OS044. Morphological differences in murine placenta detected by magneticresonance imaging measurements of T2 relaxation times in mouse models ofpreeclampsia

Abstract

We have demonstrated that morphologically distinct regions of the murine placenta can be detected by magnetic resonance imaging (MRI), with image contrast arising from the variation in T2 relaxation times between regions and dependent upon blood flow. Previous studies of human placenta by other groups have shown a homogeneous tissue with correlation of relaxation times with gestational age and a trend for shorter relaxation times in pregnancies complicated by preeclampsia and fetal growth restriction. The ability to detect morphological changes and alterations in blood flow in experimental models of preeclampsia would be a significant boost in understanding the relationship between abnormal placental implantation, reduced placental perfusion, inflammatory cytokines, angiogenic molecules and other factors that may play a role in the syndrome. The aim of this study was to investigate whether morphological changes or abnormalities can be detected by T2 mapping in the placenta of mice subject to two experimental models of preeclampsia (reduced uterine perfusion pressure (RUPP) model and TNF-α induced model). Pregnant C57BL/6JArc mice were, on day 13.5 of gestation, either subject to a unilateral ligation of the right uterine artery (RUPP) (n=2) or given an infusion of TNF-α by subcutaneous insertion of a mini-osmotic pump primed to deliver 500ng/kg/day for 4days (n=2). Controls were normal pregnant (n=2), sham-operated (n=1) or saline infused animals(n=1). MRI images were acquired on anaesthetised mice on day 17.5 of gestation using a Bruker Avance 11.7 Tesla wide-bore spectrometer with micro-imaging probe capable of generating gradients of 0.45T/m. T2 measurements were acquired using an MSME sequence protocol (Bruker MSME-T2-map) with an in-plane resolution of 0.1-0.2mm. Matlab was used to generate R2 (i.e.,1/T2) maps from the acquired data with the T2 values being calculated from selected regions of interest from 2-6 individual placenta from each mouse. Differences in the pattern of the regions of T2 contrast in the placenta were observed between normal, TNF-α treated and RUPP mice. The ratio of T2 values from the inner two regions was also significantly altered in TNF-α treated 1.98±0.09 (p=0.007); RUPP 1.94±0.11 (p=0.006) compared to normal animals 2.5±0.1 . These results demonstrate that morphological differences or abnormalities can be detected by T2 mapping in the placenta of mice subject to experimental models of preeclampsia and may be used to analyse changes quantitatively. This technology has the potential to be used when studying the dynamic changes in the placenta of pregnancies complicated by preeclampsia.