Assessment of uterine cervical insufficiency using 4D contrast-enhanced ultrasound - cervical insufficiency (CI) describes the inability of the uterine cervix to retain a pregnancy in the absence of…

This $429,000 Project Grant award from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865) aims to determine if blood perfusion and microvascular pressure around the internal os of the uterine cervix can distinguish patients with a history of cervical insufficiency (CI) from normal controls in a non-pregnant state. The researchers at Thomas Jefferson University will use contrast-enhanced ultrasound to assess cervical blood flow and pressure as potential markers of cervical weakness. The award runs from September 2024 through August 2026 and supports this novel research approach to better understand the pathophysiology of CI, which can lead to mid-trimester pregnancy loss. The findings could help develop an objective diagnostic test for CI outside of pregnancy.

Assessment of uterine cervical insufficiency using 4D contrast-enhanced ultrasound - cervical insufficiency (CI) describes the inability of the uterine cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, or labor, or both in the second trimester. The presumed cause of CI is "weak" cervical tissue, intrinsic or acquired. However, the known pathophysiology of CI is extremely limited. The current CI diagnosis is based on either a past obstetric history or on a combination of obstetric history and transvaginal ultrasound measurement of cervical length. Nonetheless, there is no objective test to evaluate cervical tissue strength as a means to confirm a diagnosis of CI. Moreover, the diagnosis of CI cannot be made outside of pregnancy by any test. Recently, cervical function has been considered to be a continuum instead of a dichotomy. Previous studies showed that the collagen content in biopsy specimens was lower in patients with CI and in non-pregnant women complicated by previous mid-trimester abortions compared to controls. These findings suggest that the assessment of cervical function before pregnancy may identify a "weak" cervix with a baseline functional defect, which varies with the severity of weakness. While the mechanical strength of the cervix is known to partly rely on the collagen network in the extracellular matrix, recent studies found that the internal OS area is significantly more cellular than the external OS and contains around 50-60% smooth muscle cells (smcs). The smcs of the internal OS are generally circumferentially oriented around the endocervical canal, possibly similar to a "sphincter", whose functional failure may explain why the internal OS dilates/funnels first in premature cervical remodeling. In case of normal "multiparous cervix", the external OS remains soft and dilated, while the internal OS is firmly closed. Hence, IT may be necessary to assess the "sphincter" function of the cervix to assess its "weakness". In studies on various smooth muscle organs, the smooth muscle function is related to the local blood flow and perfusion. Thus, in this study, we suggest using contrast-enhanced ultrasound (ceus) to quantify the blood perfusion in the cervix. Ceus uses the administration of an intravenous ultrasound contrast agent (UCA) comprised of gas-filled microbubbles that remain within blood vessels reflecting vascularization and blood perfusion. Furthermore, we suggest the novel concept evaluating the microvascular pressure (MVP) of the cervix as a functional marker to assess the cervical weakness. MVP is a driving force for local blood perfusion. UCA not only enhances the backscattered ultrasound signals, but can also act as pressure sensors. Our group developed the fundamental concept of subharmonic (half of fundamental frequency) aided pressure estimation (shape) using ceus and showed its potential to noninvasively estimate intra-cardiac pressures, hepatic venous pressure gradients, and tumoral interstitial fluid pressure in patients. The objective of this study is to determine if the blood perfusion and/or MVP around the internal OS of uterine cervix can distinguish patients with a history of CI (presumably "weak" cervix) from normal controls in a non-pregnant state. We hypothesize that the blood perfusion is higher with lower MVP around the internal OS in patients with a history of CI than in normal controls.