Imaging Innovations for Placental Assessment in Response to Environmental Pollution (PARENTs)
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/13/2018 |
| Start Date: | October 2, 2015 |
| End Date: | September 2020 |
| Contact: | Sherin Devaskar, MD |
| Email: | SDevaskar@mednet.ucla.edu |
| Phone: | 310-825-5095 |
Imaging Innovations for Placental Assessment in Response to Environmental Pollution
How environmental pollution contributes to poor pregnancy outcome is poorly understood. The
first trimester of pregnancy is a particularly vulnerable time period for the developing
fetus and a mother's exposure to air pollution may alter the way that the placenta is
established and how it functions throughout the rest of pregnancy. This project aims to
expand and develop new MRI technologies to assess real-time placental structure and function
as pregnancy develops from the first to the third trimester so that early detection,
prevention strategies, and early treatment of placental dysfunction as a result of pollution
exposures may be developed.
first trimester of pregnancy is a particularly vulnerable time period for the developing
fetus and a mother's exposure to air pollution may alter the way that the placenta is
established and how it functions throughout the rest of pregnancy. This project aims to
expand and develop new MRI technologies to assess real-time placental structure and function
as pregnancy develops from the first to the third trimester so that early detection,
prevention strategies, and early treatment of placental dysfunction as a result of pollution
exposures may be developed.
Many epidemiological studies have associated exposure to traffic-derived air pollution from
motor vehicles, air toxins from industry and other environmental toxins by pregnant women
with measures of poor birth outcomes including preeclampsia (PE), preterm birth (PTB) and
intra-uterine growth restriction (IUGR). Preeclampsia, preterm labor and IUGR, collectively
known as ischemic placental disease, are strongly correlated with infant morbidity and a host
of adult diseases ranging from coronary artery disease to cancer. Although it is widely
believed that the pathophysiological mechanisms leading to complications of ischemic
placental disease and placental insufficiency have similar biological origins, starting as
early as defective placental implantation, to date there are no predictive studies that
prospectively examine placental structure and/or function. This may be related to existing
technologies, routinely employed in clinical decision-making, such as ultrasonography and
certain biomarkers, lacking precision in the first trimester, and adequate sensitivity and
specificity in the second to third trimesters. Thus, assessment and prediction of normalcy
versus aberrancy of placental function are lacking. Therefore, the overarching objective of
this proposal is to develop and evaluate a suit of cutting-edge multi-parametric magnetic
resonance imaging (mp-MRI) technologies (primary predictor), and translate these novel
placental imaging modalities to assessing the impact of environmental pollution exposure on
prediction of the composite of placental aberrancy/insufficiency and related outcomes (PE,
PTB and IUGR) (primary outcome).
Our central hypothesis is that chronic exposure to high rates of environmental pollution,
independent of socio-economic status (SES), increases the risk of placental insufficiency due
to early gestational development of adverse placental structure/function as detected by
mp-MRI technological advances.
To test this hypothesis, our interdisciplinary research team at UCLA will first develop
non-contrast freebreathing placental mp-MRI, consisting of multi-delay pseudo-continuous
arterial spin labeling (pCASL) perfusion and high-resolution multi-contrast structural MRI,
which will provide reproducible measures of placental perfusion and tissue microstructure
(AIM 1). The novel mp-MRI techniques will be compared to the uterine artery Doppler
ultrasound through pregnancy and validated ultimately by the gold standard histological
pathology and vascularity of the post-parturient placenta (AIM 2). Lastly, the investigators
will perform in-depth analyses of recruited subjects for exposure to environmental pollution
and correlate their rates of exposure to extensively collected pregnancy outcomes, towards
building a predictive model (AIM 3). Our specific aims are:
AIM 1: Develop non-contrast free-breathing placental mp-MRI techniques that can
non-invasively characterize the in vivo placental perfusion and microstructure through all
trimesters.
A. Develop a free-breathing multi-delay pCASL sequence using background-suppressed
localized-volume 3D GRASE imaging for quantitative measurement of placental perfusion within
a 5-10 min scan (1.5x1.5x2 mm3 resolution).
B. Develop a free-breathing high-resolution golden-angle 3D stack-of-radial sequence with
self-navigation and retrospective motion compensation using compressed sensing for mapping
placental microstructure within a 5-10 min scan (1x1x1 mm3 isotropic resolution).
AIM 2: Evaluate placental mp-MRI by longitudinal comparison with uterine artery Doppler
ultrasound through gestation as a predictive marker of placental insufficiency.
A. Conduct a 3-year prospective cohort study of pregnant women, performing newly developed
mp-MRI (AIM1) in the 1st and 2nd trimesters in parallel to ultrasound measurement of uterine
artery Doppler, to assess mp-MRI prediction capability versus ultrasound.
B. Collect detailed pregnancy outcome data of prospective cohort, including diagnosis,
neonatal outcome, and placenta for pathological and histological analysis to ascertain risk
factors for placental insufficiency as a response to environmental exposures (AIM 3).
AIM 3: Perform in-depth analyses in recruited subjects to determine associations of
environmental pollution exposures and both placental mp-MRI measurements and concomitant
pregnancy outcomes.
A. Perform in-depth analyses to measures of modeled environmental pollution exposure in our
recruited subjects to assess associations with mp-MRI measures of placental structure and
perfusion throughout gestation, taking into account multiple confounding factors such as
maternal age at delivery, race/ethnicity, and SES.
B. Correlate mp-MRI measures of placental structure and perfusion throughout gestation with
pregnancy outcomes, post-parturient assessment of placental weight, pathology, and neonatal
outcomes. These studies will establish the impact of environmental pollution on placental
structure and function, and related pregnancy outcomes, with obstetric and neonatal practices
embracing surveillance tactics based on the residential location of pregnant women and their
offspring. In addition, the proposed research will establish the potential for early
recognition of placental insufficiency, thereby staging future strategies of preventive and
interventional therapies targeting reversal before encountering detrimental consequences.
motor vehicles, air toxins from industry and other environmental toxins by pregnant women
with measures of poor birth outcomes including preeclampsia (PE), preterm birth (PTB) and
intra-uterine growth restriction (IUGR). Preeclampsia, preterm labor and IUGR, collectively
known as ischemic placental disease, are strongly correlated with infant morbidity and a host
of adult diseases ranging from coronary artery disease to cancer. Although it is widely
believed that the pathophysiological mechanisms leading to complications of ischemic
placental disease and placental insufficiency have similar biological origins, starting as
early as defective placental implantation, to date there are no predictive studies that
prospectively examine placental structure and/or function. This may be related to existing
technologies, routinely employed in clinical decision-making, such as ultrasonography and
certain biomarkers, lacking precision in the first trimester, and adequate sensitivity and
specificity in the second to third trimesters. Thus, assessment and prediction of normalcy
versus aberrancy of placental function are lacking. Therefore, the overarching objective of
this proposal is to develop and evaluate a suit of cutting-edge multi-parametric magnetic
resonance imaging (mp-MRI) technologies (primary predictor), and translate these novel
placental imaging modalities to assessing the impact of environmental pollution exposure on
prediction of the composite of placental aberrancy/insufficiency and related outcomes (PE,
PTB and IUGR) (primary outcome).
Our central hypothesis is that chronic exposure to high rates of environmental pollution,
independent of socio-economic status (SES), increases the risk of placental insufficiency due
to early gestational development of adverse placental structure/function as detected by
mp-MRI technological advances.
To test this hypothesis, our interdisciplinary research team at UCLA will first develop
non-contrast freebreathing placental mp-MRI, consisting of multi-delay pseudo-continuous
arterial spin labeling (pCASL) perfusion and high-resolution multi-contrast structural MRI,
which will provide reproducible measures of placental perfusion and tissue microstructure
(AIM 1). The novel mp-MRI techniques will be compared to the uterine artery Doppler
ultrasound through pregnancy and validated ultimately by the gold standard histological
pathology and vascularity of the post-parturient placenta (AIM 2). Lastly, the investigators
will perform in-depth analyses of recruited subjects for exposure to environmental pollution
and correlate their rates of exposure to extensively collected pregnancy outcomes, towards
building a predictive model (AIM 3). Our specific aims are:
AIM 1: Develop non-contrast free-breathing placental mp-MRI techniques that can
non-invasively characterize the in vivo placental perfusion and microstructure through all
trimesters.
A. Develop a free-breathing multi-delay pCASL sequence using background-suppressed
localized-volume 3D GRASE imaging for quantitative measurement of placental perfusion within
a 5-10 min scan (1.5x1.5x2 mm3 resolution).
B. Develop a free-breathing high-resolution golden-angle 3D stack-of-radial sequence with
self-navigation and retrospective motion compensation using compressed sensing for mapping
placental microstructure within a 5-10 min scan (1x1x1 mm3 isotropic resolution).
AIM 2: Evaluate placental mp-MRI by longitudinal comparison with uterine artery Doppler
ultrasound through gestation as a predictive marker of placental insufficiency.
A. Conduct a 3-year prospective cohort study of pregnant women, performing newly developed
mp-MRI (AIM1) in the 1st and 2nd trimesters in parallel to ultrasound measurement of uterine
artery Doppler, to assess mp-MRI prediction capability versus ultrasound.
B. Collect detailed pregnancy outcome data of prospective cohort, including diagnosis,
neonatal outcome, and placenta for pathological and histological analysis to ascertain risk
factors for placental insufficiency as a response to environmental exposures (AIM 3).
AIM 3: Perform in-depth analyses in recruited subjects to determine associations of
environmental pollution exposures and both placental mp-MRI measurements and concomitant
pregnancy outcomes.
A. Perform in-depth analyses to measures of modeled environmental pollution exposure in our
recruited subjects to assess associations with mp-MRI measures of placental structure and
perfusion throughout gestation, taking into account multiple confounding factors such as
maternal age at delivery, race/ethnicity, and SES.
B. Correlate mp-MRI measures of placental structure and perfusion throughout gestation with
pregnancy outcomes, post-parturient assessment of placental weight, pathology, and neonatal
outcomes. These studies will establish the impact of environmental pollution on placental
structure and function, and related pregnancy outcomes, with obstetric and neonatal practices
embracing surveillance tactics based on the residential location of pregnant women and their
offspring. In addition, the proposed research will establish the potential for early
recognition of placental insufficiency, thereby staging future strategies of preventive and
interventional therapies targeting reversal before encountering detrimental consequences.
Inclusion Criteria:
- 18 years of age or older
- Planning to delivery at a UCLA hospital
- Carrying a viable pregnancy
- Not carrying multiple gestation
Exclusion Criteria:
- Known fetal chromosomal or structural abnormalities
- Contraindications to having MRI evaluation
- Inability to provide consent
We found this trial at
1
site
Los Angeles, California 90095
310-825-4321
Principal Investigator: Sherin Devaskar, MD
Phone: 310-825-5095
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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