PROJECT SUMMARY
The capacity of the placenta to supply oxygen and nutrients from the maternal circulation, and eliminate
waste products from the fetal circulation, is critical for fetal development and is dependent on adequate
maternal- and fetal-placental perfusion. The clinical benefits of developing noninvasive tools for the in vivo
assessment of placental function are tremendous. They include the proper diagnosis of placental insufficiency
as a cause of fetal growth restriction, and detection of decreased fetal oxygen availability, allowing delivery to
be expedited to prevent neurological damage. This proposal combines the strengths of two investigative teams
with complementary methodologies, and builds upon our prior placental Magnetic Resonance Imaging (MRI)
achievements. Specifically, our team’s use of the pregnant nonhuman primate (NHP) has allowed development
of spatial modelling methods of placental function integrating dynamic contrast enhanced (DCE) MRI for
validation of T2* relaxation mapping. Our team have also developed novel MR imaging and data modeling
methods with simultaneous diffusion-encoded (IVIM-DWI) and multiecho spin-echo acquisitions. Initial clinical
application of these methods showed the potential to separately interrogate the materno-placental and feto-
placental circulations – this is a critical marker for identifying fetal hypoxia. The overall objective of this
proposal is to develop multi-modal MRI and modelling approaches, validated in a clinically relevant NHP
model, to provide robust quantitative methods for assessing placental health.
The significance of our work derives from combining data generated from multiple contrast techniques that
provide estimates of placental perfusion and oxygen saturation, with gold-standard measurement of oxygen
level in the fetus and post-delivery measurement of the placental vascular structure in our translational NHP
model. By leveraging established and new computational modeling of placental blood flow and function, our
unique combination of advanced methods and rich data will let us measure the properties of oxygen transfer to
the fetal vasculature (Aim 1). The physiological interpretation of these quantitative parameters will be further
validated in studies subject to controlled changes in maternal oxygenation accompanied by measurement of
fetal oxygenation (Aim 2). The combination of these methodologies will allow us to quantify and validate the
variables that are of most interest to human placenta oxygen perfusion and transport over a range of relevant
fetal oxygen levels. The validation of our modeling methods will significantly improve the discriminatory power
of MRI in stratifying pregnancies where placental insufficiency and fetal hypoxia is suspected. Importantly, we
have acquired preliminary data in our NHP model that demonstrates the feasibility of the approach we are
proposing. Successful completion of the intended work will yield a set of novel non-contrast functional and
structural MRI placental summary statistics, validated in an appropriate animal model, which can be translated
to human studies for early identification of pregnancies at-risk for complications.
