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Review
. 2021 Jan 15;11(1):199.
doi: 10.3390/ani11010199.

Systematic Review: Anesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)-Part B: Effects of Anesthetic Agents, Doses and Timing

Aline R Steiner  1 , Frédérik Rousseau-Blass  2 , Aileen Schroeter  3 , Sonja Hartnack  4 , Regula Bettschart-Wolfensberger  1
Affiliations
Review

Systematic Review: Anesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)-Part B: Effects of Anesthetic Agents, Doses and Timing

Aline R Steiner et al. Animals (Basel). .

Abstract

In rodent models the use of functional magnetic resonance imaging (fMRI) under anesthesia is common. The anesthetic protocol might influence fMRI readouts either directly or via changes in physiological parameters. As long as those factors cannot be objectively quantified, the scientific validity of fMRI in rodents is impaired. In the present systematic review, literature analyzing in rats and mice the influence of anesthesia regimes and concurrent physiological functions on blood oxygen level dependent (BOLD) fMRI results was investigated. Studies from four databases that were searched were selected following pre-defined criteria. Two separate articles publish the results; the herewith presented article includes the analyses of 83 studies. Most studies found differences in BOLD fMRI readouts with different anesthesia drugs and dose rates, time points of imaging or when awake status was compared to anesthetized animals. To obtain scientifically valid, reproducible results from rodent fMRI studies, stable levels of anesthesia with agents suitable for the model under investigation as well as known and objectively quantifiable effects on readouts are, thus, mandatory. Further studies should establish dose ranges for standardized anesthetic protocols and determine time windows for imaging during which influence of anesthesia on readout is objectively quantifiable.

Keywords: BOLD fMRI; anesthesia regime; anesthetic protocol; isoflurane; medetomidine; mouse; rat; validity; α-chloralose.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Effects of anesthetic doses on baseline blood oxygen level dependent (BOLD) signal, responses to peripheral and central stimulation and functional connectivity in rats and mice. Yes = differences between doses were clearly observed; partial = differences between doses were observed for some outcomes, analyses or animals, but not consistently, or quantitative differences were reported, but statistical significance unclear; and no = no differences between doses were observed. When datasets were re-analyzed, findings were pooled and one data point per specific comparison (i.e., per anesthetic per type of functional magnetic resonance imaging (fMRI)) displayed. (dex)medetomidine = medetomidine or dexmedetomidine was studied. (S-)ketamine = ketamine or S-ketamine was studied. Not all references are discussed in the text [43,44], but a summary of the main findings as well as the doses of anesthetics are provided for references with the symbols ■ or □ in Supplementary Materials Tables S2 and S5, with symbols ● or ○ in Supplementary Materials Tables S3 and S5, and for references with symbol ★ in Supplementary Materials Tables S4 and S6.
Figure 2
Figure 2
Effects of time points of imaging on baseline BOLD signal, responses to peripheral and central stimulation and functional connectivity in rats and mice. Yes = differences between timepoints were clearly observed; partial = differences between timepoints were observed for some outcomes, analyses or animals, but not consistently, or quantitative differences were reported, but statistical significance unclear; and no = no differences between timepoints were observed. When datasets were re-analyzed, findings were pooled and one data point per specific comparison (i.e., per anesthetic per type of fMRI) displayed. (dex)medetomidine = medetomidine or dexmedetomidine was studied. Not all references are discussed in the text [43,45], but a summary of the main findings as well as the doses of anesthetics are provided for references with the symbols ■ or □ in Supplementary Materials Tables S2 and S5, with symbols ● or ○ in Supplementary Materials Table S3 and S5, and for references with symbol ★ in Supplementary Materials Tables S4 and S6.
Figure 3
Figure 3
Distribution of pairwise comparisons of anesthetics for (a) stimulation fMRI and (b) rsfMRI. The size of the symbol represents the total number of datasets; the number of references may be higher.
Figure 4
Figure 4
Comparison of anesthetized versus awake imaging for baseline BOLD signal, responses to peripheral and central stimulation and functional connectivity in rats and mice. Yes = differences between anesthetized and awake imaging were clearly observed; partial = differences between anesthetized and awake imaging were observed for some outcomes, analyses or animals, but not consistently, or quantitative differences were reported, but statistical significance unclear; and no = no differences between anesthetized and awake imaging were observed. When datasets were re-analyzed, findings were pooled and one data point per specific comparison (i.e., per anesthetic per type of fMRI) displayed. (dex)medetomidine = medetomidine or dexmedetomidine was studied. A summary of the main findings as well as the doses of anesthetics are provided for references with the symbols ■ or □ in Supplementary Materials Tables S2 and S5, with symbols ● or ○ in Supplementary Materials Tables S3 and S5, and for references with symbol ★ in Supplementary Materials Tables S4 and S6.
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References

    1. Martin C. Contributions and complexities from the use of in-vivo animal models to improve understanding of human neuroimaging signals. Front. Neurosci. 2014;8:211. doi: 10.3389/fnins.2014.00211. - DOI - PMC - PubMed
    1. Jonckers E., Shah D., Hamaide J., Verhoye M., Van der Linden A. The power of using functional fmri on small rodents to study brain pharmacology and disease. Front Pharmacol. 2015;6:231. doi: 10.3389/fphar.2015.00231. - DOI - PMC - PubMed
    1. Pan W.J., Billings J.C.W., Grooms J.K., Shakil S., Keilholz S.D. Considerations for resting state functional mri and functional connectivity studies in rodents. Front. Neurosci. 2015;9:269. doi: 10.3389/fnins.2015.00269. - DOI - PMC - PubMed
    1. Huo B.X., Smith J.B., Drew P.J. Neurovascular coupling and decoupling in the cortex during voluntary locomotion. J. Neurosci. 2014;34:10975–10981. doi: 10.1523/JNEUROSCI.1369-14.2014. - DOI - PMC - PubMed
    1. Shih Y.-Y.I., Chen C.-C.V., Shyu B.-C., Lin Z.-J., Chiang Y.-C., Jaw F.-S., Chen Y.-Y., Chang C. A new scenario for negative functional magnetic resonance imaging signals: Endogenous neurotransmission. J. Neurosci. 2009;29:3036–3044. doi: 10.1523/JNEUROSCI.3447-08.2009. - DOI - PMC - PubMed

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