Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)

Zhenyue Chen; Yi Chen; Irmak Gezginer; Qingxiang Ding; Hikari A. I. Yoshihara; Xosé Luís Deán-Ben; Ruiqing Ni; Daniel Razansky

doi:10.1038/s41377-025-02003-9

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Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)

Original Articles

- Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)
- Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)
- Light: Science & Applications 2025年14卷第11期页码：3641-3652
- Affiliations：
  
  1.Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, China
  2.Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland
  3.Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland
  4.Zurich Neuroscience Center (ZNZ), Zurich, Switzerland
  5.Department of Nuclear Medicine, Inselspital, Bern, Switzerland
- Author bio：
  
  Daniel Razansky (daniel.razansky@uzh.ch)
- Funds：
- DOI：10.1038/s41377-025-02003-9
  中图分类号：
- 收稿：2025-03-16，
  
  修回：2025-07-29，
  
  录用：2025-08-07，
  
  网络出版：2025-09-25，
  
  纸质出版：2025-11-30
- Accepted：
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Zhenyue Chen, Yi Chen, Irmak Gezginer, 等. Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)[J]. Light: Science & Applications, 2025,14(11):3641-3652.

Chen, Z. et al. Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI). Light: Science & Applications, 14, 3641-3652 (2025).
Zhenyue Chen, Yi Chen, Irmak Gezginer, 等. Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)[J]. Light: Science & Applications, 2025,14(11):3641-3652. DOI： 10.1038/s41377-025-02003-9.

Chen, Z. et al. Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI). Light: Science & Applications, 14, 3641-3652 (2025). DOI： 10.1038/s41377-025-02003-9.

摘要

Abstract

A critical gap currently exists in systematic understanding and experimental validation of the role of astrocytes in neurovascular coupling and their functional links with other brain cells. Despite a broad selection of functional neuroimaging tools for multi-scale brain interrogations

no methodology currently exists that can discern responses from neural and glial cells while simultaneously mapping the associated hemodynamic activity on a large scale. We present a hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI) platform for measuring neuronal and astrocytic activity registered to concurrently recorded brain-wide hemodynamic responses. It features a fiberscope-based imaging system for multichannel fluorescence and optical intrinsic signal recordings and a custom surface radiofrequency coil

which are incorporated into the bore of a preclinical magnetic resonance imaging (MRI) scanner. We used HyFMRI to study peripheral-stimulus-evoked brain responses in mice differentially labeled with RCaMP and GCaMP genetically-encoded calcium indicators. Stimulation-evoked neuronal responses displayed the fastest kinetics and highest activation amplitude followed by astrocytic signals and the hemodynamic responses simultaneously recorded with functional MRI. In addition

the activation traces from neurons and astrocytes exhibited high linear correlation

thus providing direct evidence of astrocytic mediation in neurovascular coupling. This newly developed capacity to capture cell-type-specific calcium signaling alongside whole-brain hemodynamics enables the simultaneous investigation of neuro-glial-vascular interactions in health and disease. HyFMRI thus expands the current neuroimaging toolbox for a wide range of studies into synaptic plasticity

neural circuitry

brain function and disorders.

关键词

Keywords

references

Bonvento, G. & Bolaños, J. P. Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab. 33 , 1546–1564 (2021)..

Chen, Z. Y. et al. Multimodal optoacoustic imaging: methods and contrast materials. Chem. Soc. Rev. 53 , 6068–6099 (2024)..

Akerboom, J. et al. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front. Mol. Neurosci. 6 , 2 (2013)..

Stobart, J. L. et al. Cortical circuit activity evokes rapid astrocyte calcium signals on a similar timescale to neurons. Neuron 98 , 726–735. e4 (2018)..

Grienberger, C. & Konnerth , A. Imaging calcium in neurons. Neuron 73 , 862–885 (2012)..

Semyanov, A., Henneberger, C. & Agarwal, A. Making sense of astrocytic calcium signals—from acquisition to interpretation. Nat. Rev. Neurosci. 21 , 551–564 (2020)..

Bojarskaite, L. et al. Astrocytic Ca 2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep. Nat. Commun. 11 , 3240 (2020)..

Chen, Z. Y. et al. Hybrid magnetic resonance and optoacoustic tomography (MROT) for preclinical neuroimaging. Light Sci. Appl. 11 , 332 (2022)..

Chen, Z. Y.et al. Simultaneous functional magnetic resonance and optoacoustic imaging of brain-wide sensory responses in mice. Adv. Sci. 10 , 2205191 (2023)..

Ni, R. Q. et al. Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice. Nat. Biomed. Eng. 6 , 1031–1044 (2022)..

Chen, Z. Y. et al. Multimodal noninvasive functional neurophotonic imaging of murine brain-wide sensory responses. Adv. Sci. 9 , 2105588 (2022)..

Gezginer, I. et al. Concurrent optoacoustic tomography and magnetic resonance imaging of resting-state functional connectivity in the mouse brain. Nat. Commun. 15 , 10791 (2024)..

Schulz, K. et al. Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex. Nat. Methods 9 , 597–602 (2012)..

Schlegel, F. et al. Fiber-optic implant for simultaneous fluorescencebased calcium recordings and BOLD fMRI in mice. Nat. Protoc. 13 , 840–855 (2018)..

Zhou, Q. Y. et al. Cortex-wide transcranial localization microscopy with fluorescently labeled red blood cells. Nat. Commun. 15 , 3526 (2024)..

Chen, Z. Y. et al. Transcranial cortex-wide imaging of murine ischemic perfusion with large-field multifocal illumination microscopy. Stroke 56 , 170–182 (2025)..

Glück, C. et al. Pia-FLOW: deciphering hemodynamic maps of the pial vascular connectome and its response to arterial occlusion. Proc. Natl Acad. Sci. USA 121 , e2402624121 (2024)..

Chen, Z. Y. et al. High-speed large-field multifocal illumination fluorescence microscopy. Laser Photonics Rev. 14 , 1900070 (2020)..

Chen, L. M. et al. High-resolution maps of real and illusory tactile activation in primary somatosensory cortex in individual monkeys with functional magnetic resonance imaging and optical imaging. J. Neurosci. 27 , 9181–9191 (2007)..

Moon, C. H. et al. Neural interpretation of blood oxygenation level-dependent fMRI maps at submillimeter columnar resolution. J. Neurosci. 27 , 6892–6902 (2007)..

Lake, E. M. R. et al. Simultaneous cortex-wide fluorescence Ca 2+ imaging and whole-brain fMRI. Nat. Methods 17 , 1262–1271 (2020)..

Niskanen, J. P. AEDES at https://github.com/mjnissi/aedes.git https://github.com/mjnissi/aedes.git (2025).

Garrett, D. D. et al. Moment-to-moment brain signal variability: a next frontier in human brain mapping?. Neurosci. Biobehav. Rev. 37 , 610–624 (2013)..

Bran debura, A. N. et al. Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders. Nat. Rev. Neurosci. 24 , 23–39 (2023)..

Tesler, F., Linne, M. L. & Destexhe, A. Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics. Sci. Rep. 13 , 6451 (2023)..

Pang, J. C. et al. Effects of astrocytic dynamics on spatiotemporal hemodynamics: modeling and enhanced data analysis. NeuroImage 147 , 994–1005 (2017)..

Cardin, J. A., Crair, M. C. & Higley, M. J. Mesoscopic imaging: shining a wide light on large-scale neural dynamics. Neuron 108 , 33–43 (2020)..

Pisano, F. et al. Depth-resolved fiber photometry with a single tapered optical fiber implant. Nat. Methods 16 , 1185–1192 (2019)..

Sych, Y. et al. High-density multi-fiber photometry for studying large-scale brain circuit dynamics. Nat. Methods 16 , 553–560 (2019)..

Lu, Z. et al. A practical guide to scanning light-field microscopy with digital adaptive optics. Nat. Protoc. 17 , 1953–1979 (2022)..

Chen, Z. Y. et al. Multifocal structured illumination optoacoustic microscopy. Light Sci. Appl. 9 , 152 (2020)..

Chen, Z. Y. et al. Widefield fluorescence localization microscopy for transcranial imaging of cortical perfusion with capillary resolution. Opt. Lett. 45 , 3470–3473 (2020)..

Zhou, Q. Y. et al. Three-dimensional wide-field fluorescence microscopy for transcranial mapping of cortical microcirculation. Nat. Commun. 13 , 7969 (2022)..

Qian, Y. et al. A genetically encoded near-infrared fluorescent calcium ion indicator. Nat. Methods 16 , 171–174 (2019)..

Shaykevich, S. F. et al. Multimodal fluorescence-optoacoustic in vivo imaging of the near-infrared calcium ion indicator NIR-GECO2G. Photoacoustics 41 , 100671 (2025)..

Wang, Q. X. et al. The Allen mouse brain common coordinate framework: a 3D reference atlas. Cell 181 , 936–953. e20 (2020)..

Yizhar, O. et al. Optogenetics in neural systems. Neuron 71 , 9–34 (2011)..

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