Synopsis

The aim of this study was to investigate the functional characteristics of the human placenta ex-vivo using a novel MR compatible perfusion system. Fifteen normal human placentas were scanned ex-vivo; bolus arrival time (BAT) and flow were extracted from TWIST data. Higher BAT and lower flow values were found in placentas with peripheral cord insertion. Significant correlations were obtained between BAT and the linear distance of the blood vessel from cord insertion location. This is the first work that studied the perfusion of human placentas with MRI and provides information regarding the relation between placental structure and function.

Abstract

INTRODUCTION

Normal placental development and function are vitally important for healthy pregnancy and normal fetal development (1-6). There is strong evidence that many of the major complications of pregnancy have their roots in placental insufficiency. To date, the gold standard for in-vivo diagnosis of placental function is US Doppler, which gives only an indirect assessment. Several studies investigated human placental structure and function ex-vivo (7), yet understanding regarding human placental function and its association with its structure, pregnancy risks and outcomes is limited. The aim of this study was to investigate the functional characteristics of the normal human placenta ex-vivo using a novel MR compatible perfusion system and advanced MR methods implemented from the field of neuro-imaging.

METHODS

Placentas and MR protocol Fifteen normal placentas were obtained from donors who provided informed consent after full term pregnancies (38-41 weeks’ gestation), up to one hour after delivery of healthy newborns weighing between 2700 kg to 3900 kg. Placentas were rinsed with a solution of saline and heparin before being connected to an MR compatible perfusion system for ex-vivo imaging of human placenta, that mimics the pulsatile flow of the fetal cardiovascular system (Fig. 1). Dynamic time-resolved 3D magnetic resonance angiography (MRA) technique with Interleaved Stochastic Trajectories (TWIST) with high temporal (0.84 sec) and spatial resolution (0.937X0.937X1 mm) was used to capture the multiple arterial, mixed, venous phase images during the passage of a contrast agent through the vascular anatomy. A mixture of 3 ml water and 0.3 ml of contrast agent (Gadolinum Dotarem 0.5M) was injected through an access in the inflowing pipe to the placental arteries, 10-20 sec after the scan began. Image Analysis Image analysis was performed using Matlab, and included: Bolus arrival time (BAT) and flow calculation. The algorithm consisted of the following steps: (1) Data normalization according to baseline; (2) Threshold vascular tree segmentation by angiography mask creation; (3) Bolus arrival time (BAT) calculation and BAT maps creation; (4) Flow maps creation by Gaussian fitting to the intensity over time and dividing the area under curve by the full width in half maximum; (5) Normalized BAT and flow histograms were extracted for each placenta. Placental function was studied in relation to cord insertion location (distance from center in percentages), while referring to para-central cord insertion (cord insertion is more than 3cm from placental edges) vs. marginal/peripheral (cord insertion is less than 3cm from placental edges).

RESULTS

All 15 placentas were successfully perfused, scanned, and analyzed providing BAT and flow maps. Fig. 2 shows coronal minimum intensity projection (MIP) of the BAT map (A,B), and flow (C, D) of typical placentas one (A, C) with central cord insertion and one (B, D) with peripheral cord insertion. Significant correlations (mean r=0.81 p<0.01) were obtained within each placenta between BAT values and the distance of the blood vessel from cord insertion location. Higher values of BAT were obtained in placentas with peripheral (marginal) cord insertion compared to placentas with para-central cord insertion. This can be seen in the histogram of the values of BAT in the two groups of placentas (Fig. 3). Lower values of flow were obtained in placentas with peripheral (marginal) cord insertion compared to placentas with para-central cord insertion. This can be seen in the histogram of the values of flow in the two groups of placentas (Fig. 4).

SUMMARY

-This is the first study to investigate ex-vivo perfusion of the human placenta using MR compatible perfusion system.

-This study demonstrates the ability to quantitatively characterize flow pattern of the entire vascular tree of ex-vivo placentas post-partum.

-Preliminary results suggest significant differences in perfusion between normal placentas with para-central vs. peripheral cord insertion.

-Our current efforts are to study the correlation between placental function and structure, and to investigate conditions of placental insufficiency.

Acknowledgements

References

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