Detection of Placental Lesions in Fetal Growth Restriction

The PI of this project was:

This project was funded by: NIH

The term of this project was: April 2021 to May 2021

The number of subjects scanned during this project was: 5

The majority of pregnancy complications have their origins in vascular maladaptation resulting in reduced perfusion, and are commonly associated with altered uteroplacental inflammation, immune cell homing and/or activation, all of which are further exacerbated by the greater level of hypoxia at the maternal-fetal interface (MFI). Suboptimal placentation is often accompanied by FGR with or without hypertension. There is a clear need for non-invasive assessment of vascular function and inflammation at the MFI, including in early pregnancy to identify any of these developing pathophysiologic conditions before their clinical manifestation. With adverse pregnancy outcomes, inappropriate growth factor and/or cytokine profiles, whether of immune cell, placental or maternal (including vascular) origin, play roles in the development of these outcomes.

Underlying vascular deficits eventually lead to pathological findings in the placenta that include acute atherosis (vascular lesions), placental infarcts with fibrosis (white infarcts) or without fibrosis (red infarcts) and perivillous fibrin deposition. Placental infarcts are preceded by formation of intervillous clot formation. These placental lesions identified after delivery are similar in FGR and preeclampsia. Diagnosis of FGR at early stages of pregnancy, generally at or before 26 weeks gestation have higher likelihood of underlying genetic cause or fetal viral infection. Early FGR of genetic etiology may be characterized by congenital defects frequently detected by ultrasound. FGR or viral etiology may be characterized by intracranial or intraabdominal echogenecity. FGR diagnosed later in gestation is more likely to be due to placental lesions. However, such clinical diagnosis of FGR is in error 60% of the time. (Review of our own data here at UW-Unity Point Health-Meriter) Identifying the placental lesions and detecting macrophage recruitment at placental implantation site in the uterine wall will improve the accuracy of the diagnosis of FGR and is likely to provide information on immune activation, which will identify individuals who will subsequently develop preeclampsia.
Currently there are no reliable methods for identifying these lesions during pregnancy. Therefore, developing imaging methods for identifying placental lesions and macrophage recruitment during pregnancy in FGR would advance diagnostic methodology for both FGR and preeclampsia, which may potentially allow interventions in the future. Perivillous fibrin deposition is preceded by reduced intervillous blood flow and subsequently will alter intervillous flow patterns, to be detected by MRI. Extensive perivillous fibrin deposition with further reduction in blood flow would result in formation of intervillous clot. MRI has much higher degree of tissue resolution, which would allow us to detect intervillous clot formation, identify regional reduced placenta perfusion and decrease placental oxygenation (BOLD). We posit that MRI techniques can identify these lesions with high degree of resolution and hence accuracy.