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)
- Light: Science & Applications Vol. 14, Issue 11, Pages: 3641-3652(2025)
- 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
  CLC：
- Received：16 March 2025，
  
  Revised：2025-07-29，
  
  Accepted：07 August 2025，
  
  Published Online：25 September 2025，
  
  Published：30 November 2025
- Accepted：
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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：

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.

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references

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