Penny Gowland1, Amy Turnbull1, George Hutchinson1, Louise Dewick2, Ruizhe Li3, Chris Bradley1,4, Xin Chen3, Grazziela Figueredo3, Simon Stockwell5, Divya Ramesh1, Neele Dellschaft1, Kate Walker2, and Nia Jones2
1Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, 2School of Medicine, University of Nottingham, Nottingham, United Kingdom, 3School of Computer Science, University of Nottingham, Nottingham, United Kingdom, 4National Institute for Health Research, Biomedical Research Centre, Hospital NHS Trust and University of Nottingham, Nottingham, United Kingdom, 5Faculty of Engineering, University of Nottingham, Nottingham, United Kingdom
Synopsis
Keywords: Placenta, Placenta
Motivation: We have previously observed placental contractions and now want to charcterise them further.
Goal(s): To characterise placental contractions (frequency, amplitude and length) in normal pregnancy.
Approach: Dynamic respiratory gated multislice EPI scans acquired for 30 minutes across the pregnant uterus, analyzed by automatic segmentation.
Results: Placental contractions lasting several minutes and sometimes causing very large changes in placental volume, were found in every woman studied.
Impact: Further work will investigate the function of contractions
and whether they are altered in compromised pregnancies.
Introduction
We recently observed the new phenomenon of placental
contractions in utero [1] distinct from uterine (Braxon Hicks) contractions,
although this contractile function had previously been postulated in the biology
literature [2]. However, since placental contractions are not periodic, we were unable to
determine how frequently they occurred. This study involves scanning healthy
pregnant women for about 30 minutes to characterise placental contractions
using automatic segmentation of the images. Method
Ethics approval was obtained from a
regional ethics committee. 10 women with healthy pregnancies (gestational ages
shown in Figure 1) were consented and scanned once, with a left lateral tilt in
a 3T Philips Ingenia scanner limited to normal operating mode. Dynamic
MRI was acquired for up to 30 minutes using multislice (NSL=32) single shot EPI
(TE 25ms, voxel 1.56x1.56x4 mm3,
FOV 400x400x316mm3
Sense 3), gated to the maternal breathing (minimum TR of 9s). The
flip angle was adjusted to maximize signal in the placenta (usually 110o).
Images were segmented to outline the uterine sac and
placenta (Figure 2).
This was done manually for some slices/volumes of all subjects, and also using
a convolutional neural network method,
known as nnunet [3]. The model was pre-trained on a different manually
segmented dataset [1] and refined on manually segmented data from this study.
Due to the current scarcity of 3D masks, the model was trained and validated on
2D slices. At this initial stage the segmentation results were post-processed
by discarding small mis-segmented regions (end slices) while retaining slices
with the largest contiguous regions for each of the two classes (slices missed indicated
in Figure 1).
The volume of the placenta, and area of placental bed and
remainder of the uterine wall were plotted against time (Figure 3). Placental
contractions were defined as a decrease in placental bed area of 10% below
current baseline with a concomitant increase in area of the rest of the uterine
wall, lasting more than two time points.
Cine images (Figure 4&5) were visually inspected for apparent maternal
motion, fetal movements that distorted the placenta, and uterine and placental
contractions (crosses in Figure 2). Placental contractions appeared as a
shortening and change in shape of the placenta. Uterine contractions were
defined as either (1) extensive wall thickening usually localised to one area
of the uterus not under placental bed or (2) changes in shape of the uterus.
Dynamic
susceptibility maps have been produced from this data for some subjects at this
stage (Figure 6).Results
Figure
4&5 shows gifs of two placental contractions. The segmentation model
underwent a 5-fold cross-validation on the 10 4D datasets, with each fold
encompassing 2 subjects. For each subject, the evaluation was conducted on the
annotated 2D slices. The averaged Dice coefficients between prediction and
ground truth are in Figure
1 (green columns).
Figure
3 plots the variations volume and surface area of the uterus, area of the
placental bed, volume of placenta, and average placental T2*wt BOLD signal. Figure 1 summarizes the
results obtained from viewing the cine image (pink columns) and from the time
courses in Figure 3
(blue columns). Apparent uterine contractions were observed later in pregnancy in
this group.
Figure
6 shows the signal time course for mean and standard deviation of BOLD and
susceptibility for the same two subjects. Discussion
Placental contractions lasting several minutes and sometimes
causing very large changes in placental volume, were found in every woman
studied. In half the women contractions occurred repeatedly, and the other half
showed periods of no contractions.
Similar numbers of
contractions were identified from inspecting the segmentation graphs and the
cine images. Automatic segmentation generally achieved acceptable results but did
not always preserve consistent anatomical structure and often failed in end
slices (less represented in training data). In future, we aim to leverage the
unique attributes of 4D datasets and incorporate an image alignment method to retain
geometrical information across time points, thereby improving segmentation
performance.
In future we will develop
methods for automatically detect placental and uterine contractions from the time
series of signals, areas and volumes (Figure 3) and images.
We also plan to
investigate the function of placental contractions. The BOLD signal generally decreases
during and after contractions. For the limited number of susceptibility maps
produced so far, the mean susceptibility is variable but the standard deviation
of susceptibility increases following a contraction (Figure 6). Together these early results might
indicate a reduction in blood oxygenation, a mismatch in oxygenation between
compartments and/or increased variability within the placenta. We will investigate
this further including with mathematical placental models.Acknowledgements
This work was funded by the Wellcome Leap In Utero Program. References
[1] Dellschaft, N.S., Hutchinson, G., Shah, S., Jones, N.W.,
Bradley, C., Leach, L., Pratt., Bowtell, R., Gowland P., The haemodynamics of
the uman placental in utero, P PLOS Biology 18(5): e3000676, 2020.
[2] Kato, Y., Oyen, M.L., and Burton, G.J. Villous tree
model with active contractions for estimating blood flow conditions in the
human placenta. Open Biomed Eng J, 11, 36-48m 2017.
[3] Isensee, F., Jaeger, P. F., Kohl, S. A., Petersen, J.,
& Maier-Hein, K. H. (2021). nnU-Net: a self-configuring method for deep
learning-based biomedical image segmentation. Nature methods, 18(2), 203-211.