Murine placenta is a complex organ, consisting of different cell compartments that vastly influence its blood-flow pattern. Dynamic contrast enhanced (DCE) MRI of murine placental perfusion was reported using low and high MW contrast media. Low-MW gadolinium chelates can cross the placenta and reach the fetal blood-pool . In this study, we used high-MW, albumin-based macromolecular contrast agent that does not cross the placental barrier, but is actively internalized by trophoblast cells in the labyrinth [2, 3]. To interpret the observed data, we suggest a novel model for describing Feto-maternal processing of labeled- albumin in placental DCE-MRI experiments.
MRI was performed on B6 (C57BL/6J) female mice on E14.5 (n=7) of gestation, using a 9.4 T Bruker scanner. T1-weighted 3D-GE images were acquired during a 60 min period immediately following contrast-agent (biotin-BSA-Gd-DTPA) administration. The mean signal intensity (SI) was derived for each placenta and for the vena cava. 3D rendering was performed using Amira display software. Histological validation was performed by Avidin-FITC labeling of the biotin-conjugated contrast agent. A three-compartment model with two main placental compartments — maternal intravascular compartment and trophoblast cell intracellular compartment — in addition to the maternal arterial input was suggested for SI interpretation and dynamic calculation [Fig.1 A].
Contrast-agent administration produced an initial SI increase during the 3-9 min following contrast-agent injection, which was followed by SI decrease (12-27 min) and then a second SI recovery 30-60 min post injection [Fig.1B-C]. Histological validation suggests contrast-agent accumulation with time, and active internalization by trophoblast giant cells, as well as syncytiotrophoblasts, in the labyrinth [Fig.1E].
The SI reduction and subsequent SI recovery, together with the histological validation of contrast-agent gradual accumulation, reinforces the hypothesis of active uptake that generates a T2* effect (signal reduction). The dynamics of the albumin-based contrast media internalization are superimposed on a gradual accumulation of contrast media in the large maternal placental blood pool [Fig.1 A, C]. This model study reveals complex and unexplored placental functionality in fetal recycling of maternal albumin.
Suggested three-compartment model for biotin-BSA-Gd-DTPA kinetics during DCE-MRI scanning of mouse placenta.
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Lysenko M, Avni R, Biton EI, Dafni H, Edrei Y, Garbow JR, Neeman M
The Weizmann Institute, Rehovot