MARS: Magnetic Resonance Study: A Novel Assessment of Placental Function

Study Overview
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Brief Summary
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The objective of this study is to evaluate functional MRI as a tool to study placental transfer of oxygen and nutrients during the third trimester of pregnancy in obese women, women with pregestational diabetes and healthy low risk women without these conditions (controls). The investigators hypothesize that altered placental function, including diminished placental oxygenation and enhanced placental transport of lipids and metabolites will be seen in obese and pregestational diabetics as compared to controls.

Detailed Description
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In this study, we propose to utilize two novel and innovative non-invasive tools to measure placental oxygenation and lipid and nutrient transport in vivo in women who are obese (OB), have pregestational diabetes (DM) or have neither (controls). To evaluate differences in placental oxygenation, we propose to use Blood Oxygen Level Depending (BOLD) imaging, a method of functional magnetic resonance imaging, to measure tissue oxygenation in the placenta during the third trimester of pregnancy. To evaluate placental lipid and nutrient content, we propose to utilize Magnetic Resonance Spectroscopy (MRS), a novel and powerful tool to compare lipid and nutrient transport across the placenta among OB, DM and controls. To confirm in vivo BOLD and MRS findings, we will extensively evaluate the placental lipid content and lipid transport capability. Fatty acid transport protein-4 (FATP-4), one of 6 FATP proteins, is important for placental lipid accumulation, especially LC-PUFA21-24. Docosahexaenoic acid (DHA) is a crucial LC-PUFA for neurogenesis in early development18. Major facilitator super family domain containing MFSD2a is a lysophospholipid transporter required for DHA uptake in the brain and has been linked to placental DHA transfer. Lipid content of the placenta can be assessed by visualizing lipid droplets via perilipin 2, the most abundant structural protein on the surface of lipid droplets of adipocytes. We hypothesize that altered placental function including diminished placental oxygenation and abnormal placental transport of lipids and other metabolites will be seen in OB and DM women as compared to controls. We further hypothesize that ex vivo placental pathologic, histologic and immunohistochemistry characteristics will be associated with in vivo findings. Our findings from this pilot study have the potential to serve as the basis of a larger study to further evaluate the potential impact of BOLD and MRS technology on our understanding of placental lipid and oxygen transport among women with obesity and pregestational diabetes as compared to women without these conditions.

Official Title
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MARS: Magnetic Resonance Study: A Novel Assessment of Placental Function

Conditions
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Placenta Diseases

Intervention / Treatment
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* Diagnostic Test: functional MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: singleton pregnancy planned cesarean section Exclusion Criteria: non-English speaking fetal anomalies gestational diabetes mellitus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal weight<br>BMI 18.5-24.9 kg/m^2 low risk pregnancy | Diagnostic Test: functional MRI<br>* Participants will undergo a functional MRI using multiple imaging modalities.<br>|
| Pregestational diabetes mellitus<br>Type 1 or Type 2 diabetes mellitus diagnosed prior to the pregnancy or in the first trimester | Diagnostic Test: functional MRI<br>* Participants will undergo a functional MRI using multiple imaging modalities.<br>|
| Obese<br>Pre-pregnancy BMI ≥ 30.0 kg/m^2 | Diagnostic Test: functional MRI<br>* Participants will undergo a functional MRI using multiple imaging modalities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BOLD response level in the placenta | As measured by the change in MRI from baseline (room air) compared to hyperoxygenation (O2 facemask) in the central area of the placenta | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placenta ratio of oxygenated hemoglobin to deoxygenated hemoglobin | As measured on MRI during third trimester in the central area of the placenta | 1 day | 
| Placenta ratio of choline to lipid | As measured on MRI during third trimester in the central area of the placenta | 1 day |