Ferumoxytol-enhanced magnetic resonance imaging with volume rendering: A new approach for the depiction of internal placental structure in vivo

Kliewer, Mark A.; Bockoven, Crystal; Reeder, Scott B.; Bagley, Anjuli R; Fritsch, Michael K.

doi:10.1016/j.placenta.2022.12.001

Cited by 7 publications

(2 citation statements)

References 18 publications

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“…The transverse diameter of the terminal villi and the transverse diameter of the terminal villous capillaries were considerably smaller in group B pre-eclamptic placentae than in group A control placentae in the current study. As per documented data, the majority of the morphological alterations in the placenta in pre-eclampsia may be caused by decreased uteroplacental blood flow, which also accounts for the patho-physiological changes in internal components of the placenta (18,19). Studies have reported that the transverse diameter of terminal villi and terminal villous capillaries were significantly smaller in the pre-elamptic group than in the control group which is in parallel to current research (20,21).…”

Section: Discussionsupporting

confidence: 76%

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Khilji,

Rizvi,

Tarique

et al. 2023

PJMHS

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Background: The placenta reflects the prenatal problems that are linked to high perinatal morbidity and mortality both macroscopically and microscopically. A pregnancy syndrome called pre-eclampsia has terrible consequences for both the mother and the unborn child. It may result in more frequent inductions of labor, fetal growth limitation, respiratory issues in newborns, increased admission rates to neonatal critical care units, and an elevated risk of perinatal or fetal death. To understand the relation of preeclampsia and fetal growth identification of its effects on various components of the placenta is mandatory hence the current study was designed to evaluate the Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-eclamptic Pregnancies. Methodology: It was a cross sectional study, carried out on 50 samples of placentas, out of which 25 were preeclamptic and 25 were normal. The placentas were recruited after cesarean session, processed as per guidelines and were analyzed for histopathological examination. The set inclusion criteria were Registered cases of Pre-eclampsia, Blood Pressure ≥ 140/90 mmHg, Parity 0 – 4, Age of mother (25 – 35) Years., Gestational Age (36 – 42) Weeks, Mode of delivery Cesarean Sections. The set exclusion criteria were known hypertensive patients, and patient diagnosed with other chronic illnesses. Results: Number of terminal villi, Transverse diameter of terminal villi (μm), Intervillous space (μm), and Transverse diameter of terminal villous capillaries decreased significantly (p=0.001) in preeclamptic group however, Number of terminal villous Capillaries were found to be increased in preeclamptic group (p=0.001). Conclusion: Preeclampsia leads to more significant alterations in placental structure compared to normal pregnancies, emphasizing the importance of early detection and management of this condition to improve maternal and fetal outcomes. Keywords: Pregnancy, preeclampsia, terminal villi, Intervillous space, terminal villous Capillaries

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Section: Discussionsupporting

confidence: 76%

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Khilji,

Rizvi,

Tarique

et al. 2023

PJMHS

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“…Ferumoxytol has been used off-label as a contrast agent for vascular imaging, perfusion imaging, and other applications [17]. Multiple sites have begun studies to determine the efficacy of this technique for diagnosing PAS and other placental disorders [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Feasibility Study of Ferumoxtyol for Contrast-enhanced MRI of Retroplacental Clear Space Disruption in Placenta Accreta Spectrum (PAS)

Badachhape

Burnett

Bhandari

et al. 2023

Preprint

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Introduction: Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation, but visualization with conventional imaging techniques is a challenge. In this study, we investigate use of an FDA-approved iron oxide nanoparticle, ferumoxytol, for contrast-enhanced magnetic resonance imaging of the RPCS in mouse models of normal pregnancy and PAS. We then demonstrate the translational potential of this technique in human patients presenting with severe PAS (FIGO Grade 3C), moderate PAS (FIGO Grade 1), and no PAS. Methods: A T1-weighted gradient recalled echo (GRE) sequence was used to determine the optimal dose of ferumoxytol in pregnant mice. Pregnant Gab3-/- mice, which demonstrate placental invasion, were then imaged at day 16 of gestation alongside wild-type (WT) pregnant mice which do not demonstrate invasion. Signal-to-noise ratio (SNR) was computed for placenta and RPCS for all fetoplacental units (FPUs) with ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) and used for the determination of contrast-to-noise ratio (CNR). Fe-MRI was also performed in 3 pregnant subjects using standard T1 and T2 weighted sequences and a 3D magnetic resonance angiography (MRA) sequence. RPCS volume and relative signal were calculated in all three subjects. Results: Ferumoxytol administered at 5 mg/kg produced strong T1 shortening in blood and led to strong placental enhancement in Fe-MRI images. Gab3-/- mice demonstrated loss of hypointense region characteristic of the RPCS relative to WT mice in T1w Fe-MRI. CNR between RPCS and placenta was lower in FPUs of Gab3-/- mice compared to WT mice, indicating higher degrees of vascularization and interruptions throughout the space. In human patients, Fe-MRI at a dose of 5 mg/kg enabled high uteroplacental vasculature signal and quantification of the volume and signal profile in severe and moderate invasion of the placenta relative to a non-PAS case. Discussion: Ferumoxytol, an FDA-approved iron oxide nanoparticle formulation, enabled visualization of abnormal vascularization and loss of uteroplacental interface in a murine model of PAS. The potential of this non-invasive visualization technique was then further demonstrated in human subjects. Diagnosis of placental invasion using Fe-MRI may provide a sensitive method for clinical detection of PAS.

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Cotyledon‐Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast‐Enhanced MRI

Chen,

Seiter,

Keding

et al. 2024

Magnetic Resonance Imaging

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BackgroundRecently, dynamic contrast‐enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions.PurposeTo measure cotyledon‐specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury.Study TypeProspective animal model.SubjectsPlacental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 μg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165).Field Strength/Sequence3 T, T1‐weighted spoiled gradient echo sequence (product sequence, DISCO).AssessmentSource images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP‐1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals.Statistical TestsWilcoxon rank sum test, significance level P < 0.05.ResultsNo motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute−1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel‐treated (single dose) animal and both Tisseelx3 (triple dose) animals.Data ConclusionThis study demonstrates the feasibility of cotyledon‐specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol‐enhanced DCE MRI.Level of EvidenceNATechnical EfficacyStage 2

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Ferumoxytol-enhanced magnetic resonance imaging with volume rendering: A new approach for the depiction of internal placental structure in vivo

Cited by 7 publications

References 18 publications

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Feasibility Study of Ferumoxtyol for Contrast-enhanced MRI of Retroplacental Clear Space Disruption in Placenta Accreta Spectrum (PAS)

Cotyledon‐Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast‐Enhanced MRI

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