Toward Non-invasive Biomarkers of Pre-term Birth: In Vivo Ultrasound Speckle Statistics in the Human Cervix Throughout Gestation.

OBJECTIVE: Researchers and clinicians have called for early pregnancy biomarkers of pre-term delivery, especially in the uterine cervix, a crucial player in delivery timing. The goal of this study was to develop practical biomarkers that can help predict the timing of delivery using ultrasound images. Here we investigated first-order speckle statistics as a lens into the remodeling microstructure of the cervix throughout gestation. METHODS: Thirty low-risk pregnant subjects were analyzed. Transvaginal ultrasound exams with a prototype linear array transducer were performed five times throughout pregnancy and once post-partum. Parameters of the Nakagami and homodyned K distributions were estimated from the envelopes of raw radiofrequency signals at a range of beam steering angles. The steering angle dependence of these parameters was also analyzed to quantify changes in microstructural anisotropy. Linear mixed effects modeling was performed for each speckle statistics metric, using subject age, parity, location of measurement within the cervix and time remaining to delivery as predictors. RESULTS: The metric most influenced by delivery timing was the steering angle dependence of the Nakagami m parameter in the posterior cervix near the internal os, where the linear mixed effects model showed an increase of 1.9±0.5% per wk in the variation of m with respect to the steering angle compared with a variation of m with respect to the steering angle at 40 wk from delivery (p<0.05). All other speckle statistics metrics and their steering angle dependence also had statistically significant relationships with delivery timing. Subject age and parity had a negative correlation with speckle statistics anisotropy metrics, and measurement location (anterior or posterior cervix) was a statistically significant predictor of speckle statistics metrics. CONCLUSION: This investigation was the first to present an analysis of speckle statistics in the in vivo human cervix in a longitudinal pregnancy study. It was shown that speckle statistics parameter estimates are sensitive to changes in the cervix as it progresses toward delivery, suggesting the clinical potential of these tools for detecting microstructural remodeling in the cervix.