Advanced MRI for Uteroplacental Flow, Perfusion, Oxygenation & Inflammation
Condition: Pregnancy; Obesity; Preeclampsia
MeSH terms: Pre-Eclampsia; Inflammation
Study type: Observational

Summary: 
      The purpose of the study is to develop advanced ultrasound (U/S) and Magnetic Resonance
      Imaging, known as MRI to study uteroplacental health. The goal of this study is to evaluate
      the blood and oxygen flow to the placenta using advanced U/S and MRI testing.
    

Detailed description: 
      Decreased uteroplacental perfusion is a recognized antecedent event in pregnancies that
      ultimately results in adverse outcomes like fetal growth restriction (FGR), preeclampsia (PE)
      and/or preterm birth. This concept is well supported clinically by identification of spiral
      artery vascular lesions called acute atherosis. Current literature suggests that these events
      occur very early which is why we are using multiple techniques related to flow at early time
      points. We are studying individuals with either poor maternal vascular response and/or
      inadequate spiral artery remodeling with resultant inadequate placentation will have a
      reduced uteroplacental perfusion. Given that the spiral arteries draw the vast majority of
      the blood flow in a gravid state, poor placentation would be reflected in the total
      uteroplacental blood flow (UPBF), and early detection would allow both design and then
      routine initiation of novel preventive therapies early in gestation to improve pregnancy
      outcome.

      The goal of this research is to develop an arsenal of advanced ultrasound (U/S) and magnetic
      resonance imaging (MRI) techniques that are compatible to be run simultaneously or
      sequentially to probe uteroplacental health and overcome the limitations posed by obesity and
      motion. While safety concerns remain with MRI, particularly in the first trimester, we will
      front-load developmental and optimization studies in primate models as "proof of principle"
      before translating to humans; this conservative approach is key to our achieving paradigm
      shifting outcomes. A pilot study was completed prior to the main study to evaluate U/S
      Doppler and 2D PC MRI for UPBF measures that including contributions from the ovarian
      arteries in addition to the uterine arteries. The pilot study is now complete as the pilot
      data was evaluated after the enrolled pilot subjects completed the U/S and 2D PC MRI visits.

      We are matching all imaging measures with clinical data and blood and urine sample post-hoc
      analyses for cytokines and tissue-specific metalloproteases, these correlations will further
      inform a differential diagnosis of distinct disease mechanisms that may otherwise show common
      imaging outcomes. At the end of the studies on both lean and obese women, we will inevitably
      have outcomes categorized as FGR, hypertensive and/or PE, perhaps preterm and/or rarely
      stillbirth outcomes. Using this combination of approaches we will determine: 1) an optimal
      combination of imaging methods that is practical and sufficiently safe to use in humans; 2)
      if new data so derived is informative beyond that currently available clinically; 3) at what
      point in gestation an abnormality may be detected by these new methods relative to current
      standard clinical measures and/or diagnoses; and 4) if imaging outcomes can predict specific
      complications, or only warn of a higher risk of general complications.

      The primary objective of the ferumoxytol research, conducted under the pending
      Investigational New Drug Application, is to demonstrate homing of macrophages in vivo in the
      decidua of pregnancies with reduced uteroplacental blood-flow and perfusion. The secondary
      objective is to develop a test of placenta function in on-going pregnancies in subjects with
      reduced uteroplacental blood flow and perfusion. To evaluate these objectives, subjects with
      and without reduced total uterine blood-flow and possible reduced placental perfusion will
      receive Ferumoxytol (Feraheme®) prior to dynamic sequences magnetic resonance.
    

Intervention name(s): Ultrasound Scan; MRI Scan; Ferumoxytol
Intervention type(s): Procedure; Procedure; Drug
Intervention description(s): The research exam is expected to take 30 minutes for blood flow assessments; MR imaging will take approximately 30 minutes.; A subset of subjects will complete MRI imaging with ferumoxytol as a contrast agent at the 24-28 week visit. A nurse will administer ferumoxytol in a hospital triage with pulse and blood pressure monitoring and fetal heart monitoring. The pharmacy will prepare the infusion and deliver to triage. Subjects will arrive at the obstetric triage unit for ferumoxytol injection three days prior to their scheduled ferumoxytol MRI study. In the triage, the nurse will obtain baseline vital signs and fetal heart rate. The IV Ferumoxytol infusion will be 30 minutes and atients will be monitored at 5 to 15-minute intervals. Three days after the ferumoxytol infusion, at 24-26 weeks gestation, subjects will have blood/urine collected, undergo a 30 minute ultrasound, a 30 minute MRI, an adverse event review, and medical record review. The MRI scanning procedure will be conducted at WIMR and will last approximately 30-60 minutes.
Other intervention name(s): Feraheme®
Intervention MeSH terms: Ferrosoferric Oxide
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant Women (<14 weeks gestation)