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

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.

SUBMITTER: Seiter DP

PROVIDER: S-EPMC9752971 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Seiter Daniel P DP Nguyen Sydney M SM Morgan Terry K TK Mao Lu L Dudley Dawn M DM O'connor David H DH Murphy Megan E ME Ludwig Kai D KD Chen Ruiming R Dhyani Archana A Zhu Ante A Schotzko Michele L ML Brunner Kevin G KG Shah Dinesh M DM Johnson Kevin M KM Golos Thaddeus G TG Wieben Oliver O

Biology of reproduction 20221201 6

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, a ...[more]

PMID: 36018823

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Project description:BACKGROUND:The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. OBJECTIVE:We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. STUDY DESIGN:Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. RESULTS:In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies. CONCLUSIONS:Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.

Project description:BackgroundBright-blood and black-blood cardiovascular magnetic resonance (CMR) techniques are frequently employed together during a clinical exam because of their complementary features. While valuable, existing black-blood CMR approaches are flow dependent and prone to failure. We aim to assess the effectiveness and reliability of ferumoxytol enhanced (FE) Half-Fourier Single-shot Turbo Spin-echo (HASTE) imaging without magnetization preparation pulses to yield uniform intra-luminal blood signal suppression by comparing FE-HASTE with pre-ferumoxytol HASTE imaging.MethodsThis study was IRB-approved and HIPAA compliant. Consecutive patients who were referred for FE-CMR between June 2013 and February 2017 were enrolled. Qualitative image scores reflecting the degree and reliability of blood signal suppression were based on a 3-point Likert scale, with 3 reflecting perfect suppression. For quantitative evaluation, homogeneity indices (defined as standard deviation of the left atrial signal intensity) and signal-to-noise ratios (SNR) for vascular lumens and cardiac chambers were measured.ResultsOf the 340 unique patients who underwent FE-CMR, HASTE was performed in 257. Ninety-three patients had both pre-ferumoxytol HASTE and FE-HASTE, and were included in this analysis. Qualitative image scores reflecting the degree and reliability of blood signal suppression were significantly higher for FE-HASTE images (2.9 [IQR 2.8-3.0] vs 1.8 [IQR 1.6-2.1], p < 0.001). Inter-reader agreement was moderate (k = 0.50, 95% CI 0.45-0.55). Blood signal suppression was more complete on FE-HASTE images than on pre-ferumoxytol HASTE, as indicated by lower mean homogeneity indices (24.5 [IQR 18.0-32.8] vs 108.0 [IQR 65.0-170.4], p < 0.001) and lower blood pool SNR for all regions (5.6 [IQR 3.2-10.0] vs 21.5 [IQR 12.5-39.4], p < 0.001).ConclusionFE-HASTE black-blood imaging offers an effective, reliable, and simple approach for flow independent blood signal suppression. The technique holds promise as a fast and routine complement to bright-blood cardiovascular imaging with ferumoxytol.

Dataset Information

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

Publications

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

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