A Description of the Imaging Innovations for Placental Assessment in Response to Environmental Pollution Study.

OBJECTIVE: The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN: Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS: In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION: Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

Characterization of Uterine Motion in Early Gestation Using MRI-Based Motion Tracking.

Magnetic resonance imaging (MRI) is a promising non-invasive imaging technique that can be safely used to study placental development and function. However, studies of the human placenta performed by MRI are limited by uterine motion and motion in the uterus during MRI remains one of the major limiting factors. Here, we aimed to investigate the characterization of uterine activity during MRI in the second trimester of pregnancy using MRI-based motion tracking. In total, 46 pregnant women were scanned twice (first scan between 14 and 18 weeks and second scan between 19 and 24 weeks), and 20 pregnant subjects underwent a single MRI between 14 and 18 weeks GA, resulting in 112 MRI scans. An MRI-based algorithm was used to track uterine motion in the superior-inferior and left-right directions. Uterine contraction and maternal motion cases were separated by the experts, and unpaired Wilcoxon tests were performed within the groups of gestational age (GA), fetal sex, and placental location in terms of the overall intensity measures of the uterine activity. In total, 22.3% of cases had uterine contraction during MRI, which increased from 18.6% at 14-18 weeks to 26.4% at 19-24 weeks GA. The dominant direction of the uterine contraction and maternal motion was the superior to the inferior direction during early gestation.

Human Placenta Blood Flow During Early Gestation With Pseudocontinuous Arterial Spin Labeling MRI.

BACKGROUND: Noninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known. PURPOSE: To derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion-related parameters and IPD. STUDY TYPE: Prospective. POPULATION: Eighty-four women completed two pCASL MRI scans (first; 14-18 weeks and second; 19-24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD. FIELD STRENGTH/SEQUENCE: 3T/T2 -weighted half-Fourier single-shot turbo spin-echo (HASTE) and pCASL. ASSESSMENT: Four perfusion-related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation. STATISTICAL TESTS: Comparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests. RESULTS: The difference between the first and second MRI scans was statistically significant for volume (156.6 cm3 vs. 269.7 cm3 , P < 0.001) and PBF (104.9 ml/100g/min vs. 111.3 ml/100g/min, P = 0.02) for normal subjects, indicating an increase in pregnancy with advancing gestation. Of the parameters tested, the difference between the normal and IPD subjects was most pronounced in hPBF (278.1 ml/100g/min vs. 180.7 ml/100g/min, P < 0.001) and relative hPBF (259.1% vs. 183.2%, P < 0.001) at 16 weeks. DATA CONCLUSION: The high perfusion-related image parameters for IPD were significantly decreased from normal pregnancy at 14-18 weeks of gestation. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;51:1247-1257.

3D R2* mapping of the placenta during early gestation using free-breathing multiecho stack-of-radial MRI at 3T.

BACKGROUND: Multiecho gradient-echo Cartesian MRI characterizes placental oxygenation by quantifying R2* . Previous research was performed at 1.5T using breath-held 2D imaging during later gestational age (GA). PURPOSE: To evaluate the accuracy and repeatability of a free-breathing (FB) 3D multiecho gradient-echo stack-of-radial technique (radial) for placental R2* mapping at 3T and report placental R2* during early GA. STUDY TYPE: Prospective. POPULATION: Thirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks GA. FIELD STRENGTH: 3T. SEQUENCE: FB radial. ASSESSMENT: Linear correlation (concordance coefficient, ρc ) and Bland-Altman analyses (mean difference, MD) were performed to evaluate radial R2* mapping accuracy compared to Cartesian in a phantom. Radial R2* mapping repeatability was characterized using the coefficient of repeatability (CR) between back-to-back scans. The mean and spatial coefficient of variation (CV) of R2* was determined for all subjects, and separately for anterior and posterior placentas, at each GA range. STATISTICAL TESTS: ρc was tested for significance. Differences in mean R2* and CV were tested using Wilcoxon Signed-Rank and Rank-Sum tests. P < 0.05 was considered significant. Z-scores for the IPD subjects were determined. RESULTS: FB radial demonstrated accurate (ρc ≥0.996; P < 0.001; |MD|<0.2s-1 ) and repeatable (CR<4s-1 ) R2* mapping in a phantom, and repeatable (CR≤4.6s-1 ) R2* mapping in normal subjects. At 3T, placental R2* mean ± standard deviation was 12.9s-1 ± 2.7s-1 for 14-18 and 13.2s-1 ± 1.9s-1 for 19-23 weeks GA. The CV was significantly greater (P = 0.043) at 14-18 (0.63 ± 0.12) than 19-23 (0.58 ± 0.13) weeks GA. At 19-23 weeks, the CV was significantly lower (P < 0.001) for anterior (0.49 ± 0.08) than posterior (0.67 ± 0.11) placentas. One IPD subject had a lower mean R2* than normal subjects at both GA ranges (Z<-2). DATA CONCLUSION: FB radial provides accurate and repeatable 3D R2* mapping for the entire placenta at 3T during early GA. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:291-303.

A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy.

PURPOSE: Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort. METHODS: We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression. RESULTS: We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR = 2.57, P = 0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HR = 0.16, P < 0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent. CONCLUSION: Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.

Measuring human placental blood flow with multidelay 3D GRASE pseudocontinuous arterial spin labeling at 3T.

BACKGROUND: Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured noninvasively using arterial spin labeling (ASL). PURPOSE: To present a multidelay pseudocontinuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume gradient- and spin-echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility. STUDY TYPE: This was a prospective study. SUBJECTS: Thirty-four pregnant women. FIELD STRENGTH/SEQUENCE: Multidelay 3D inner-volume GRASE pCASL sequence on 3T MR scanners. ASSESSMENT: Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14-16 and 19-22 weeks of gestational age, respectively. Placental perfusion was measured using the free-breathing pCASL sequence at three postlabeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT. STATISTICAL TESTS: A paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. A two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch. RESULTS: The mean PBF and ATT for the second trimester were 111.4 ± 26.7 ml/100g/min and 1387.5 ± 88.0 msec, respectively. The average PBF increased by 10.4% (P < 0.05), while no significant change in ATT (P = 0.72) was found along gestational ages during the second trimester. PBF decreased 20.3% (P < 0.01) in subjects with early diastolic notches in ultrasound flow waveform patterns. DATA CONCLUSION: Multidelay pCASL with inner-volume 3D GRASE is promising for noninvasive assessment of PBF during pregnancy. Its clinical use for the detection of aberrations in placental function and prediction of fetal developmental disorders awaits evaluation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1667-1676.