PlaCEUS: Feasibility Study of Contrast-enhanced Ultrasound to Visualize Maternal Uterine Spiral Arteries Postpartum. (PlaCEUS)

During pregnancy, unique blood vessels form within the uterine wall, known as spiral arteries. These vessels originate from the uterine artery, which is the main artery supplying blood to the uterus. Throughout pregnancy, spiral arteries undergo significant changes to increase blood and oxygen flow to the placenta, ensuring the developing baby receives adequate nutrients. When these arteries fail to remodel properly, complications such as pre-eclampsia or fetal growth restriction can occur.

Until now, direct observation and evaluation of spiral arteries during pregnancy has not been feasible. Contrast-enhanced ultrasound may provide a breakthrough in this area. In this study, the investigators aim to use this imaging technique to visualize spiral arteries after the placenta has been delivered. If successful, this could allow to assess their structural quality. Additionally, the investigators will employ ultrasound to monitor physiological changes in the uterine artery during late pregnancy (after 37 weeks), during labour, and postpartum.

By conducting these measurements, the investigators hope to develop methods for detecting spiral artery abnormalities earlier in pregnancy. Early identification could enable timely interventions and help prevent severe complications.

Study Overview

• Status: Recruiting
• Conditions: Doppler Parameters; Contrast Enhanced Ultrasound; Spiral Arteries; Uterine Artery Hemodynamics; Resistance Index; Pulsatility Index; Systolic/Diastolic Ratio
• Intervention / Treatment: Diagnostic test: SonoVue (sulphur hexafluoride microbubbles)

Detailed Description

Adequate blood flow to the placenta is critical for normal fetal development and positive pregnancy outcomes. A key component of this process is the maternal uterine spiral arteries, which undergo significant physiological remodeling during pregnancy to meet the growing demands of the fetus. When this remodeling is impaired, it has been linked to complications such as preeclampsia, fetal growth restriction, and placental abruption.

Despite its importance, directly and non-invasively assessing the maternal uterine microvasculature-particularly spiral arteries-remains difficult. Conventional Doppler ultrasound only provides indirect insights by estimating vascular resistance at a macroscopic level and cannot visualize spiral arteries or directly evaluate placental perfusion. Contrast-enhanced ultrasound (CEUS) represents a promising alternative, as it improves visualization of small vessels through the use of ultrasound contrast agents (UCAs). Since UCAs are currently not approved for use during pregnancy, this study focuses on assessing the feasibility of CEUS for visualizing persistent spiral arteries in the immediate postpartum period, as an initial step toward investigating the maternal side of the placenta. In addition, Doppler waveform analysis of the uterine arteries will be performed at three time points: before delivery, during labor, and after birth. Combining CEUS with Doppler imaging may provide a more comprehensive understanding of dynamic uteroplacental vascular changes around delivery.

The primary objectives are to determine whether maternal uterine spiral arteries remain present after delivery and to evaluate the feasibility of CEUS with UCAs in visualizing and characterizing these arteries within four hours postpartum.

Secondary objectives include assessing uterine artery Doppler parameters before, during, and after delivery to describe peripartum hemodynamic changes, and correlating CEUS findings at four hours postpartum with Doppler measurements.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eveline Dekker, Drs; Phone Number: +3140 888 83 80; Email: e.dekker@mmc.nl
• Study Contact Backup: Name: Loes Monen, Dr.; Phone Number: +3140 888 83 80

Study Locations

• Netherlands
  • Veldhoven, Netherlands, 5504DB
    • Recruiting
    • Maxima Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant patient at a minimum age of 18 years
• Singleton pregnancy at term (≥37 weeks gestation)
• Planning to deliver at the Máxima Medical Centre
• Able to provide informed consent
• Intravenous access present at the time of delivery

Exclusion Criteria:

• Multiple gestation pregnancy
• Contra-indications to CEUS, e.g. known allergy for constituents of SonoVue™
• Planning on breastfeeding
• Medical emergency during or after delivery, which makes CEUS impossible or undesirable
• No intravenous access present at the time of delivery
• Body Mass Index >40 kg/m2.
• Pre-eclampsia requiring medication
• Foetal growth restriction < p3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEUS; All participants included in the study will receive contrast enhanced ultrasound imaging postpartum. During pregnancy, during labour and postpartum Doppler parameters of the uterine arterie will be performed.	Diagnostic test: SonoVue (sulphur hexafluoride microbubbles); SonoVue will be used in this study as ultrasound contrast agents for contrast enhanced ultrasound to assess the feasibility in visualizing and charactering the persistence of maternal uterine spiral arteries within 4 hours postpartum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with persisting spiral arteries detected by contrast enhanced ultrasound within 4 hours postpartum.	Presence of persisting spiral arteries will be assessed using contrast enhanced ultrasound (CEUS) with Sonovue within 4 hours postpartum. The transition of spiral arteries into the intervillous space will be identified at the interface between the decidua and the basal plate of the placenta. Depending on placental location, a sagittal or coronal plane will be selected for optimal visualization. The probe will be positioned perpendicular (90°) to the uteroplacental interface, and color Doppler will be activated to confirm unidirectional flow at the spiral artery opening. Persistence of spiral arteries will be determined as a dichotomous outcome. Visbile or not visible. The number of patients will be calculated in whom the result was: visible.	Within 4 hours postpartum
Feasibility of Contrast Enhanced Ultrasound (CEUS) with Sonovue for visualizing spiral arteries within 4 hours postpartum. Dichotomous outcome; visible or invisible spiral arteries.	Feasibility will be assessed by determining whether CEUS with Sonovue successfully visualizes and characterizes maternal uterine spiral arteries within 4 hours postpartum. A scan will be considered feasible if the transition of spiral arteries into the intervillous space can be identified at the uteroplacental interface using the predefined imaging protocol (correct probe orientation, sagittal/coronal plane selection, and confirmation of unidirectional flow with color Doppler). The outcome is dichotomous. The spiral arteries are visible or not visible.	Within 4 hours postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in uterine artery Resistance Index (RI) across peripartum period	Uterine artery resistance index (RI) will be measured using Doppler ultrasound before delivery (after 37 weeks) Uterine artery resistance index (RI) will be measured using Doppler ultrasound during delivery (active labor or same day prior to cesarean) Uterine artery resistance index (RI) will be measured using Doppler ultrasound within 4 hours postpartum.	Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.
Change in uterine artery Pulsatility Index (PI) across peripartum period	Uterine artery pulsatility index (PI) will be measured using Doppler ultrasound before delivery (after 37 weeks), Uterine artery pulsatility index (PI) will be measured using Doppler ultrasound during delivery (active labor or same day prior to cesarean) Uterine artery pulsatility index (PI) will be measured using Doppler ultrasound within 4 hours postpartum. The change in PI will be assesed as delta PI, both absolute as in percentage change of PI.	Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.
Change in uterine artery Systolic/Diastolic Ratio across peripartum period	Uterine artery systolic/diastolic ratio will be measured using Doppler ultrasound at three time points: before delivery (after 37 weeks), during delivery (active labor or same day prior to cesarean), and within 4 hours postpartum.	Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.
Correlating CEUS findings with uterine artery Doppler parameters within 4 hours postpartum	Correlation will be assessed between CEUS findings (presence of persisting spiral arteries detected using contrast enhanced ultrasound with Sonovue) and uterine artery Doppler parameters (Resistance Index [RI], Pulsatility Index [PI], and Systolic/Diastolic ratio). CEUS will follow the standardized imaging protocol for spiral artery visualization, and Doppler measurements will be obtained using standard obstetric ultrasound techniques.	Within 4 hours postpartum

Collaborators and Investigators

• Sponsor: Maxima Medical Center

Publications and helpful links

General Publications

• Collins SL, Birks JS, Stevenson GN, Papageorghiou AT, Noble JA, Impey L. Measurement of spiral artery jets: general principles and differences observed in small-for-gestational-age pregnancies. Ultrasound Obstet Gynecol. 2012;40(2):171-178. doi:10.1002/uog.10149.
• Roberts VHJ, Morgan TK, Bednarek P, et al. Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology. Hum Reprod. 2017;32(12):2382-2393. doi:10.1093/humrep/dex301
• Li QY, Li Y, Li X, Liu Y, Zhang Y, Zhang Y, et al. Safety analysis of adverse events of ultrasound contrast agent Lumason/SonoVue in 49,100 patients. Front Cardiovasc Med. 2022;9:1003452. doi:10.3389/fcvm.2022.1003452.
• Claudon M, Cosgrove D, Albrecht T, Bolondi L, Bosio M, Calliada F, et al. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) - Update 2008. Ultraschall Med. 2008;29(1):28-44. doi: 10.1055/s-2007-963785
• Dassen S, Monen L, Oei G, Mischi M, van Laar J. Safety of contrast-enhanced ultrasound using microbubbles in human pregnancy: A scoping review. Ultraschall Med. 2025 Jun;46(3):259-269. doi: 10.1055/a-2351-0747. Epub 2024 Jun 24.
• European Medicines Agency (EMA). SonoVue, INN-sulphur hexafluoride: EPAR - Product Information. EMA. Last updated: 05 June 2023. Available from: https://www.ema.europa.eu/en/documents/product-information/sonovue-epar-product-information_en.pdf

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 17, 2025
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Spiral arteries; Uterine artery hemodynamics; contrast enchanced ultrasound
• Additional Relevant MeSH Terms: Heart Murmurs; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Systolic Murmurs
• Other Study ID Numbers: NL010727

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All participant will sign informed consent stating that all data will be used anonymously.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No