Functional Imaging Laboratory, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.
Georg-August University of Göttingen, Göttingen, Germany.
Sci Rep. 2019 Nov 13;9(1):16673. doi: 10.1038/s41598-019-53144-y.
Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). Despite this, it has not yet been thoroughly established how commonly reported fMRI readouts evolve over several hours of medetomidine anesthesia and how they are affected by the precise timing, dose, and route of administration. We used four different protocols of medetomidine administration to anesthetize rats for up to six hours and repeatedly evaluated somatosensory stimulus-evoked BOLD responses and resting state functional connectivity. We found that the temporal evolution of fMRI readouts strongly depended on the method of administration. Intravenous administration of a medetomidine bolus (0.05 mg/kg), combined with a subsequent continuous infusion (0.1 mg/kg/h), led to temporally stable measures of stimulus-evoked activity and functional connectivity throughout the anesthesia. Deviating from the above protocol-by omitting the bolus, lowering the medetomidine dose, or using the subcutaneous route-compromised the stability of these measures in the initial two-hour period. We conclude that both an appropriate protocol of medetomidine administration and a suitable timing of fMRI experiments are crucial for obtaining consistent results. These factors should be considered for the design and interpretation of future rat fMRI studies.
美托咪定已成为长时间血氧水平依赖（BOLD）功能磁共振成像（fMRI）麻醉大鼠的首选药物。尽管如此，仍未彻底确定在美托咪定麻醉数小时内，常见报道的 fMRI 读出值如何演变，以及它们如何受到精确的给药时间、剂量和途径的影响。我们使用四种不同的美托咪定给药方案麻醉大鼠长达 6 小时，并反复评估躯体感觉刺激诱发的 BOLD 反应和静息状态功能连接。我们发现，fMRI 读出值的时间演变强烈依赖于给药方法。静脉注射美托咪定推注（0.05mg/kg），并随后持续输注（0.1mg/kg/h），可在整个麻醉过程中产生稳定的刺激诱发活动和功能连接的测量值。与上述方案不同——省略推注、降低美托咪定剂量或使用皮下途径——会在最初的两小时内破坏这些测量值的稳定性。我们得出结论，美托咪定给药的适当方案和 fMRI 实验的合适时间对于获得一致的结果至关重要。这些因素应在未来的大鼠 fMRI 研究的设计和解释中加以考虑。
