Department of Experimental Neurology and Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Sci Rep. 2021 Jan 22;11(1):2126. doi: 10.1038/s41598-020-80408-9.
Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. The goal of this exploratory study was to establish a technique to noninvasively characterize placental partial pressure of oxygen (PO) in vivo in the Lgals1 (lectin, galactoside-binding, soluble, 1) deficient mouse model of preeclampsia using fluorine magnetic resonance imaging. We hypothesized a decrease in placental oxygenation in knockout mice. Wildtype and knockout animals received fluorescently labeled perfluoro-5-crown-15-ether nanoemulsion i.v. on day E14-15 during pregnancy. Placental PO was assessed via calibrated F MRI saturation recovery T mapping. A gas challenge with varying levels of oxygen in breathing air (30%, 60% and 100% O) was used to validate that changes in oxygenation can be detected in freely breathing, anesthetized animals. At the end of the experiment, fluorophore-coupled lectin was injected i.v. to label the vasculature for histology. Differences in PO between breathing conditions and genotype were statistically analyzed with linear mixed-effects modeling. As expected, a significant increase in PO with increasing oxygen in breathing air was found. PO in Lgals1 knockout animals was decreased but this effect was only present at 30% oxygen in breathing air, not at 60% and 100%. Histological examinations showed crossing of the perfluorocarbon nanoemulsion to the fetal blood pool but the dominating contribution of F MR signal is estimated at > 70% from maternal plasma based on volume fraction measurements of previous studies. These results show for the first time that F MRI can characterize oxygenation in mouse models of placental malfunction.
胎盘灌注不足和缺氧是胎儿发育过程中出现并发症的关键因素，如胎儿生长受限和子痫前期。为了在小鼠模型中研究疾病机制，开发胎盘缺氧的定量生物标志物是先决条件。这项探索性研究的目的是建立一种使用氟磁共振成像（F MRI）非侵入性地描述子痫前期 Lgals1（lectin，galactoside-binding，soluble，1）缺失小鼠模型胎盘局部氧分压（PO ）的技术。我们假设敲除小鼠的胎盘氧合作用降低。野生型和敲除型动物在妊娠第 E14-15 天接受静脉注射荧光标记的全氟-5-冠-15-醚纳米乳液。通过校准 F MRI 饱和恢复 T 映射评估胎盘 PO。使用呼吸空气中不同氧含量的气体挑战（30%、60%和 100% O）来验证在自由呼吸、麻醉动物中可以检测到氧合变化。实验结束时，静脉注射荧光偶联凝集素标记血管用于组织学检查。使用线性混合效应模型对呼吸条件和基因型之间的 PO 差异进行统计学分析。正如预期的那样，在呼吸空气中增加氧气时，PO 显著增加。Lgals1 敲除动物的 PO 降低，但这种效应仅在呼吸空气中 30%的氧气时存在，而在 60%和 100%的氧气时不存在。组织学检查显示全氟碳纳米乳液穿过胎盘转移到胎儿血池，但基于先前研究的体积分数测量，F MR 信号的主要贡献估计超过 70%来自母体血浆。这些结果首次表明，F MRI 可以描述胎盘功能障碍小鼠模型的氧合作用。
