Advanced MRI for Uteroplacental Flow, Perfusion, Oxygenation & Inflammation

Decreased uteroplacental perfusion is a recognized antecedent event in pregnancies that
ultimately result in adverse outcomes like fetal growth restriction, preeclampsia 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 the investigators propose imaging using multiple techniques related
to flow at early time points. The investigators propose that 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, 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, the
investigators 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 will be completed prior to the main study
to evaluate U/S Doppler and two dimensional phase contrast (2D PC) MRI for Uteroplacental
Blood Flow (UPBF) measures that including contributions from the ovarian arteries in addition
to the uterine arteries.

The investigators will match 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, the study team will inevitably have
outcomes categorized as Fetal Growth Restriction (FGR), hypertensive and/or preeclampsia
(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; 4) If
imaging outcomes can predict specific complications, or only warn of a higher risk of general
complications.

Subject Population (Pilot study)

Inclusion Criteria:

1. Women with singleton, low-risk pregnancies

2. Gravida 1 (first pregnancy); or Gravida 2 (second pregnancy with first pregnancy
carried to term or miscarried prior to 14 weeks or terminated); or Gravida 3 (third
pregnancy with first and second pregnancies carried to term or one previous pregnancy
carried to term and the other previous pregnancy miscarried prior to 14 weeks or
terminated)

3. Ultrasound confirmed pregnancy dating prior to 14 weeks gestation

4. Non-obese (BMI 18.5-29.9 kg/M2) or Obese (Class I BMI 30-34.9 kg/M2 or Class II BMI
35-39.9 kg/M2) based on pregravid BMI

Exclusion Criteria:

1. Known fetal chromosome abnormality, structural malformation or syndromes in current
pregnancy

2. Tobacco or alcohol or drug use in current pregnancy

3. Pre-existing autoimmune conditions or other maternal chronic diseases like renal
diseases, chronic hypertension, thrombophilia, type I or II diabetes or any
vasculopathy

4. History of sickle cell anemia or sickle cell trait

5. High risk for gestational hypertension, pre-eclampsia, HELLP syndrome, fetal growth
restriction (FGR), abruptio placentae secondary to hypertension or pre-eclampsia,
stillbirth/intrauterine fetal death

Subject Population (Main study) Inclusion Criteria

Control Group:

1. Non-obese (pregravid BMI 18.5-29.9 Kg/M2)25 (N=80)

2. Women with singleton, low-risk pregnancies

3. Gravida 1 (first pregnancy); or Gravida 2 (second pregnancy with first pregnancy
carried to term or miscarried prior to 14 weeks or terminated); or Gravida 3 (third
pregnancy with first and second pregnancies carried to term or one previous pregnancy
carried to term and the other previous pregnancy miscarried prior to 14 weeks or
terminated)

4. Ultrasound-confirmed pregnancy dating prior to 14 weeks gestation

5. Gestational age at screening prior to 16 weeks

Study Group:

1. Obese (pregravid Class I BMI 30-34.9 kg/M2 or pregravid Class II BMI 35-39.9 kg/M2)
(N=80)

2. Women with singleton, low-risk pregnancies

3. Gravida 1 (first pregnancy); or Gravida 2 (second pregnancy with first pregnancy
carried to term or miscarried prior to 14 weeks or terminated); or Gravida 3 (third
pregnancy with first and second pregnancies carried to term or one previous pregnancy
carried to term and the other previous pregnancy miscarried prior to 14 weeks or
terminated)

4. Ultrasound confirmed pregnancy dating prior to 14 weeks gestation

5. Gestational age at screening prior to 16 weeks

Exclusion Criteria

Control and Study Groups:

1. Known fetal chromosome abnormality, structural malformation or syndromes in current
pregnancy

2. Tobacco/alcohol/drug use in current pregnancy

3. Pre-existing autoimmune conditions or other maternal chronic diseases like renal
diseases, chronic hypertension, thrombophilia, type I or II diabetes or any
vasculopathy

4. History of sickle cell anemia or sickle cell trait

5. High risk for gestational hypertension, pre-eclampsia, HELLP syndrome, fetal growth
restriction (FGR), abruptio placentae secondary to hypertension or pre-eclampsia,
stillbirth/intrauterine fetal death

a. The determination of whether or not the subjects are considered high risk for the
conditions described above will be based on medical and obstetrical history review by
clinical investigators with expertise in Maternal Fetal Medicine.

6. Contraindications to MRI (such as claustrophobia, metallic implant, etc.) based on MRI
Screening

7. Participation in other interventional clinical trials, including those with other
investigational agents not included in this trial, within 30 days of the start of this
trial and throughout the duration of this trial

8. Any physical or psychological symptom, based on the clinical judgment of the study
physician that would make a participant unsuitable for the study.