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Movement of blood within the placenta
Simon Shah1, Nia Jones2, Lucy Edwards1, Richard Bowtell1, and Penny Gowland1,3

1Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, Nottingham, United Kingdom, 2Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Nottingham, United Kingdom, 3Nottingham University Hospitals NHS Trust and University of Nottingham, NIHR Nottingham Biomedical Research Centre, Nottingham, United Kingdom

Synopsis

Healthy placental function requires optimum percolation of blood throughout the intervillous space to provide adequate feto-maternal exchange. This depends on blood flow from the spiral arteries and permeability of the intervillous space - both being altered in conditions leading to fetal growth restriction. This study explores the use of diffusion based MRI to visualise and depict the blood flow within the placenta and explore the underlying micro-structure, including the repeatability of the measures.

Introduction

Healthy placental function requires optimum percolation of blood throughout the intervillous space to enable adequate transfer of gases, nutrients and waste products between the fetus and mother. This percolation depends on the flow of blood from the spiral arteries and the permeability of the intervillous space - both parameters that are altered in conditions leading to fetal growth restriction. Placental perfusion has previously been assessed using ASL1, IVIM2 and power Doppler ultrasound3. However we are not aware of any reported measures of net blood flow velocity within the placenta, which is a key measure for modelling blood flow through the intervillous space.

Aim

To measure coherent maternal blood flow within the placenta and identify its relationship to incoherent blood movement.

Methods

Scanning: 7 normal women (27-36 weeks gestational age [GA]) were recruited with local ethics committee approval. They were scanned on a 3T Philips Ingenia with a torso coil at SAR<2.0W/kg, in the left or right decubitus position4. Two subjects where discarded due to gross motion and low signal (posterior placentas).

IVIM measurements were acquired using single-shot, respiratory-gated, pulsed gradient spin echo (PGSE), EPI: TE/TR 61ms/1.8s, diffusion weighting b=0,1,3,9,18,32,54,88,147,200,350,400,500s/mm2, 5 transaxial slices, resolution 2.5x2.5x6mm3, repeated twice. The signal from high b values (b=88-500s/mm2) was smoothed before fitting for diffusion coefficient (D). Next unsmoothed signals S(b) were fitted to the IVIM model:

$$ S(b) = S_{0} [(1 - f_{IVIM})e^{-bD} + f_{IVIM}e^{-bD*}] $$

where D was fixed at the value obtained from the fit of high b values, S0 was the signal with no diffusion weighting, fIVIM represents the moving blood volume fraction, D* was the pseudo diffusion coefficient.

Kurtosis5 (K) The unsmoothed data were also fitted to:

$$ S(b) = S_{0} [(1 - f_{IVIM})e^{-bD + \frac{1}{6}b^{2}D^{2}K} + f_{IVIM}e^{-bD*}] $$

Velocity was measured in three orthogonal directions using another PGSE sequence[6] repeated twice, and was calculated from:

$$ v_{x,y,z} =\dfrac{ \Delta\phi}{\gamma G_{x,y,z} T \Delta} $$

where ΔΦ was the net phase accumulated due to the diffusion gradients, Gx,y,z=21.6mT/m was gradient amplitude, $$$Δ$$$=15.9ms was lobe length and T=31.3ms was time between lobes.

Results

Fig.2 shows velocity, f­IVIM and kurtosis for one subject. Flow into the placenta was observed on the maternal side and was in the opposite direction on the fetal side. The maximum net flow velocity was ~0.1cm/s. Fig.1 (overlay) indicates the relationship between regions of high vflow, f­IVIM and kurtosis. Fast flow (green, yellow) occured at the edge of the placenta, with high f­IVIM regions overlapping (yellow) or occuring more centrally (green). High kurtosis occurred in areas of low f­IVIM and slow vflow (blue, little magenta or turquoise).

Fig.3 shows velocity histograms with a normal distribution fitted to the central peak. The box-plots show velocities above and below the 95th centile of the fitted peak. Forward and backward velocities were similar, but were higher in the basal plate than the placenta (P<0.0001 Mann Whitney test, each direction separately). Fig.4 shows example histograms and box-plots of f­IVIM. f­IVIM was significantly higher in the uterine wall and basal plate than the placenta (p=0.004 and 0.02 paired t-test).

Fig.5 indicates repeatability comparing data from two scans collected on each subject and example decay curves from two placental ROIs.

Discussion

This work measured coherent flow velocities within the placenta for the first time, and compared it to fIVIM and kurtosis, interpreted as blood percolating through the villous tree with large or small mean free paths respectively. Net flow near the basal plate is consistent with flow from the spiral arteries, and net negative flow on the fetal side suggests that deoxygenated blood is pooling between the villous trees. We are not sensitive to fetal flow in the villous trees at this spatial resolution.

vflow and fIVIM were higher in the basal plate than the placenta in all subjects (except vflow in Sub.1’s basal plate). The overlay maps indicate spatial correspondence between areas of high vflow and high fIVIM. Areas with lower vflow or fIVIM corresponded to areas of high kurtosis probably related to slow percolation away from the spiral arteries.

Sub.1 (earlier gestational age and experiencing uterine contractions) showed slow placental flow and low basal plate f­IVIM (data sets acquired independently) but the placental flows and fIVIM were unchanged. The data showed good agreement between repeated measurements.

Conclusion

We have measured flow velocities in the placenta and related them to IVIM and kurtosis. These results will depend on the scan parameters (voxel size and echo time). The analysis is now being extended to compare MR signals to more physical models of placental flow.

Acknowledgements

This work was funded by the NIH-funded Placenta imaging Project: 1U01HD087202-01

References

[1] Gowland, P. A., Francis, S. T., Duncan, K. R., Freeman, A. J., Issa, B., Moore, R. J., Bowtell, R. W., Baker, P. N., Johnson, I. R. and Worthington, B. S. (1998), In vivo perfusion measurements in the human placenta using echo planar imaging at 0.5 T. Magn. Reson. Med., 40: 467–473.

[2] Moore, R. J., Strachan, B. K., Tyler, D. J., Duncan, K. R., Baker, P. N., Worthington, B. S., Johnson, I. R. & Gowland, P. A. In utero perfusing fraction maps in normal and growth restricted pregnancy measured using IVIM echo-planar MRI. Placenta 21, 726–732 (2000).

[3] Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Threedimensional power Doppler sonography: imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol 1999; 14: 139–143.

[4] Kerr MG, Scott DB, Samuel E. Studies of the Inferior Vena Cava in Late Pregnancy. Br Med J (Clin Res Ed). Feb 29; 1964 1(5382):522, 524–533.

[5] Jens H. Jensen, Joseph A. Helpern, Anita Ramani, Hanzhang Lu, and Kyle Kaczynski Diffusional Kurtosis Imaging: The Quantification of Non Gaussian Water Diffusion by Means of Magnetic Resonance Imaging, Magnetic Resonance in Medicine 53:1432–1440 (2005)

[6] Stejskal EO, Tanner JE. Spin diffusion measurements: spin echoes in the presence of a time‐dependent field gradient. The journal of chemical physics. 1965 Jan 1;42(1):288-92.

Figures

Figure 1: Schematic of the structure and function of the human placenta: (a) The structure of the villous tree within the placenta. (b) The fetal blood circulation and oxygenation exchange within the villi. (c) The circulation and (d) the pathway of percolating maternal blood in the intervillious space. (e) and (f) are the basal and chorionic plates respectively. (h) and (i) are the umbilical vein and arteries respectively. [Adapted from Carlson BM (ed): Human Embryology and Developmental Biology. Philadelphia, Elsevier Ltd., 2004.]

Figure 2: Velocity maps in the three orthogonal transverse, longitudinal and axial directions of the placenta and the averaged vector magnitude velocity map in cm/s, found by taking the vector norm of the velocities in the 3 directions (top row). fIVIM and kurtosis (K) maps with the placenta outlined in black (bottom row). Overlay depicts the regions in the placenta where the upper percentiles of fIVIM, vflow and K fall.

Figure 3: Example histograms of the velocities in the three orthogonal planes, with a normal distribution fitted to the central peak (inset the positive and negative directions along with the vflow maps to highlight the direction of blood flow). Boxplots for the 5 subjects (with GAs) for the placenta and basal plate.

Figure 4: Example histogram of the distribution of fIVIM in the placenta, wall, basal and chorionic plates. Boxplots of the 5 subjects in increasing GA are shown and indicate that the wall and basal plate have the higher fIVIM

Figure 5: The repeatability of the fIVIM and vflow maps, from the separate repeated scans. The boxplots shows how fIVIM varies in repeated scans for all 5 subjects

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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