Ferumoxytol dynamic contrast enhanced magnetic resonance imaging identifies altered placental cotyledon perfusion in rhesus macaques

Author:

Seiter Daniel P1,Nguyen Sydney M234,Morgan Terry K5,Mao Lu6,Dudley Dawn M7,O’connor David H37,Murphy Megan E234,Ludwig Kai D1,Chen Ruiming1,Dhyani Archana8,Zhu Ante910,Schotzko Michele L3,Brunner Kevin G3,Shah Dinesh M4,Johnson Kevin M110,Golos Thaddeus G234,Wieben Oliver110

Affiliation:

1. Department of Medical Physics, University of Wisconsin-Madison , Madison, WI , USA

2. Department of Comparative Biosciences, University of Wisconsin-Madison , Madison, WI , USA

3. Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, WI , USA

4. Department of Obstetrics & Gynecology, University of Wisconsin-Madison , Madison, WI , USA

5. Department of Pathology, Oregon Health & Science University , Portland, OR , USA

6. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison , Madison, WI , USA

7. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison , Madison, WI , USA

8. Department of Computer Science, University of Wisconsin-Madison , Madison, WI , USA

9. Department of Biomedical Engineering, University of Wisconsin-Madison , Madison, WI , USA

10. Department of Radiology, University of Wisconsin-Madison , Madison, WI , USA

Abstract

Abstract Identification of placental dysfunction in early pregnancy with noninvasive imaging could be a valuable tool for assessing maternal and fetal risk. Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) can be a powerful tool for interrogating placenta health. After inoculation with Zika virus or sham inoculation at gestation age (GA) 45 or 55 days, animals were imaged up to three times at GA65, GA100, and GA145. DCE MRI images were acquired at all imaging sessions using ferumoxytol, an iron nanoparticle-based contrast agent, and analyzed for placental intervillous blood flow, number of perfusion domains, and perfusion domain volume. Cesarean section was performed at GA155, and the placenta was photographed and dissected for histopathology. Photographs were used to align cotyledons with estimated perfusion domains from MRI, allowing comparison of estimated cotyledon volume to pathology. Monkeys were separated into high and low pathology groups based on the average number of pathologies present in the placenta. Perfusion domain flow, volume, and number increased through gestation, and total blood flow increased with gestation for both low pathology and high pathology groups. A statistically significant decrease in perfusion domain volume associated with pathology was detected at all gestational ages. Individual perfusion domain flow comparisons demonstrated a statistically significant decrease with pathology at GA100 and GA145, but not GA65. Since ferumoxytol is currently used to treat anemia during human pregnancy and as an off-label MRI contrast agent, future transition of this work to human pregnancy may be possible.

Funder

Endocrinology-Reproductive Physiology Training

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,General Medicine,Reproductive Medicine

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