BackgroundRecently, dynamic contrast‐enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions.PurposeTo measure cotyledon‐specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury.Study TypeProspective animal model.SubjectsPlacental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 μg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165).Field Strength/Sequence3 T, T1‐weighted spoiled gradient echo sequence (product sequence, DISCO).AssessmentSource images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP‐1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals.Statistical TestsWilcoxon rank sum test, significance level P < 0.05.ResultsNo motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute−1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel‐treated (single dose) animal and both Tisseelx3 (triple dose) animals.Data ConclusionThis study demonstrates the feasibility of cotyledon‐specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol‐enhanced DCE MRI.Level of EvidenceNATechnical EfficacyStage 2

中文翻译：

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使用 Ferumoxytol 动态对比增强 MRI 评估恒河猴胎盘损伤的子叶特异性血流

背景最近，以费鲁莫托作为造影剂的动态对比增强（DCE）MRI最近被引入用于胎盘结构和功能的无创评估。然而，尚未在病理条件下得到证实。目的在局部胎盘损伤的新型动物模型中使用费鲁莫托 DCE MRI 测量子叶特异性恒河猴母体胎盘血流量。研究类型前瞻性动物模型。受试者胎盘注射 Tisseel（3 次，每次 0.5 mL）在大约妊娠日（GD 101）的总共 11 只恒河猴妊娠中，进行了 1 次（1.5 mL 和 2 次）、单核细胞趋化蛋白 1（3 次 100 μg）和 3 次生理盐水作为对照。DCE MRI 扫描在注射前 (GD 100) 和注射后 (GD 115 和 GD 145)（术语 = GD 165）进行。场强/序列 3 T、T1 加权破坏梯度回波序列（产品序列，DISCO）。评估源图像检查母亲或胎儿的运动伪影。对动态图像系列进行胎盘分割和 DCE 处理，以测量子叶比体积、流量和归一化流量。对对照、Tisseel 和 MCP-1 动物进行总体胎盘组织病理学检查，并记录组织梗塞和坏死区域。对两只 Tisseelx3 动物进行了潜在坏死组织的目视检查。统计测试Wilcoxon 秩和检验，显着性水平磷< 0.05。结果未观察到运动伪影。对于用 1.5 mL Tisseel 处理的组，在成像的第三个妊娠时间点（第 ~145 天）观察到子叶体积、流量和每个子叶的归一化流量显着降低，平均归一化流量为 0.53 分钟−1。初步组织病理学分析显示一只 Tisseel 治疗（单剂量）动物和两只 Tisseelx3（三剂量）动物中选定子叶的组织坏死区域。数据结论本研究证明了在多个妊娠时间点和损伤下进行子叶特异性功能分析的可行性通过 Ferumoxytol 增强 DCE MRI 在胎盘恒河猴模型中进行检测。证据级别NA 技术功效第 2 阶段