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.

Abstract

Simple SummaryTo understand brain function in rats and mice functional magnetic resonance imaging of the brain is used. With this type of “brain scan” regional changes in blood flow and oxygen consumption are measured as an indirect surrogate for activity of brain regions. Animals are often anesthetized for the experiments to prevent stress and blurred images due to movement. However, anesthesia may alter the measurements, as blood flow within the brain is differently affected by different anesthetics, and anesthetics also directly affect brain function. Consequently, results obtained under one anesthetic protocol may not be comparable with those obtained under another, and/or not representative for awake animals and humans. We have systematically searched the existing literature for studies analyzing the effects of different anesthesia methods or studies that compared anesthetized and awake animals. Most studies reported that anesthetic agents, doses and timing had an effect on functional magnetic resonance imaging results. To obtain results which promote our understanding of brain function, it is therefore essential that a standard for anesthetic protocols for functional magnetic resonance is defined and their impact is well characterized.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.