This project, led by Dr. Ivan Rosado Mendez, aimed to develop and implement ultrasound microvessel imaging (UMI) as a functional imaging technique to study cervical remodeling during pregnancy in real time. Cervical remodeling describes the progressive changes of the cervix during pregnancy and involves four phases: softening, ripening, dilation and postpartum repair. If the cervix ripens in preparation for delivery too early, it can cause premature birth. Preterm birth (PTB), defined as delivery before 37 weeks of pregnancy, results in one million deaths worldwide and is associated with significant racial and socioeconomic disparities.
The researchers successfully developed a cervical tissue-mimicking model, called a phantom, composed of agar-based simulated tissue, fluid-carrying channels, blood-mimicking fluid and a system to control fluid dynamics. They validated channel dimensions with micro-CT scans, ensured stability over 14 days and selected a fluid that best matched the features of human blood for the prototype. Finally, the team implemented a high-resolution imaging protocol that was able to detect fluid movement through the channels even when surrounded by simulated tissue.
The Challenge
Preterm birth (PTB), defined as delivery before 37 weeks of pregnancy, affects approximately 15 million babies and results in one million deaths worldwide each year. Wisconsin’s PTB rate is 10.1 percent, matching the national average. This rate has been continually rising since 2013, with significant disparities among different racial and socioeconomic groups. There is a pressing need for innovative approaches to understand and prevent PTB, and researchers believe that the functional imaging approaches used in cancer treatment could be used in the obstetric setting to understand cervical remodeling during pregnancy. Cervical remodeling describes the progressive changes of the cervix during pregnancy and involves four phases: softening, ripening, dilation and postpartum repair. If the cervix ripens in preparation for delivery too early, it can cause premature birth; however, previous attempts to use 3D ultrasound to monitor cervical changes were inconclusive due to resolution limitations.
Project Goals
The goal of this project was to develop and implement ultrasound microvessel imaging (UMI) as a functional imaging technique to study cervical changes during pregnancy in real time. By combining ultrafast imaging techniques and advanced signal processing, UMI aimed to achieve higher resolution than conventional, 3D ultrasound methods. This goal was addressed through two specific aims:
Design, fabricate and characterize a phantom model that mimics cervical tissue to validate the application of UMI.
Demonstrate that UMI can accurately capture detailed images of blood flow and tissue structure in the cervix.
Results
The researchers successfully developed a tissue-mimicking phantom that has several components, including agar-based material to simulate tissue, wall-less channels for fluid flow, blood-mimicking fluid that is perfused through the channels and a microfluidics system that is used to control the pressure and flow rate of the blood-mimicking fluid as it travels through the channels. The channel dimensions were validated using micro-CT scans, corrected for spatial resolution and confirmed for stability over 14 days. Researchers characterized the acoustic properties of the blood mimicking fluid and chose the formulation that most closely matched human blood for use in the final phantom prototype. Finally, they constructed the final phantom for use in their imaging studies.
Despite some technical challenges, the team successfully implemented a high-resolution imaging sequence on the Verasonics Vantage 256 scanner. The imaging effectively detected movement within the vessels, even when surrounded by the tissue-mimicking materials. In future work, the imaging techniques will be tested with ultrasound contrast agents using the final phantom version. Ultimately, the phantom designed in this project could be used to standardize performance validations across ultrasound scanners in the commercial setting.
