid*, Synchrotrons*, X-Ray Microtomography*, Animals, Intravital Microscopy, Male, Mice, Mice, Inbred C57BL (* major topic)
Topic: Medical Imaging Techniques and Applications (Radiology, Nuclear Medicine and Imaging, Medicine), according to OpenAlex
Funding: Swiss National Science Foundation (189226, SNSF Sinergia CRSII5_213535, 310030, SNSF Project 310030_189226, 213535)
Citations: cited by 1 paper (Europe PMC); 101 references in the paper

Abstract

Current intravital imaging techniques for the mouse central nervous system (CNS) do not simultaneously provide micrometer-scale spatial resolution, whole-brain coverage, and sub-minute temporal resolution, limiting organ-wide interrogation of CNS fluid dynamics in vivo. Here, we introduce intravital synchrotron radiation-based hard X-ray micro computed tomography (SRµCT), a modality that enables dynamic whole-brain imaging at micrometer-scale spatial resolution in living mice. We performed intravital SRµCT of mouse CNS fluid spaces at three synchrotron radiation facilities, imaging both anesthetized free-breathing and mechanically ventilated animals, with and without retrospective cardiac gating. This approach achieves complete brain coverage with temporal resolution of up to 23 s and voxel sizes down to 6.3 µm, at an effective spatial resolution better than 20 µm, enabling time-resolved visualization of cerebrospinal fluid (CSF) contrast distribution and quantitative analysis of tissue motion across the entire brain. By combining micrometer-scale resolution, whole-organ field of view, and dynamic intravital imaging, SRµCT closes a long-standing methodological gap between optical microscopy and magnetic resonance imaging. Intravital SRµCT provides access to spatiotemporal information that cannot be obtained with existing techniques and establishes a framework for testing and integrating mechanistic models of CSF dynamics and solute transport at the scale of the whole brain.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Code availability

All original code has been deposited at Zenodo54 under GNU General Public License v3.0 or later and is publicly available as of the date of publication. The repository includes Python scripts for calculating Fourier shell correlation (FSC) and Fourier ring correlation (FRC), MATLAB and elastix code for image registration, Python code using scikit-image along with Amira project files for image segmentation, and Python code using PyVista to generate meshes from the segmentations. It also includes MATLAB code for retrospective cardiac gating, LabVIEW code for animal monitoring equipment, Arduino code for ventilator synchronization, as well as Nabu scripts and Python code using TomoPy for tomographic reconstruction.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

The reconstructed 3D SRµCT data generated in this study have been deposited under a Creative Commons Attribution 4.0 International license in the Zenodo repository under 10.5281/zenodo.15684790, 10.5281/zenodo.15674822, 10.5281/zenodo.15674076, 10.5281/zenodo.15676994, 10.5281/zenodo.15682921, 10.5281/zenodo.15671325, 10.5281/zenodo.15671360, 10.5281/zenodo.15675683, 10.5281/zenodo.15677930, and 10.5281/zenodo.15690358, linked through the main Zenodo deposition 10.5281/zenodo.1377308054. For time series experiments, a single reconstructed 2D section is provided for each time point. Full 3D stacks are included for only one or two representative time points due to their cumulative size of 2.7 terabytes. The remaining datasets reported in this paper will be shared by the corresponding author upon request. Computer-aided design (CAD) files of the mouse holder, infusion cannula, intra-cisterna magna infusion, and tracheotomy stage, along with extended metadata and quantitative results tables, have been also deposited at the main Zenodo repository 10.5281/zenodo.13773080. Information on other available datasets can be accessed via the FABRIC4 portal77.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 25 authors, 2 keywords, 10 MeSH terms, 1 funder, 91 references.

Cite

This paper

Girona Alarcón, M., Kuo, W., Humbel, M., Tanner, C., Fardin, L., Bausch, B., Decker, Y., Spera, I., Rodgers, G., Deyhle, H., Bravin, A., Hoshino, M., Panahifar, A., Uesugi, K., Gasilov, S., Pleskač, P., Zhang, Y., de Zélicourt, D., Brenna, A., . . . Kurtcuoglu, V. (2026). In vivo imaging of central nervous system fluid spaces using synchrotron radiation-based micro computed tomography. Nature communications, 17(1), 5959. https://doi.org/10.1038/s41467-026-71835-9

BibTeX

@article{gironaalarcon2026vivo,
author = {Girona Alarcón, Marta and Kuo, Willy and Humbel, Mattia and Tanner, Christine and Fardin, Luca and Bausch, Britta and Decker, Yann and Spera, Irene and Rodgers, Griffin and Deyhle, Hans and Bravin, Alberto and Hoshino, Masato and Panahifar, Arash and Uesugi, Kentaro and Gasilov, Sergei and Pleskač, Petr and Zhang, Yuansheng and de Zélicourt, Diane and Brenna, Amandine and Hamid, Ahmad Kamal and Razzaghi Khamesi, Pooya and Engelhardt, Britta and Proulx, Steven T and Müller, Bert and Kurtcuoglu, Vartan},
title = {{In vivo imaging of central nervous system fluid spaces using synchrotron radiation-based micro computed tomography}},
journal = {Nature communications},
year = {2026},
month = may,
volume = {17},
number = {1},
pages = {5959},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-71835-9},
url = {https://doi.org/10.1038/s41467-026-71835-9},
pmid = {42069697},
pmcid = {PMC13342594}
}

RIS

TY - JOUR
AU - Girona Alarcón, Marta
AU - Kuo, Willy
AU - Humbel, Mattia
AU - Tanner, Christine
AU - Fardin, Luca
AU - Bausch, Britta
AU - Decker, Yann
AU - Spera, Irene
AU - Rodgers, Griffin
AU - Deyhle, Hans
AU - Bravin, Alberto
AU - Hoshino, Masato
AU - Panahifar, Arash
AU - Uesugi, Kentaro
AU - Gasilov, Sergei
AU - Pleskač, Petr
AU - Zhang, Yuansheng
AU - de Zélicourt, Diane
AU - Brenna, Amandine
AU - Hamid, Ahmad Kamal
AU - Razzaghi Khamesi, Pooya
AU - Engelhardt, Britta
AU - Proulx, Steven T
AU - Müller, Bert
AU - Kurtcuoglu, Vartan
TI - In vivo imaging of central nervous system fluid spaces using synchrotron radiation-based micro computed tomography
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/05/02
VL - 17
IS - 1
SP - 5959
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-71835-9
UR - https://doi.org/10.1038/s41467-026-71835-9
LA - en
ER -

CSL-JSON

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