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Ultra-wide-field, deep, adaptive two-photon microscopy for multi-scale neuronal imaging.

Overview

Authors: Mengke Yang1,2, Zhen-Qiao Zhou1,3,4, Song Lang1,3,4, Hanqing Zheng1,3,4, Shuai Chen1,3,4,5, Tong Li6, Eline Stas2, Jess Yu2, Long Zhang1,3,4, Zhi Zhang1,3,4, Volkan Uzungil2, Qinying Liu1,3,4, Yu Huang1,3,4,5, Jing Lyu1,3,4, Yimei Li2, Hongbo Jia1,5,7,8, Min Li1,3,4, Xiaojing Li9, Jingwei Li9, Yuguo Tang1,3,4, Yan Gong1,3,4, Simon R. Schultz2
ORCID iDs: Jess Yu, Volkan Uzungil, Jing Lyu, Hongbo Jia, Min Li, Simon R. Schultz
  1. Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences,Suzhou, China
  2. Department of Bioengineering and Centre for Neurotechnology, Imperial College London,London, UK
  3. Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences,Suzhou, China
  4. State Key Laboratory of Biomedical Imaging Science and System, Suzhou, China
  5. School of Physics and Engineering, Guangxi University,Guangxi, China
  6. State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University,Beijing, China
  7. Leibniz Institute for Neurobiology (LIN),Magdeburg, Germany
  8. Institute of Neuroscience and the Synergy Cluster, Technical University of Munich,Munich, Germany
  9. Department of Neurology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University,Suzhou, China
Institutions: Chinese Academy of Sciences (China); Imperial College London (United Kingdom); Guangxi University (China); Beijing Normal University (China); Leibniz Institute for Neurobiology (Germany); Technical University of Munich (Germany); Nanjing University (China)
Journal: Light, science & applications, volume 15, issue 1, article 198
Dates: received 9 October 2025; accepted 20 February 2026; published online 13 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41377-026-02252-2 · PMID 41974661 · PMCID PMC13077073 · OpenAlex W7154011970
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: histology / microscopy (modality), optical imaging (calcium, voltage, 2-photon) (modality)
Methods: Evoked potentials, Connectivity, Machine learning, fMRI & imaging, Single-unit activity, calcium imaging, Physiology & signal measures
Keywords: Biophotonics, Multiphoton microscopy
Topic: Advanced Fluorescence Microscopy Techniques (Biophysics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Engineering and Physical Sciences Research Council (EP/W024020/1, EP/Y020316/1); Science and Technology Support Program of Jiangsu Province (Jiangsu Province Science and Technology Support Program) (BM2022010); Youth Innovation Promotion Association of the Chinese Academy of Sciences (Youth Innovation Promotion Association CAS) (2022328); National Natural Science Foundation of China (National Science Foundation of China) (61705251)
Citations: cited by 2 papers (Europe PMC); 49 references in the paper

Abstract

Observing the activity patterns of large neural populations throughout the brain is essential for understanding brain function. However, capturing neural interactions across widely distributed brain regions from both superficial and deep cortical layers remains challenging with existing microscopy technologies. Here, we introduce a state-of-the-art two-photon microscopy system, ULTRA, capable of single-cell resolution imaging across an ultra-large field of view (FOV) exceeding 50 mm², enabling deep and wide field in vivo imaging. To demonstrate its capabilities, we conducted a series of experiments under multiple imaging conditions, successfully visualizing brain structures and neuronal activities spanning a spatial range of over 7 mm from superficial layers to depths of up to 900 μm, while covering a volume of 45.24 mm3 in the mouse brain. This versatile imaging platform overcomes traditional spatial constraints, providing a powerful tool for comprehensive exploration of neuronal circuitry over extensive spatial scales with cellular resolution.

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

Code

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Data

Datasets cited

Data availability

Data sufficient to reproduce figures in this paper is available via DataDryad (datadryad.org) at the address 10.5061/dryad.z612jm6s4. Raw imaging data from the studies reported here are available upon reasonable request from the corresponding author.

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, 4 funders, 48 references.

Cite

This paper

Yang, M., Zhou, Z.-Q., Lang, S., Zheng, H., Chen, S., Li, T., Stas, E., Yu, J., Zhang, L., Zhang, Z., Uzungil, V., Liu, Q., Huang, Y., Lyu, J., Li, Y., Jia, H., Li, M., Li, X., Li, J., . . . Schultz, S. R. (2026). Ultra-wide-field, deep, adaptive two-photon microscopy for multi-scale neuronal imaging. Light, science & applications, 15(1), 198. https://doi.org/10.1038/s41377-026-02252-2

BibTeX

@article{yang2026ultra,
author = {Yang, Mengke and Zhou, Zhen-Qiao and Lang, Song and Zheng, Hanqing and Chen, Shuai and Li, Tong and Stas, Eline and Yu, Jess and Zhang, Long and Zhang, Zhi and Uzungil, Volkan and Liu, Qinying and Huang, Yu and Lyu, Jing and Li, Yimei and Jia, Hongbo and Li, Min and Li, Xiaojing and Li, Jingwei and Tang, Yuguo and Gong, Yan and Schultz, Simon R.},
title = {{Ultra-wide-field, deep, adaptive two-photon microscopy for multi-scale neuronal imaging}},
journal = {Light, science \& applications},
year = {2026},
month = apr,
volume = {15},
number = {1},
pages = {198},
publisher = {Nature Publishing Group},
issn = {2095-5545},
doi = {10.1038/s41377-026-02252-2},
url = {https://doi.org/10.1038/s41377-026-02252-2},
pmid = {41974661},
pmcid = {PMC13077073}
}

RIS

TY - JOUR
AU - Yang, Mengke
AU - Zhou, Zhen-Qiao
AU - Lang, Song
AU - Zheng, Hanqing
AU - Chen, Shuai
AU - Li, Tong
AU - Stas, Eline
AU - Yu, Jess
AU - Zhang, Long
AU - Zhang, Zhi
AU - Uzungil, Volkan
AU - Liu, Qinying
AU - Huang, Yu
AU - Lyu, Jing
AU - Li, Yimei
AU - Jia, Hongbo
AU - Li, Min
AU - Li, Xiaojing
AU - Li, Jingwei
AU - Tang, Yuguo
AU - Gong, Yan
AU - Schultz, Simon R.
TI - Ultra-wide-field, deep, adaptive two-photon microscopy for multi-scale neuronal imaging
T2 - Light, science & applications
J2 - Light Sci Appl
PY - 2026
DA - 2026/04/13
VL - 15
IS - 1
SP - 198
SN - 2095-5545
PB - Nature Publishing Group
DO - 10.1038/s41377-026-02252-2
UR - https://doi.org/10.1038/s41377-026-02252-2
LA - en
ER -

CSL-JSON

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