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Biphasic acclimation for simultaneous wide-field fluorescent Ca<sup>2+</sup> imaging and fMRI of awake mice.

Overview

Authors: Francesca Mandino1,2, Taekyung Kang3, Xilin Shen1, Corey Horien4, Xenophon Papademetris1,2,3,5,6, Stephen M Strittmatter6,7,8,9,10, Evelyn MR Lake1,2,3,6
ORCID iDs: Francesca Mandino, Taekyung Kang, Xenophon Papademetris
  1. Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
  2. Yale Biomedical Imaging Institute, Yale University, New Haven, CT, United States
  3. Department of Biomedical Engineering, Yale University, New Haven, CT, United States
  4. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States
  5. Department of Biomedical Informatics & Data Science, Yale University, New Haven, CT, United States
  6. Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, United States
  7. Cellular Neuroscience, Neurodegeneration and Repair Program, Yale School of Medicine, New Haven, CT, United States
  8. Department of Neurology, Yale University School of Medicine, New Haven, CT, United States
  9. Kavli Institute of Neuroscience, Yale University School of Medicine, New Haven, CT, United States
  10. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, United States
Institutions: Yale University (United States); University of Pennsylvania (United States)
Journal: Imaging neuroscience (Cambridge, Mass.), volume 4, article IMAG.a.1357
Dates: received 27 January 2026; accepted 7 August 2026; published online 10 September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1162/imag.a.1357 · PMID 42730032 · PMCID PMC13563530 · OpenAlex W7203444054
Open access: diamond, a free copy (OpenAlex)
Status: code on request
Categories: fMRI (modality), optical imaging (calcium, voltage, 2-photon) (modality), human (organism), mouse (organism)
Methods: Connectivity, Statistics, Preprocessing, fMRI & imaging, Physiology & signal measures
Keywords: awake, mouse, functional magnetic resonance imaging, blood oxygen level-dependent signal, multimodal imaging, wide-field imaging, fluorescent calcium imaging, functional connectivity, brain networks
MeSH: Brain*, Calcium*, Magnetic Resonance Imaging*, Optical Imaging*, Wakefulness*, Animals, Isoflurane, Male, Mice, Mice, Inbred C57BL, Oxygen (* major topic)
Topic: Functional Brain Connectivity Studies (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: NINDS NIH HHS (RF1 NS130069, R01 NS130069); NIMH NIH HHS (R25 MH119043)
Citations: not cited yet (Europe PMC); 68 references in the paper
Research resources: RRID:Addgene_100843

Abstract

Functional magnetic resonance imaging (fMRI) can be applied in mice and humans, making it a key technology in translational neuroimaging research. Yet, most fMRI studies in rodents use anesthesia to limit subject motion and stress. This puts a hard boundary on the range of brain and behavioral states that can be studied in animals, and deviates from the near-universal practice of imaging people while awake. Recent years have seen a push toward the development of acclimation protocols for performing fMRI in mice without anesthesia, but the results have been mixed. In parallel, imaging mice without anesthesia has become routine for complementary neuroimaging methods, including wide-field fluorescence calcium (WF-Ca2+) imaging. Our group works with a unique co-implementation of WF-Ca2+ and fMRI which enables the collection of complementary measures of brain function, but—until now—has necessitated the use of anesthesia. We present the first longitudinal protocol for simultaneous WF-Ca2+ and fMRI in awake mice. Our approach comprised a two-phase (biphasic) acclimation protocol that results in high-quality multimodal data. Comparisons of cortex-wide neuronal activity (WF-Ca2+ imaging) and blood-oxygen-level dependent fMRI signals between isoflurane-anesthetized and awake mice reveal both convergent and divergent patterns in brain function between modalities and across time.

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.

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Data

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Data and Code Availability

All data and codes used in this manuscript will be rendered available by the corresponding authors upon request.

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

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 7 authors, 9 keywords, 11 MeSH terms, 2 funders, 67 references, 1 RRID.

Cite

This paper

Mandino, F., Kang, T., Shen, X., Horien, C., Papademetris, X., Strittmatter, S. M., & Lake, E. M. (2026). Biphasic acclimation for simultaneous wide-field fluorescent Ca<sup>2+</sup> imaging and fMRI of awake mice. Imaging neuroscience (Cambridge, Mass.), 4, IMAG.a.1357. https://doi.org/10.1162/imag.a.1357

BibTeX

@article{mandino2026biphasic,
author = {Mandino, Francesca and Kang, Taekyung and Shen, Xilin and Horien, Corey and Papademetris, Xenophon and Strittmatter, Stephen M and Lake, Evelyn MR},
title = {{Biphasic acclimation for simultaneous wide-field fluorescent Ca\<sup\>2+\</sup\> imaging and fMRI of awake mice}},
journal = {Imaging neuroscience (Cambridge, Mass.)},
year = {2026},
month = sep,
volume = {4},
pages = {IMAG.a.1357},
publisher = {MIT Press},
issn = {2837-6056},
doi = {10.1162/imag.a.1357},
url = {https://doi.org/10.1162/imag.a.1357},
pmid = {42730032},
pmcid = {PMC13563530}
}

RIS

TY - JOUR
AU - Mandino, Francesca
AU - Kang, Taekyung
AU - Shen, Xilin
AU - Horien, Corey
AU - Papademetris, Xenophon
AU - Strittmatter, Stephen M
AU - Lake, Evelyn MR
TI - Biphasic acclimation for simultaneous wide-field fluorescent Ca<sup>2+</sup> imaging and fMRI of awake mice
T2 - Imaging neuroscience (Cambridge, Mass.)
J2 - Imaging Neurosci (Camb)
PY - 2026
DA - 2026/09/10
VL - 4
SP - IMAG.a.1357
SN - 2837-6056
PB - MIT Press
DO - 10.1162/imag.a.1357
UR - https://doi.org/10.1162/imag.a.1357
LA - en
ER -

CSL-JSON

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