Anisotropy and Spatial Heterogeneity in Quantitative Ultrasound Parameters: Relevance to the Study of the Human Cervix

Abstract

Imaging biomarkers based on quantitative ultrasound can offer valuable information about properties that inform tissue function and behavior such as microstructural organization (e.g., collagen alignment) and viscoelasticity (i.e., compliance). For example, the cervix feels softer as its microstructure remodels during pregnancy, an increase in compliance that can be objectively quantified with shear wave speed and therefore shear wave speed estimation is a potential biomarker of cervical remodeling. Other proposed biomarkers include parameters derived from the backscattered echo signal, such as attenuation and backscattered power loss, because such parameters can provide insight into tissue microstructural alignment and organization. Of these, attenuation values for the pregnant cervix have been reported, but large estimate variance reduces their clinical value. That said, parameter estimates based on the backscattered echo signal may be incorrect if assumptions they rely on, such as tissue isotropy and homogeneity, are violated. For that reason, we explored backscatter and attenuation parameters as potential biomarkers of cervical remodeling via careful investigation of the assumptions of isotropy and homogeneity in cervical tissue. Specifically, we estimated the angle- and spatial-dependence of parameters of backscattered power and acoustic attenuation in the ex vivo human cervix, using the reference phantom method and electronic steering of the ultrasound beam. We found that estimates are anisotropic and spatially heterogeneous, presumably because the tissue itself is anisotropic and heterogeneous. We conclude that appropriate interpretation of imaging biomarkers of cervical remodeling must account for tissue anisotropy and heterogeneity.

Quantitative Ultrasound Biomarkers Based on Backscattered Acoustic Power: Potential for Quantifying Remodeling of the Human Cervix during Pregnancy

“…Cervical softening is digitally palpable by 6-8 weeks of gestation (Danforth, 1983) and softness is one parameter used by clinicians to evaluate readiness of the cervix for The ability to objectively quantify cervical evaluation could improve prediction of delivery (pre-or post-term) and facilitate comprehensive understanding of the remodeling process, which could in turn elucidate novel targets for therapies to prevent abnormal timing. For this reason, noninvasive quantitative ultrasound (QUS) techniques for evaluating the cervix are currently under investigation (Carlson et al, 2015;Hernandez-Andrade et al, 2013;Molina et al, 2012;Muller et al, 2015;Peralta et al, 2015;McFarlin et al, 2010McFarlin et al, , 2006aMcFarlin et al, , 2015aLabyed et al, 2011;Feltovich et al, 2012;Carlson et al, 2014aCarlson et al, ,b, 2015Guerrero et al, 2018;Huang et al, 2016;Feltovich et al, 2010;McFarlin et al, 2006b).…”

“…Given this probable anisotropy, one might expect the SAC to show anisotropy, in other words, demonstrate angle-dependence of acoustic properties. In fact, it does; we have recently demonstrated in cervical tissue that the SAC, and a related parameter based on the backscattered echo signal, the mean backscattered power difference (mBSPD), demonstrate anisotropy (Guerrero et al, 2018).…”

Quantitative Ultrasound Parameters Based on the Backscattered Echo Power Signal as Biomarkers of Cervical Remodeling: A Longitudinal Study in the Pregnant Rhesus Macaque

“…Our initial studies involved using (nonpregnant) hysterectomy specimens to verify shear wave speed estimates (SWS) and backscatter parameters (e.g. mean backscattered power difference, mBSPD) with actual tissue microstructure examined via nonlinear optical microscopy imaging in both Rhesus (Guerrero, 2018) and women (Guerrero et al, 2018b). Subsequently, we demonstrated in vivo with SWS that the cervix progressively softens as pregnancy advances in the Rhesus (Rosado-Mendez et al, 2017, 2018 and that the human cervix is significantly softer in late, as opposed to early, pregnancy (Carlson et al, 2015(Carlson et al, , 2018.…”

“…Parameters which quantify the angle-dependence of backscattered power depend upon the angular range used in the analysis (Guerrero et al, 2017). In this study, as in our previous studies of the human cervix, (Guerrero et al, 2018b) we used a ±28° beam steering range for computing BSPD parameters. With the prototype linear array transducer used for these studies, this angular range allows estimation of mBSPD to adequate depths (1.4 cm) for these studies.…”

Quantitative Ultrasound Detects Smooth Muscle Activity at the Cervical Internal Os in Vitro

“…Power spectra were estimated using a multitaper method (Thomson 1982) with five tapers. Attenuation compensation in the samples was accomplished by using published median attenuation coefficient values from our previous study of the ex vivo human cervix (see Guerrero et al 2018).…”