Magnetic resonance imaging of hypoxic injury to the murine placenta

Departments of 1 Obstetrics and Gynecology, 2 Radiology, and 3 Chemistry, Washington University, St. Louis, Missouri, and 4 Magee Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania Submitted July 17, 2009 ; accepted in final form November 12, 2009 We assessed the use of magnetic resonance imaging (MRI) to define placental hypoxic injury associated with fetal growth restriction. On embryonic day 18.5 (E18.5) we utilized dynamic contrast-enhanced (DCE)-MRI on a 4.7-tesla small animal scanner to examine the uptake and distribution of gadolinium-based contrast agent. Quantitative DCE parameter analysis was performed for the placenta and fetal kidneys of three groups of pregnant C57BL/6 mice: 1 ) mice that were exposed to F I O 2 = 12% between E15.5 and E18.5, 2 ) mice in normoxia with food restriction similar to the intake of hypoxic mice between E15.5 and E18.5, and 3 ) mice in normoxia that were fed ad libitum. After imaging, we assessed fetoplacental weight, placental histology, and gene expression. We found that dams exposed to hypoxia exhibited fetal growth restriction (weight reduction by 28% and 14%, respectively, P < 0.05) with an increased placental-to-fetal ratio. By using MRI-based assessment of placental contrast agent kinetics, referenced to maternal paraspinous muscle, we found decreased placental clearance of contrast media in hypoxic mice, compared with either control group (61%, P < 0.05). This was accompanied by diminished contrast accumulation in the hypoxic fetal kidneys (23%, P < 0.05), reflecting reduced transplacental gadolinium transport. These changes were associated with increased expression of placental Phlda2 and Gcm1 transcripts. Exposure to hypoxia near the end of mouse pregnancy reduces placental perfusion and clearance of contrast. MRI-based DCE imaging provides a novel tool for dynamic, in vivo assessment of placental function. placenta; DCE-MRI; fetal growth restriction; hypoxia Address for reprint requests and other correspondence: Y. Sadovsky, Magee-Womens Research Institute, 204 Craft Ave. Rm. A608, Pittsburgh, PA 15213 (e-mail: ysadovsky{at}mwri.magee.edu ).