PhD Position - Vascular Imaging of the Uterus

Advisors:

Name: Justine Robin & Béatrice Walker

E-mail: justine.robin@espci.fr, beatrice.walker@inserm.fr

The objective of this PhD project is the characterization of the uterus vasculature in the non-pregnant state. Using ultrafast ultrasound, the student will image this vasculature at different time points of the hormonal cycle to study morphological and functional changes under physiological conditions.

Scientific Context: need for a better understanding of the uterus vasculature

The uterine vasculature is unique in its remarkable ability to undergo dynamic and cyclical remodeling throughout a woman’s reproductive life. The uterine vessels experience physiological angiogenesis during each menstrual cycle, with blood vessels continuously growing and regressing. Spiral arteries, in particular, are small arteries that temporarily supply blood to the endometrium – the inner lining of the uterine cavity – during the second phase of the menstrual cycle, also called the luteal. Studies on the endometrial spiral arteries of the human non-pregnant uterus indicated the remarkable sensitivity of these vessels to stimuli by hormones or growth factors, while the basal arteries are thought to be more stable, non-hormone-responsive structures. The convoluted course of the spiral arteries results from arterial growth exceeding the increase in endometrial thickness during the cycle, and this spiral shape has dramatic hemodynamic repercussions.

During pregnancy, these spiral arteries play a crucial role in supplying nutrients to the placenta and fetus. To fulfill this function, they undergo extensive remodeling, transforming into highly dilated vessels under the influence of invading trophoblast cells—the outer layer of the blastocyst that will develop into the placenta. This requires global remodeling of both small and large vessels, including a significant reduction in vascular resistance to facilitate adequate utero-placental exchange. This extraordinary adaptability highlights the crucial role of vascular remodeling in gynecology, reproductive health, and pregnancy outcomes.

Despite its tremendous clinical interest, the uterus vasculature today remains poorly understood, as its comprehensive assessment often requires invasive or post-mortem procedures ¹. Ultrasound examination is the first-line, non-invasive, diagnostic tool for gynaecologists, and can provide real-time visualization of uterine tissue anatomy in B-Mode and blood flow information in large vessels through Doppler modes ^2–4. The main part of the vasculature, however, remains completely invisible, especially the very small vessels irrigating the endometrium.

Growing evidence suggests a strong link between uterine receptivity and vascular status, highlighting the potential impact of a detailed vascular assessment for assisted reproductive technologies (ART). ART has revolutionized fertility treatment, now contributing to 2–4% of births across Europe. However, success rates remain low, with only about one-third of embryo transfers resulting in live birth, leaving many women struggling to conceive. A deeper understanding of these small vessels would also be invaluable in improving the early diagnosis and management of pregnancy complications such as pre-eclampsia and fetal growth restriction. Studies have indeed shown that inadequate spiral artery remodeling plays a key role in these disorders. However, while the most dynamic changes in uterine circulation occur before mid-gestation, no existing imaging technique allows direct visualization of this remodeling process in early pregnancy.

This PhD project builds on the hypothesis that recent advances in ultrafast ultrasound imaging —a ground-breaking imaging technology capable of capturing thousands of images per second with high sensitivity — may address this limitation.

Project Outline:

In the first phase of the project, the student will develop the missing technologies to adapt ultrafast ultrasound imaging to explore the uterus micro-vasculature, and characterise its hemodynamics.  Specifically, he/she will:

1. Develop ultrasound sequences, image reconstruction, and image processing tools specifically adapted to transvaginal ultrasound imaging (TVUS), accounting for its unique probe geometry (a small aperture and strong curvature) and clinical constraints
2. Build an ex vivo setup to imagethe  explanted uterus under perfusion in well-controlled conditions
3. Characterize the performance of our method in these well-controlled conditions

In the second phase, these technological developments will be used to study the uterus vasculature at different phases of the hormonal cycle. Two novel ultrafast ultrasound imaging modalities will be used: ultrafast Doppler, which provides blood flow imaging with a resolution of ~100µm, and Ultrasound Localisation Microscopy (ULM, a cutting-edge technique that uses micro-bubbles as contrast agents. Once injected into the vasculature, they are localized and tracked through ultrasound imaging, enabling the creation of high-resolution maps of hemodynamic properties. We will implement these 2 imaging modalities in an ex vivo preclinical model (sheep). The goal will be to:

1. Reconstruct a high-quality map of the microvasculature at four different stages of the oestrous cycle
2. Develop a data analysis pipeline to characterize the myometrial and endometrial vessels (densities, vessel diameters, tortuosity…)
3. Study the dynamics of these markers over the oestrous cycle.

Finally, building on these results, the PhD student will participate in a clinical proof-of-concept study to provide the first characterization of temporal and spatial uterine vascular dynamics throughout a physiological menstrual cycle. We will then test our method in pathological conditions: a group of non-pregnant recurring pre-eclampsia patients with chronic hypertension will be imaged and compared to healthy controls to characterize disease phenotypes.

Candidate profile:

We are looking for a student interested in the interface between physics and medicine, proficient in coding and physics (acoustics), preferably with some experience in benchtop experiments.