The murine placenta is a complex organ, consisting of different cell compartments that greatly influence its blood-flow pattern. Dynamic contrast enhanced (DCE) MRI of murine placental perfusion has been reported previously using both low and high MW contrast media. Low-MW gadolinium chelates can cross the placenta and reach the fetal blood-pool [1]. In this study, we used high-MW, albumin-based macromolecular contrast agent that does not cross the placental barrier, but, instead, forms contrast-based aggregates that accumulate in the maternal vasculature simultaneously with active contrast internalization by trophoblast cells in the labyrinth [2, 3]. To interpret the observed data, we suggest a novel model for describing feto-maternal processing and aggregate formation of labeled albumin in placental DCE-MRI experiments.Animal experiments were approved by the animal care committee. MRI experiments were performed on B6 (C57BL/6J) female mice on E14.5 (n=5) 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 [Fig.1 A, P=Placentae, E=Embryonic sack]. The mean signal intensity (SI) was calculated for each placenta. 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 – combined with contrast-based aggregate formation and dispersion kinetics was developed for SI interpretation and T2 map calculations.Contrast-agent administration produced an initial SI increase during the 3-9 min following contrast-agent injection, which was followed by SI decrease (10-29 min) and then a second SI increase (recovery) 30-60 min post injection [Fig.1 B-C]. Histological analysis suggests aggregate accumulation in the maternal compartment during the initial SI increase, achieving its maximal level during the SI reduction stage [Fig.1 D, L; Labyrinth]. Dispersion of aggregates was observed during the SI recovery stage [Fig.1 E, white arrows]. T2 maps of the aggregates demonstrate a homogeneous T2 effect during SI elevation stage [Fig.1 F, Lab; Labyrinth, Dec; Decidua]; while a heterogeneous and localized T2 effect was observed in the SI reduction and recovery stages. Shorter T2 values were observed in the decidual maternal placental area during SI reduction [Fig.1 G], whereas shorter T2 values were observed in the labyrinth zone, which is mainly composed of trophoblast cells, during the SI recovery stage [Fig.1 H].The observed SI pattern, together with the histological validation of contrast-agent aggregation during SI reduction stage and its dispersion during SI recovery, suggest that the major portion of the signal reduction is caused by contrast-based aggregation ,which result with T2 shortening effect. The dynamics of the albumin-based contrast media aggregation and its internalization by trophoblast cells are superimposed on a gradual accumulation of contrast media in the large, maternal placental blood pool. Both T2 mapping and DCE-MRI images illustrate signal reduction directionality, with effects initiating from the outer, maternal intravascular compartment, and propagating toward the intracellular compartments in the labyrinth zone of the placenta. This study reveals unexplored and complex in vivo system for non-invasive study of the assembly and dispersion kinetics of aggregate forming compounds and sheds light on the functionality and structure of different placental compartments.