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

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 (p a O 2)], ventilation [arterial partial pressure of carbon dioxide (p a CO 2)] 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.

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

“…Results of the systematic search, including a PRISMA flow chart as well as detailed results of the risk of bias assessment of all included studies, are reported in part a of the review [ 15 ].…”

“…An overview which anesthetics have been compared for stimulation and rsfMRI in rats and mice is given in Figure 3 , and in more detail in Supplementary Materials Table S1 , where for each reference it is listed which anesthetics were investigated. Studies which exclusively compared dose-dependence or time-dependence for two anesthetics are covered in previous sections, and results of studies which investigated effects of physiological parameter changes are covered in part a of this review [ 15 ]. Differences between anesthetics were found in all except three datasets (baseline BOLD signal after blood withdrawal, isoflurane versus halothane versus propofol [ 57 ]; response to peripheral electrical stimulation, medetomidine versus α-chloralose [ 50 ]; rsfMRI, isoflurane versus ketamine/xylazine [ 58 ]).…”

“…For a detailed description of the materials and methods used see part a of this review [ 15 ]. Preparation, performance and reporting of this systematic review followed the SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation, Radboud University, Nijmegen, The Netherlands) protocol for systematic reviews of animal intervention studies [ 16 ].…”

“…Finally, anesthetics induce agent-specific changes in systemic physiology, notably cardiovascular and respiratory parameters, which in turn may affect cerebral hemodynamics [ 15 ].…”

“…Part a [ 15 ] of this review showed that changes in physiological parameters confound results of BOLD fMRI studies when undetected—in particular arterial partial pressure of carbon dioxide (CO 2 ), blood oxygenation and arterial blood pressures. Establishment of standards for anesthetic management and monitoring was claimed.…”