Systematic Review: Anaesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)-Part A: Effects of Changes in Physiological Parameters.

Aline R Steiner,Sonja Hartnack,Regula Bettschart-Wolfensberger,Frédérik Rousseau-Blass,Aileen Schroeter

doi:10.3389/fnins.2020.577119

Abstract

Background: To understand brain function in health and disease, functional magnetic resonance imaging (fMRI) is widely used in rodent models. Because animals need to be immobilised for image acquisition, fMRI is commonly performed under anaesthesia. The choice of anaesthetic protocols and may affect fMRI readouts, either directly or via changing physiological balance, and thereby threaten the scientific validity of fMRI in rodents.Methods: The present study systematically reviewed the literature investigating the influence of different anaesthesia regimes and changes in physiological parameters as confounders of blood oxygen level dependent (BOLD) fMRI in rats and mice. Four databases were searched, studies selected according to pre-defined criteria, and risk of bias assessed for each study. Results are reported in two separate articles; this part of the review focuses on effects of changes in physiological parameters.Results: A total of 121 publications was included, of which 49 addressed effects of changes in physiological parameters. Risk of bias was high in all included studies. Blood oxygenation [arterial partial pressure of oxygen (paO2)], ventilation [arterial partial pressure of carbon dioxide (paCO2)] and arterial blood pressure affected BOLD fMRI readouts across various experimental paradigms.Conclusions: Blood oxygenation, ventilation and arterial blood pressure should be monitored and maintained at stable physiological levels throughout experiments. Appropriate anaesthetic management and monitoring are crucial to obtain scientifically valid, reproducible results from fMRI studies in rodent models.

Highlights

Rats and mice commonly undergo functional magnetic resonance imaging when models of human brain function are studied (Martin, 2014; Jonckers et al, 2015; Pan et al, 2015).As all animal experiments, rodent fMRI studies are subject to harm-benefit analysis
Mechanical ventilation is generally recommended to keep paCO2 constant and should be used together with monitoring of end-tidal CO2
As the majority of included studies did report effects of paO2 (mmHg) paCO2 (mmHg)

Summary

Introduction

Rats and mice commonly undergo functional magnetic resonance imaging (fMRI) when models of human brain function (physiological as well as pathological) are studied (Martin, 2014; Jonckers et al, 2015; Pan et al, 2015). Rodent fMRI studies are subject to harm-benefit analysis. Construct validity is defined as “The degree to which inferences are warranted from the sampling properties of an experiment (e.g., units, settings, treatments and outcomes) to the entities these samples are intended to represent” (Würbel et al, 2014). Internal validity refers to “The extent to which the design, conduct, and analysis of the experiment eliminate the possibility of bias so that the inference of a causal relationship between an experimental treatment and variation in an outcome measure is warranted,” and external validity is defined as the extent to which findings can be generalised (Würbel et al, 2014). The choice of anaesthetic protocols and may affect fMRI readouts, either directly or via changing physiological balance, and thereby threaten the scientific validity of fMRI in rodents

Methods

Results

Conclusion