Quantitative longitudinal T2* mapping for assessing placental function and association with adverse pregnancy outcomes across gestation

Abstract

Existing methods for evaluating in vivo placental function fail to reliably detect pregnancies at-risk for adverse outcomes prior to maternal and/or fetal morbidity. Here we report the results of a prospective dual-site longitudinal clinical study of quantitative placental T2* as measured by blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI). The objectives of this study were: 1) to quantify placental T2* at multiple time points across gestation, and its consistency across sites, and 2) to investigate the association between placental T2* and adverse outcomes. 797 successful imaging studies, at up to three time points between 11 and 38 weeks of gestation, were completed in 316 pregnancies. Outcomes were stratified into three groups: (UN) uncomplicated/normal pregnancy, (PA) primary adverse pregnancy, which included hypertensive disorders of pregnancy, birthweight <5th percentile, and/or stillbirth or fetal death, and (SA) secondary abnormal pregnancy, which included abnormal prenatal conditions not included in the PA group such as spontaneous preterm birth or fetal anomalies. Of the 316 pregnancies, 198 (62.6%) were UN, 70 (22.2%) PA, and 48 (15.2%) SA outcomes. We found that the evolution of placental T2* across gestation was well described by a sigmoid model, with T2* decreasing continuously from a high plateau level early in gestation, through an inflection point around 30 weeks, and finally approaching a second, lower plateau in late gestation. Model regression revealed significantly lower T2* in the PA group than in UN pregnancies starting at 15 weeks and continuing through 33 weeks. T2* percentiles were computed for individual scans relative to UN group regression, and z-scores and receiver operating characteristic (ROC) curves calculated for association of T2* with pregnancy outcome. Overall, differences between UN and PA groups were statistically significant across gestation, with large effect sizes in mid- and late- pregnancy. The area under the curve (AUC) for placental T2* percentile and PA pregnancy outcome was 0.71, with the strongest predictive power (AUC of 0.76) at the mid-gestation time period (20–30 weeks). Our data demonstrate that placental T2* measurements are strongly associated with pregnancy outcomes often attributed to placental insufficiency. Trial registration: ClinicalTrials.gov: NCT02749851.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease

“…As expected, we show that placental volume increases with advancing gestation. Consistent with previous work, we also identify a decrease in both T2* and ADC values with advancing gestations 39,40,62 , that appear consistent in healthy participants undergoing two scans 63 .…”

“…Placental MRI is a safe, non-invasive technique allowing such in-utero analysis, with both T2*-relaxation and diffusion imaging techniques used to assess placental function and microstructure throughout gestation [35][36][37][38][39] . T2*-relaxation exploits the blood oxygen level dependent effect linking shorter T2* values to, amongst other factors, a higher concentration of deoxygenated hemoglobin, and is often interpreted as a proxy for placental oxygenation or function 40,41 .…”

“…T2*-relaxation exploits the blood oxygen level dependent effect linking shorter T2* values to, amongst other factors, a higher concentration of deoxygenated hemoglobin, and is often interpreted as a proxy for placental oxygenation or function 40,41 . Since placental T2* is sensitive to the balance between oxygenated maternal blood delivery and fetal oxygen demand, it is particularly well-suited to identify altered placental oxygenation or blood ow patterns, as might be seen in CHD 20,39,[41][42][43][44][45] .…”

Assessing within‐subject rates of change of placental MRI diffusion metrics in normal pregnancy

“…Similarly, whereas work investigating quantitative longitudinal placental $$$ {\mathrm{T}}_2^{\ast } $$$ values in a large cohort of normal pregnancies has recently been published, 26 ours is the first study that reports similar longitudinal measurements for both placental $$$ {\mathrm{T}}_2^{\ast } $$$ and ADC rates of change within individual pregnancies. This provides a useful benchmark against which to compare how joint placental $$$ {\mathrm{T}}_2^{\ast } $$$ ADC trajectories may change over gestation in pregnancies affected by placental pathology.…”

Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI

“…The placental phenotype in control pregnancies is in line with previous work: the reduction in T2* across gestation in normal pregnancies has been demonstrated using both our imaging protocols 36 and those of others. 37,38 As previously demonstrated, there is overlap between chronic hypertensive pregnancies and normal pregnancies in terms of mean T2*, skewness, and kurtosis. 20 Pregnancies affected by preeclampsia are typically outliers in all domains.…”