Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model

Andrew A Badachhape,Ananth V Annapragada,Eric A Tanifum,Ketan B Ghaghada,Karin A Fox,Laxman Devkota,Poonam Sarkar,Chandrasekhar Yallampalli,Igor V Stupin,Mayank Srivastava

doi:10.1038/s41598-019-55019-8

Andrew A Badachhape, Ananth V Annapragada + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-55019-8

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Abstract

Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest for characterization of vascular perfusion in placentae during pregnancy to identify placental insufficiency that may be indicative of local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI) may enable direct placental FBV estimation and may provide a reliable, 3D alternative to assess maternal-side placental perfusion. In this pre-clinical study, we investigated if placental FBV at 14, 16, and 18 days of gestation could be estimated through contrast-enhanced MRI using a long circulating blood-pool liposomal gadolinium contrast agent that does not penetrate the placental barrier. Placental FBV estimates of 0.47 ± 0.06 (E14.5), 0.50 ± 0.04 (E16.5), and 0.52 ± 0.04 (E18.5) were found through fitting pre-contrast and post-contrast T1 values in placental tissue using a variable flip angle method. MRI-derived placental FBV was validated against nanoparticle contrast-enhanced computed tomography (CE-CT) derived placental FBV, where signal is directly proportional to the concentration of iodine contrast agent. The results demonstrate successful estimation of the placental FBV, with values statistically indistinguishable from the CT derived values.

Highlights

The placenta is a critical organ for nutrient transportation and oxygen exchange between fetal and maternal systems
The high T1 relaxivity of the liposomal-Gd contrast agent resulted in shortened T1 relaxation times in placental tissue and large blood vessels such as the inferior vena cava (IVC)
Mean placental fractional blood volume (FBV) estimates derived from contrast-enhanced T1-mapping showed close agreement with paired estimates from contrast-enhanced Computed tomography (CT)

Summary

Introduction

The placenta is a critical organ for nutrient transportation and oxygen exchange between fetal and maternal systems. Impedance of blood flow in the placenta is a critical factor in determining the rate of transplacental exchange and is often assessed indirectly through indices of placental flow in the umbilical artery. Indices such as the umbilical artery systolic-to-diastiolic ratio, resistance index, or pulsatility index may be measured through frequency-based color Doppler ultrasound[4,5,6,7]. Placental FBV measured using MRI and a blood-pool contrast agent should provide accurate estimates of perfusion by calculation of placental signal enhancement compared to that of a fully vascularized compartment As this can be performed non-invasively, CE-MRI provides a unique window into understanding placental function even in early pregnancy and following the natural history to delivery. We anticipate that use of CE-MRI to detect decreased placental FBV prior to the onset of fetal growth restriction may help guide clinicians in counseling patients and in managing high-risk pregnancies

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