title: Optimization of anesthesia protocol for resting-state fMRI in mice based on differential effects of anesthetics on functional connectivity patterns.
abstract: Resting state-fMRI (rs-fMRI) in mice allows studying mechanisms underlying functional connectivity (FC) as well as alterations of FC occurring in murine models of neurological diseases. Mouse fMRI experiments are typically carried out under anesthesia to minimize animal movement and potential distress during examination. Yet, anesthesia inevitably affects FC patterns. Such effects have to be understood for proper interpretation of data. We have compared the influence of four commonly used anesthetics on rs-fMRI. Rs-fMRI data acquired under isoflurane, propofol, and urethane presented similar patterns when accounting for anesthesia depth. FC maps displayed bilateral correlation with respect to cortical seeds, but no significant inter-hemispheric striatal connectivity. In contrast, for medetomidine, we detected bilateral striatal but compromised inter-hemispheric cortical connectivity. The spatiotemporal patterns of the rs-fMRI signal have been rationalized considering anesthesia depth and pharmacodynamic properties of the anesthetics. Our results bridge the results from different studies from the burgeoning field of mouse rs-fMRI and offer a framework for understanding the influences of anesthetics on FC patterns. Utilizing this information, we suggest the combined use of medetomidine and isoflurane representing the two proposed classes of anesthetics; the combination of low doses of the two anesthetics retained strong correlations both within cortical and subcortical structures, without the potential seizure-inducing effects of medetomidine, rendering this regimen an attractive anesthesia for rs-fMRI in mice.
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Winterthurer-Str. 190, 8057 Zurich, Switzerland.
authors.forename: Joanes
authors.initials: J
authors.lastname: Grandjean
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Winterthurer-Str. 190, 8057 Zurich, Switzerland.
authors.forename: Aileen
authors.initials: A
authors.lastname: Schroeter
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zurich, Switzerland.
authors.forename: Imene
authors.initials: I
authors.lastname: Batata
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Winterthurer-Str. 190, 8057 Zurich, Switzerland; Institute of Pharmacology and Toxicology, University of Zurich, Winterthurer-Str. 190, 8057 Zurich, Switzerland. Electronic address: rudin@biomed.ee.ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
mesh_terms: D000758:Anesthesia / Q000592:standards; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002985:Clinical Protocols; D005260:Female; D007530:Isoflurane / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D020926:Medetomidine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology; D012146:Rest / Q000502:physiology; D014520:Urethane / Q000494:pharmacology
chemical_list: D000777:Anesthetics; D014520:Urethane; D007530:Isoflurane; D020926:Medetomidine; D015742:Propofol
keywords: Anesthesia; Functional connectivity; Mouse; Resting state-fMRI