Vitamin H (biotin) is delivered to the fetus transplacentally by an active biotin-transport mechanism and is critical for fetal development. Our objective was to develop a comprehensive MRI technique for mapping biotin transporter activity in the murine placenta. Visualization of transporter activity can employ MRI’s unique T₂*-dependent signal ‘off-switch’, which is triggered by transporter mediated aggregation of biotinylated contrast agent (b-BSA-Gd-DTPA). MRI data were collected from pregnant mice after administration of b-BSA-Gd-DTPA and analyzed using a new sub-voxel biophysical signal model. Validation experiments included competition with native biotin, comparative tests using PET, histology, and ICPMS. MRI signal was governed by binding, aggregation, and clearance of biotin (confirmed by histology). Signal dynamics reflected the placenta’s perfusion pattern modulated by biotin transporter activity and trophoblast mediated retention, and were in congruence with a three-compartment sub-voxel model. Pre-saturation of the transporters with free biotin suppressed b-BSA-Gd-DTPA uptake. The results were confirmed by PET, histology and ICPMS. The presented MRI-based platform allows to track activity of essential molecular transporters in the placenta, reflecting a transporter-mediated uptake, followed by retention and aggregation, and recycling associated with the large b-BSA-Gd-DTPA conjugate. The presented DCE-MRI technique can furthermore be used to map and characterize microstructural compartmentation and transporter activity without exposing the fetus to contrast media.

维生素 H（生物素）通过活性生物素转运机制经胎盘输送给胎儿，对胎儿发育至关重要。我们的目标是开发一种全面的 MRI 技术，用于绘制小鼠胎盘中生物素转运蛋白的活性。转运蛋白活动的可视化可以使用 MRI 独特的 T ₂* 依赖性信号“关闭开关”，由转运蛋白介导的生物素化造影剂 (b-BSA-Gd-DTPA) 聚集触发。在施用 b-BSA-Gd-DTPA 后从怀孕小鼠收集 MRI 数据，并使用新的亚体素生物物理信号模型进行分析。验证实验包括与天然生物素的竞争、使用 PET、组织学和 ICPMS 的比较测试。MRI 信号受生物素的结合、聚集和清除（经组织学证实）控制。信号动力学反映了由生物素转运蛋白活性和滋养层介导的保留调节的胎盘灌注模式，并且与三室亚体素模型一致。具有游离生物素的转运蛋白的预饱和抑制了 b-BSA-Gd-DTPA 的摄取。结果由PET、组织学和ICPMS证实。所提出的基于 MRI 的平台允许跟踪胎盘中基本分子转运蛋白的活动，反映转运蛋白介导的摄取，然后是保留和聚集，以及与大 b-BSA-Gd-DTPA 共轭物相关的回收。此外，所提出的 DCE-MRI 技术还可用于绘制和表征微结构区室和转运蛋白活动，而无需将胎儿暴露于造影剂。