Elucidating the contribution of microvascular remodeling to cervical softening during pregnancy with quantitative ultrasound - PROJECT SUMMARY Despite efforts to improve medical practices, the rate of preterm birth in the United States continues to climb; more than 1 in every 10 babies are born too soon. Many do not survive and those that do are susceptible to lifelong health problems. Our inability to predict the time of delivery reflects our poor understanding of the complex physiology of pregnancy and birth in general; while it is clear that the cervix softens, shortens and dilates in preparation for birth, that microstructural changes underlie this process, and that premature changes precede preterm delivery, precise information about how and why this remodeling occurs is lacking. As such, non-invasive, in vivo methods are desperately needed to identify cervical remodeling in pregnant patients. Cervical softening is a critical parameter to the clinician because it markedly accelerates near delivery (term or preterm). Vascular changes are clearly fundamental to the remodeling of many tissues, but have never been comprehensively explored in the cervix, in part because of technical limitations (resolution and sensitivity) of previous imaging attempts. In this proposal, we leverage our expertise in statistical image reconstruction and deep learning to develop a novel microvascular ultrasound imaging method with the potential to dramatically improve the resolution and sensitivity by jointly minimizing errors in image reconstruction and the blurring effects associated to the ultrasound beam size. We use this reconstruction approach, named Statistical icrovascular Doppler, or S-Doppler, to shine light on the microvascular changes of the cervix during pregnancy. Briefly, in aim 1 we optimize S-Doppler in calibrated phantoms to maximize resolution and contrast in microvessel imaging. In aim 2, we validate in vivo the performance of the optimized technique to detect microvascular remodeling in the gravid Sprague-Dawley rat, in which in vivo and ex vivo validation with Super- Resolution Ultrasound (using microbubbles) and micro-Computed Tomography, respectively, are feasible. In aim 3, we demonstrate the translational potential of S-Doppler through a longitudinal study in pregnant Rhesus macaques and investigate the contribution of microvasculature changes to cervical softening using an assay of quantitative imaging biomarkers implemented on the same ultrasound probe. The outcome of this proposal will be a novel, high resolution reconstruction approach to ultrasound microvascular imaging without the need of microbubble-based contrast agents. Quantitative features extracted from it will add to a growing toolkit of non-invasive in vivo imaging biomarkers for defining a personalized ultrasound “fingerprint” of cervical remodeling, either at term or preterm. Ultimately, such tools will facilitate a comprehensive understanding of specific cervical microstructural changes in a particular person’s pregnancy, leading to accurate screening and tailored interventions that will help reduce the number of preterm births. 1
