Development of a new 3D virtual desktop imaging technique for real time non-invasive evaluation of the utero-placental interface vascularization throughout pregnancy.

Early placental development plays a critical role in human reproduction.
Development of the placental vascular bed is not only related to adverse
pregnancy outcomes, but has also been shown to be associated with maternal and
child health during the life course. Impaired placental development is thought
to contribute to the occurrence of non-communicable diseases. Several
periconception maternal environmental influences, in particular lifestyle like
nutrition and smoking, interact with placental development and functioning, but
are also related to preconceptional (sub)endometrial and uterine
vascularization.

Hence, knowledge on placental development needs to be expanded in the second
and third trimester of pregnancy, but also during the first trimester of
pregnancy. Therefore, there is a need for a patient-friendly, rapid,
non-invasive and safe evaluation technology that can be applied throughout
pregnancy, cross-linking clinical information, including maternal environmental
influences, and placental development and functioning with novel morphological
and quantitative data on the placental bed vasculature.

The rationale for the evaluation of maternal lifestyle in relation to fetal
development is based on epidemiological and animal studies. However, maternal
lifestyle also has an impact on placental vascularization and development, but
it is not known how lifestyle operates or whether lifestyle affects the
vasculature of the nonpregnant uterus. Therefore, we will study associations
between maternal lifestyle and uterine and placental indices obtained by the
non-invasive technology (i.e. VIRTUAL clinical prototype). If in future
patients with poor lifestyle can be identified, lifestyle, modification of
these behaviours could create a healthy placental environment thereby
optimizing health for mother and unborn child.

Part I Preclinical study using the VIRTUAL preclinical prototype
Primary objective:
- To validate the reliability and applicability of regular use of the VIRTUAL
(pre)clinical prototype in a bed-side setting (desktop) preconceptional and
across pregnancy. During the first trimester preferably, only placental
structures will be scanned using power Doppler and as such the embryo lies
outside the Doppler ultrasound beam.

Part II Clinical study using the VIRTUAL clinical prototype
Primary objective:
- To investigate the development of the uterine- and utero-placental
circulation and intra-placental vascularization of the preconception
nonpregnant uterus and the placenta across pregnancy.

Part I Preclinical study using the VIRTUAL preclinical prototype:
A pilot observational cohort study will be performed in (non)-pregnant women to
investigate 3D power Doppler scans obtained of the preconception uterine
vascular bed and placenta during pregnancy using the VIRTUAL preclinical
prototype.

Part II Clinical study using the VIRTUAL clinical prototype:
An observational cohort study will be performed in nonpregnant (PREC cohort)
and pregnant women (PREG cohort). To investigate 3D scans using the VIRTUAL
clinical prototype.

For all participants the risks involve primarily the burden of participating in
a study, which usually means additional hospital visits and assessments. The
risks of participation are considered to be minor and the potential benefit
outweighs the risks. From the above, it is clear that there are no obvious
risks associated with participation in the study.

The availability of a safe, near real-time, non-invasive, rapid, easy-to-use
and cheap method of relating maternal conditions and lifestyle and clinical
outcomes to uterine and placental bed vascularization, will have a high impact
on current clinical practice. The development of VIRTUAL may lead to the use of
maternal biomarkers to assess uterine and placental function, the amelioration
of clinic decision-making based on imaging alone versus imaging in combination
with assessment of biomarkers and might provide future intervention strategies
eventually leading to life-long reduced risk of non-communicable diseases.
Therefore, this project will have an impact on research, clinical care
individual and public health as well as on future medical health care costs.