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

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.

Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics

“…The updated ARRIVE guideline 2.0 provides a general checklist of in vivo experiments to facilitate the reproducibility of the results and methodological rigor ( 177 , 178 ). Previous systematic reviews have systematically evaluated the choice of anesthetic/sedative regimen and the variation in fMRI rodent imaging ( 179 – 181 ). In a recent multicenter study in the United States and Europe, standardization of the preclinical PET/CT acquisition and reconstruction protocols have been shown to increase the quantitative accuracy as well as the reproducibility of imaging results ( 182 ).…”

Magnetic Resonance Imaging in Tauopathy Animal Models

“…In addition to the isoflurane or low-dose isoflurane + medetomidine sedation that has been used in the aforementioned studies, ketamine and xylazine mixtures have also been reportedly used to achieve stable states in mice or rats ( Grandjean et al, 2014b , 2020 ; Shim et al, 2018 ; Mandino et al, 2020 ). A recent systematic review summarized the influence of anesthetics, doses, and timing on fMRI results in rodents ( Steiner et al, 2021 ). Thus, standardization of pipelines is important for better interpretation of the results from fMRI studies.…”

Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks

“…In this study, our stability of fMRI measurements for BOLD signal time courses and localization of the activation could be found as long as the above experimental methods including the anesthetic protocol with optimal dose ranges and imaging time points, parameter manipulation for somatosensory stimulation, and fMRI preprocessing and analysis were followed 60 , which therefore resulting in the reproducibility and spatial agreement of BOLD responses to contralateral forepaw stimulation on S1FL and M1 cortical regions over different mice.…”