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.