Background: This study is a proof-of-concept, case-control exploration of quantitative
ultrasound (QUS) and ultrafast power Doppler imaging (uPDI) imaging techniques, applied
to the placenta to evaluate health of the placenta, blood flow visualized by colored
doppler imaging in patients with and without FGR. Investigators will utilize the
Verasonics Vantage 256 research ultrasound machine (Verasonics, Inc, Kirkland, WA) for
this study, which is not FDA approved/experimental, along with a standard-of-care
Phillips ultrasound machine which is FDA approved.
Use of QUS gained interest within the 1980s to evaluate the health of a range of tissues,
from myocardial [heart muscle], to artery plaques, to breast masses, to bone density.
More recently, there has been great interest in QUS for evaluation of fetal tissue
health, including fetal liver and lung tissue, as well as placental tissue to gauge both
gestational age as well as placental health. QUS imaging creates a number of values
including an attenuation coefficient estimate (ACE), specified in decibels (dB) which is
a measurement of the ultrasound waves' absorption and scattering as they move through
human tissue. QUS also generates other values including a frequency-dependent attenuation
value. These numerical estimates of absorption and scattering along with others provided
by QUS are believed to change within the placenta with increased gestational age due to
increasing deposition of collagen and fibrin, two types of connective fibers. Measures of
absorption, scattering, and related tissue properties may also be altered in unhealthy
versus healthy placental tissue. Thus, QUS is believed to have the potential to inform
the clinician about placental health which may be affected by uteroplacental
insufficiency predisposing to fetal growth restriction. Researchers will also investigate
power Doppler imaging (uPDI), a newer ultrasound modality that uses an ultra-high frame
rate and clutter filtering to increase the Doppler imaging sensitivity. Traditional
Doppler ultrasound displays color onto the normally greyscale ultrasound where blood flow
is seen by the machine. However, traditional ultrasound with Doppler has difficulty in
detecting blood flow within smaller vessels, such as the smallest spiral arteries of the
placenta which provide nutrient and gas exchange to the fetus. It is believed uPDI may be
able to better visualize these small vessels and other small areas of slow blood flow or
pooled blood within the placenta, providing more direct evaluation of placental tissue
perfusion and health.
Procedure: Ultrasounds will be performed every 3 weeks until delivery for both cohorts
following informed consent. The first ultrasound will take place within 1 week of
enrollment to allow for the sonographer to be scheduled. Ultrasounds will be performed by
trained MFM sonographers. Ultrasounds will take place within the Maternal Fetal Medicine
suite of Carilion Clinic [102 Highland Ave, Roanoke, VA], in clinical exam rooms with
dimmable lights and calming music to reduce patient stress. Upon entering the exam room,
IRB-approved study team members and/or sonographers will introduce themselves by name and
capacity, then ask the name and date of birth of the subject to verify subject identity
against the research enrollment log and EMR. The purpose for the visit will be reiterated
and the subject's wish to continue to participate in the research will be verified to
ensure continued consent. Any questions the subject has will be answered to the subject's
satisfaction. An agenda for the encounter will be set by the IRB-approved study team
member or sonographer, so the patient knows what to generally expect and how long the
visit will take. The subject will be seated in a reclined position and asked to raise the
bottom portion of their shirt, while the sonographer drapes the patient according to
standard clinical procedure. Ultrasound gel will be applied to the subject's abdomen and
the sonographer will then begin the ultrasound using the machine's transducer [part held
in sonographer's hand].
To begin, an ultrasound using a standard-of-care, Philips ultrasound machine will be used
to first verify continued fetal viability and perform a basic anatomical survey to ensure
continued eligibility for the subject's given cohort [either Case [FGR-positive] or
Control [FGR-negative]]. These Philips ultrasound machines are located in each of the
standard MFM exam rooms. Following this, the sonographer will transition to the research
ultrasound machine for the rest of the visit.
Participants will have research ultrasounds performed of their placentas using a
Verasonics Vantage 256 system (a popular research ultrasound platform used for human
imaging under IRB approval). The gestational age of the fetus, estimated fetal weight in
grams, and growth/weight percentile measurements for that gestational age will be
recorded during the research visits. The placenta will be scanned at a central,
peripheral, and 'mid-disc' region to acquire QUS and uPDI images with the Verasonics
research ultrasound as well. Three measurements will be acquired at these locations. The
Verasonics machine will be programmed to project B-mode (brightness mode) images for the
sonographer at the time of the research ultrasound for confirmation of correct placental
location. These B- or brightness mode images will project a 2-dimensional, greyscale
image of the placenta (or fetus) to the sonographer to orient him/her to the location
they are scanning and find the placenta. The machine will be programmed to display
thermal index (TI) and mechanical index (MI) during all exams, which are derived
estimates of the heat and pressure created by ultrasound waves' energy. These are
displayed for safety and kept within International Society of Ultrasound of Obstetrics
and Gynecology (ISUOG) guidelines. The Verasonics machine will be programmed with a "hard
stop" not to exceed these limits. The energy exposure from Ultrasound has no known
cumulative effect. Following the ultrasound procedure, the subject will be cleaned of
ultrasound gel with a cloth and drapes removed. The subjects will be told of any changes
noticed since the last visit to the growth or health of their baby or placenta.
Incidental findings obtained during the research ultrasound will be shared with the
subject's routine clinical provider and the patient by IRB-approved and qualified
physicians on the research team. The PI will advise the participant's routine clinical
provider that all results obtained with the research ultrasound should be validated using
an FDA Approved ultrasound and standard of care ultrasound techniques.
Following all research ultrasound procedures during the visit, subjects will be given an
opportunity to ask any further questions they wish and receive answers to their
satisfaction. Printouts of their baby from the standard-of-care ultrasound machine will
be provided to subjects. Subjects will then be led back out of the MFM suite to the front
desk where they will be scheduled for their next research visit.
Participants will not be under the primary care of the research physicians. The research
physicians will not be involved in decisions regarding the timing, method, or procedures
used to terminate a pregnancy or determining the viability of a neonate.
Analysis: Researchers will evaluate QUS and uPDI images of the placentas. Researchers
will evaluate which QUS parameters are most strongly associated with FGR diagnosis by
comparing them to numbers obtained by QUS in normal estimated fetal growth pregnancies.
Researchers will examine uPDI images in FGR pregnancies versus those obtained from normal
growth weight pregnancies.
Secondary analysis: Researchers will perform multimodal analysis to determine whether
these ultrasound modalities can distinguish between pregnancies with: A.) confirmed
diseases deriving from a placental origin; B.) abnormal umbilical artery assessments,
severe FGR, preeclampsia and stillbirth; C.) no complications.
