OSCR

Double-helix optical point spread function enables real-time mesoscopic 3D functional microangiography in the living mouse brain and skull.

Overview

Authors: Baoyuan Zhang1,2,3, Shiyao Guo4, Lin Tang1,2, Yi Chen1,2, Lukas Glandorf1,2, Etienne Jessen5, Xuyang Chang1,2, Tian Jin1,2, Michael Reiss1,2, Shuxin Lyu1,2, Qiang Fu6, Hadi Amata6, Wolfgang Heidrich6, Chaim Glück1, Dominik Schillinger5, Bruno Weber1, Xosé Luís Deán-Ben1,2, Weibo Wang3, Xiong Dun4, Daniel Razansky1,2, Zhenyue Chen4, Quanyu Zhou1,2
ORCID iDs: Baoyuan Zhang, Lin Tang, Yi Chen, Lukas Glandorf, Etienne Jessen, Xuyang Chang, Michael Reiss, Qiang Fu, Hadi Amata, Wolfgang Heidrich, Chaim Glück, Bruno Weber, Xosé Luís Deán-Ben, Daniel Razansky, Zhenyue Chen, Quanyu Zhou
  1. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
  2. Institute for Biomedical Engineering, ETH Zurich and University of Zurich, Zurich, Switzerland
  3. Center of Ultra-Precision Optoelectronic Instrument Engineering, Harbin Institute of Technology, Harbin, China
  4. School of Physics Science and Engineering, Tongji University, Shanghai, China
  5. Institute for Mechanics, Computational Mechanics Group, Technical University of Darmstadt, Darmstadt, Germany
  6. King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
Institutions: University of Zurich (Switzerland); Harbin Institute of Technology (China); ETH Zurich (Switzerland); Institute for Biomedical Engineering (Switzerland); Tongji University (China); Technische Universität Darmstadt (Germany); King Abdullah University of Science and Technology (Saudi Arabia)
Journal: Nature communications, volume 17, issue 1, article 5167
Dates: received 23 September 2025; accepted 27 March 2026; published online 13 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-71746-9 · PMID 41974741 · PMCID PMC13249855 · OpenAlex W7154059155
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: histology / microscopy (modality), mouse (organism), other condition (population), stroke (population)
Methods: Machine learning, Statistics, fMRI & imaging, Physiology & signal measures
Keywords: Imaging and sensing, Fluorescence imaging
MeSH: Angiography*, Brain*, Imaging, Three-Dimensional*, Skull*, Animals, Cerebrovascular Circulation, Glioma, Male, Mice, Microcirculation, Microscopy, Confocal, Optical Imaging (* major topic)
Topic: Advanced Fluorescence Microscopy Techniques (Biophysics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Swiss National Science Foundation (10.006.824, 10.003.762)
Citations: cited by 1 paper (Europe PMC); 69 references in the paper

Abstract

Quantitative, volumetric imaging of cerebrovascular networks and microcirculation is essential for understanding brain function. However, rapid mesoscopic 3D imaging remains challenging because of fundamental trade-offs between spatiotemporal resolution, field of view, and sensitivity to functional parameters. Here we present a mesoscopic fluorescence imaging platform featuring a double-helix phase mask for real-time, depth-resolved measurements through the intact mouse skull. The compact phase-mask design is compatible with both laser-scanning and widefield microscopy. Using multifocal laser scanning, we demonstrate real-time volumetric in vivo imaging while discriminating calvarial from cerebral vasculature across 6.6×6.6×0.8 mm3 volume. Beyond high-resolution structural imaging, perfusion time-to-peak values are extracted from the laser-scanning configuration while accurate flow velocity/direction information is provided via widefield tracking of fluorescently labeled cells. We demonstrate the platform’s capabilities by analyzing brain-layer-specific perfusion dynamics and vascular topology in glioma-bearing mouse brains, offering unprecedented views for probing cerebrovascular alterations in both physiological and pathological contexts.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

Localization of fluorescence emitters was performed with the open-source TrackNTrace toolbox63. RBC tracking was performed using the SimpleTracker algorithm36. ADMM reconstruction was performed with the open-source DiffuserCam code69. Pseudocode outlining the main DH-PSF image reconstruction workflow is included in the Supplementary Information (Supplementary Algorithm 1). Custom MATLAB codes for data analysis which are available for research purposes from the corresponding author upon request.

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 (its code is available on request), so it has no map.

Data

Datasets cited

Data availability

The main data supporting the finding of this study are available within the main text or Supplementary Information. Representative raw imaging datasets supporting the findings of this study have been deposited in Zenodo and are publicly available at 10.5281/zenodo.18876905. Source data are provided with this paper.

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, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 22 authors, 2 keywords, 12 MeSH terms, 1 funder, 59 references.

Cite

This paper

Zhang, B., Guo, S., Tang, L., Chen, Y., Glandorf, L., Jessen, E., Chang, X., Jin, T., Reiss, M., Lyu, S., Fu, Q., Amata, H., Heidrich, W., Glück, C., Schillinger, D., Weber, B., Deán-Ben, X. L., Wang, W., Dun, X., . . . Zhou, Q. (2026). Double-helix optical point spread function enables real-time mesoscopic 3D functional microangiography in the living mouse brain and skull. Nature communications, 17(1), 5167. https://doi.org/10.1038/s41467-026-71746-9

BibTeX

@article{zhang2026double,
author = {Zhang, Baoyuan and Guo, Shiyao and Tang, Lin and Chen, Yi and Glandorf, Lukas and Jessen, Etienne and Chang, Xuyang and Jin, Tian and Reiss, Michael and Lyu, Shuxin and Fu, Qiang and Amata, Hadi and Heidrich, Wolfgang and Glück, Chaim and Schillinger, Dominik and Weber, Bruno and Deán-Ben, Xosé Luís and Wang, Weibo and Dun, Xiong and Razansky, Daniel and Chen, Zhenyue and Zhou, Quanyu},
title = {{Double-helix optical point spread function enables real-time mesoscopic 3D functional microangiography in the living mouse brain and skull}},
journal = {Nature communications},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {5167},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-71746-9},
url = {https://doi.org/10.1038/s41467-026-71746-9},
pmid = {41974741},
pmcid = {PMC13249855}
}

RIS

TY - JOUR
AU - Zhang, Baoyuan
AU - Guo, Shiyao
AU - Tang, Lin
AU - Chen, Yi
AU - Glandorf, Lukas
AU - Jessen, Etienne
AU - Chang, Xuyang
AU - Jin, Tian
AU - Reiss, Michael
AU - Lyu, Shuxin
AU - Fu, Qiang
AU - Amata, Hadi
AU - Heidrich, Wolfgang
AU - Glück, Chaim
AU - Schillinger, Dominik
AU - Weber, Bruno
AU - Deán-Ben, Xosé Luís
AU - Wang, Weibo
AU - Dun, Xiong
AU - Razansky, Daniel
AU - Chen, Zhenyue
AU - Zhou, Quanyu
TI - Double-helix optical point spread function enables real-time mesoscopic 3D functional microangiography in the living mouse brain and skull
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/04/13
VL - 17
IS - 1
SP - 5167
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-71746-9
UR - https://doi.org/10.1038/s41467-026-71746-9
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s41467-026-71746-9",
"type": "article-journal",
"title": "Double-helix optical point spread function enables real-time mesoscopic 3D functional microangiography in the living mouse brain and skull",
"container-title": "Nature communications",
"author": [
{
"family": "Zhang",
"given": "Baoyuan"
},
{
"family": "Guo",
"given": "Shiyao"
},
{
"family": "Tang",
"given": "Lin"
},
{
"family": "Chen",
"given": "Yi"
},
{
"family": "Glandorf",
"given": "Lukas"
},
{
"family": "Jessen",
"given": "Etienne"
},
{
"family": "Chang",
"given": "Xuyang"
},
{
"family": "Jin",
"given": "Tian"
},
{
"family": "Reiss",
"given": "Michael"
},
{
"family": "Lyu",
"given": "Shuxin"
},
{
"family": "Fu",
"given": "Qiang"
},
{
"family": "Amata",
"given": "Hadi"
},
{
"family": "Heidrich",
"given": "Wolfgang"
},
{
"family": "Glück",
"given": "Chaim"
},
{
"family": "Schillinger",
"given": "Dominik"
},
{
"family": "Weber",
"given": "Bruno"
},
{
"family": "Deán-Ben",
"given": "Xosé Luís"
},
{
"family": "Wang",
"given": "Weibo"
},
{
"family": "Dun",
"given": "Xiong"
},
{
"family": "Razansky",
"given": "Daniel"
},
{
"family": "Chen",
"given": "Zhenyue"
},
{
"family": "Zhou",
"given": "Quanyu"
}
],
"container-title-short": "Nat Commun",
"volume": "17",
"issue": "1",
"page": "5167",
"DOI": "10.1038/s41467-026-71746-9",
"PMID": "41974741",
"PMCID": "PMC13249855",
"ISSN": "2041-1723",
"publisher": "Nature Publishing Group",
"URL": "https://doi.org/10.1038/s41467-026-71746-9",
"language": "en",
"issued": {
"date-parts": [
[
2026,
4,
13
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41467-026-71742-z [code]
Hypercapnia dissociates neuronal and hemodynamic responses impairing neurovascular coupling and functional brain connectivity.
Journal: Nature communications
In common: mouse, 3 authors
[2] doi:10.1073/pnas.2513515123
ECgo: All-optical induction of single endothelial cell injury and capillary occlusion in the brain.
Journal: Proceedings of the National Academy of Sciences of the United States of America
In common: mouse, 2 authors
[3] doi:10.1038/s41593-026-02354-5 [code]
Focal astrocyte loss reveals nuclear translocation during lesion repopulation.
Journal: Nature neuroscience
In common: mouse, author Bruno Weber
[4] doi:10.1038/s41377-026-02252-2
Ultra-wide-field, deep, adaptive two-photon microscopy for multi-scale neuronal imaging.
Journal: Light, science & applications
In common: histology / microscopy, 3 references
[5] doi:10.1109/tmi.2026.3704144 [code]
Microbubble Track-Based Functional Ultrasound Localization Microscopy in Awake Mice.
Journal: IEEE transactions on medical imaging
In common: histology / microscopy, mouse, 2 references
[6] doi:10.1038/s41467-026-73045-9 [code]
Aberration-aware 3D localization microscopy via self-supervised neural-physics learning.
Journal: Nature communications
In common: histology / microscopy, 2 references
[7] doi:10.1038/s41467-026-72961-0 [code]
Real-time volumetric imaging of cells and molecules in deep tissues with Takoyaki ultrasound.
Journal: Nature communications
In common: other condition, mouse, 2 references
[8] doi:10.1038/s41467-026-74253-z
Disruption of the brain-spleen axis impairs monocyte-microglia communication and accelerates disease progression in a mouse model of amyloidosis.
Journal: Nature communications
In common: mouse, 2 references
[9] doi:10.1117/1.nph.13.2.025007
Inducing and monitoring photothrombotic stroke in anesthetic neuroprotection-free mice using functional photoacoustic microscopy.
Journal: Neurophotonics
In common: stroke, histology / microscopy, mouse, 1 reference
[10] doi:10.1371/journal.pone.0343516
NeuronID: An automatic toolkit for identifying neurons in two-photon calcium imaging data.
Journal: PloS one
In common: histology / microscopy, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.