Vidya Rajagopalan1,2, Vince Schmithorst, Julie Coloigner, Jessica Wisnowski, Matthew Borzage, Hollie Lai, Skorn Ponrartana, Ashok Panigrahy, and Stefan Bluml
1Children's Hospital Los Angeles, Los Angeles, CA, United States, 2Rudi Schulte Research Institute
Synopsis
We present here, for the first time, parametric maps of oxygen activity in normal human placenta using in utero functional MR imaging. Our method highlights anatomical and gestational age dependent patterns in placental activity. These maps can be used to gain insight into normative placental function and identifying insufficient or abnormal placental functioning at various points in gestation.
Introduction
Our current
understanding of placental development and function is based on animal
imaging [4] and ex-vivo studies of placenta obtained after delivery or
interrupted pregnancies. Previous human imaging studies were restricted to
understanding hyperoxygentation[1,2] or adverse developmental conditions
such as fetal growth restriction (FGR), placental previa, placenta accrete, etc. [5]. These studies strongly indicate that
improved in-vivo delineation of
vasculogenesis and angiogenesis of
the placenta has the potential to provide better insight into the
pathogenesis of placental dysfunction. By leveraging non-invasive,
high-resolution imaging capabilities of in utero fetal MRI, we present a spatiotemporal analysis of
normative fetoplacental oxygenation patterns at various time points in
gestation. We hypothesize that (a)
spatial variance of BOLD placental signal would age-dependent , and (b) that serial parametric maps of BOLD
signal would reveal important anatomic insights about the feto-placental
and maternal circulation.Methods
We
conducted a prospective two-site study of placental development in which 20 maternal subjects with normal pregnancies were recruited between 26- 37 gestational weeks (GW). Images were acquired using 3T Philips Ingenia or Siemens Skyra machines. Over a 5- 10 minute total acquisition time,
BOLD images (1.5 mm x 1.5 mm x 4 mm) were acquired using an EPI sequence
in blocks of 60 images with TR/TE = 3000/35 ms, flip angle = 90°. In
addition, a high resolution T2 weighted images (1 mm x 1 mm x 3 mm) were
acquired using a 3D FFE sequence (TR/TE = 3.1/1.6 ms, flip angle = 75°).
BOLD images were processed using the "Functional MRI of
the Brain" Software Library (FSL) [6]. The BOLD signal was motion
corrected, coregistered to the T2 images and filtered to remove physiological
noise such as cardiac, breathing and metabolic fluctuations. An F test was used to test the relationship between spatial signal variations and gestational age. To compare oxygenation levels within the
placenta, we computed the normalized BOLD values after averaging the amplitude
of the BOLD signal over the duration of the study for each time point. Results
We found that the spatial variance of the BOLD signal was age dependent (F= 2.25,
p<0.001). We then generated parametric maps of oxygen activity in a subset of
fetuses at various gestational ages. Figure 1 shows the mean BOLD signal values
across the placenta between 26 and 36 GW. The parametric mapping delineates two distinct
regions of high oxygenation activity, corresponding to the fetal side (adjacent
to the site of umbilical cord attachment) and the maternal side (along the
uterine wall). The regions of high activity also occurred in specific clusters.
The size and number if these high-activity regions increased from 26 to 28 GW. We
then observed a drop in the number and size of these regions at 29 GW with a further decrease at 36 GW.Discussion
Our results clearly indicate that oxygenation is
spatially heterogenous across the placenta with oxygen activity concentrated at
specific anatomical locations. The spatial variance in oxygen activity is also
age-dependent. The reduction in size and number of high activity clusters at
29 GW and beyond correlates with the involution of the placenta in the third
trimester leading to birth [3]. Lower BOLD signal values in the middle of the
placenta could correspond to the lack of deoxyhemoglobin as these regions only
transport oxygen to the umbilical cord [7]. The oxygenation maps provide a baseline for how
oxygen activity occurs and changes over gestation giving us a better
understanding of fetoplacental haemodynamics and placental transfer. They may also be used to identify abnormal
oxygenation patterns in a placenta thereby acting as a marker for early
detection of FGR or insufficient placental function.
Conclusion
There
are age-dependent, spatial variances of BOLD signal in the placenta which
may correlate with angiogenesis. Using parametric mapping of placental BOLD signal, we have demonstrated that placental oxygenation activity is concentrated at specific anatomical locations associated with feto-maternal oxygen exchange. The non-invasive and repeatable methods
presented here may facilitate better predictions of placental dysfunction in high-risk pregnancies and inform perinatal care.
Acknowledgements
No acknowledgement found.References
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