The objective of this proposal is to develop a quantitative ultrasound technique (acoustic radiation force impulse) to noninvasively and objectively assess cervical stiffness/softness. A key benefit of our work is that development of a method to measure cervical stiffness/softness alone could have significant impact;cervical softness is a critical, yet subjective, measure made daily in an obstetrics clinic. Our goal is to use such a tool to build a comprehensive understanding of cervical microstructure and how it changes throughout normal and abnormal pregnancy. We anticipate that an enhanced understanding of cervical microstructural changes will lead to targeted investigation of specific remodeling processes in pregnancy that will promote understanding of cervical insufficiency. This in turn could guide the exploration of novel therapeutic strategies.

Public Health Relevance

This is a proposal to develop quantitative ultrasound technology using acoustic radiation force impulse (ARFI) tools in ex vivo hysterectomy specimens in order to ultimately image and objectively quantify in vivo cervical softening in pregnancy. Cervical softening occurs throughout normal pregnancy but morbidity may occur when the cervix is too soft too early (preterm delivery) or too firm too late (postterm delivery). Currently, we have only subjective assessment of this important parameter. That alone makes objective quantification of cervical softening clinically useful. Even more, cervical softening is related to cervical microstructural arrangement and thus strength. The proposed effort involves (a) determining the sensitivity of ultrasound to the changes in stiffness/softness of the human cervix, (b) testing ARFI in isotropic and anisotropic phantoms as well as ex vivo cervical tissue in order to establish parameters for transition to in vivo cervical scanning, and (c) confirming through second harmonic generation microscopy the cervical microstructural changes that are associated with our ultrasound measurements. Besides providing an objective measure of a clinically useful parameter, development of a tool to quantify cervical softening should also give insight into cervical structure and function, including the dysfunction that leads to preterm delivery.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD063031-02
Application #
8117095
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (91))
Program Officer
Reddy, Uma M
Project Start
2010-07-25
Project End
2012-12-30
Budget Start
2011-07-01
Budget End
2012-12-30
Support Year
2
Fiscal Year
2011
Total Cost
$209,954
Indirect Cost
Name
University of Wisconsin Madison
Department
Physics
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Rosado-Mendez, Ivan M; Carlson, Lindsey C; Woo, Kaitlin M et al. (2018) Quantitative assessment of cervical softening during pregnancy in the Rhesus macaque with shear wave elasticity imaging. Phys Med Biol 63:085016
Guerrero, Quinton W; Feltovich, Helen; Rosado-Mendez, Ivan M et al. (2018) Anisotropy and Spatial Heterogeneity in Quantitative Ultrasound Parameters: Relevance to the Study of the Human Cervix. Ultrasound Med Biol 44:1493-1503
Guerrero, Quinton W; Feltovich, Helen; Rosado-Mendez, Ivan M et al. (2018) Quantitative Ultrasound Biomarkers Based on Backscattered Acoustic Power: Potential for Quantifying Remodeling of the Human Cervix during Pregnancy. Ultrasound Med Biol :
Feltovich, Helen (2017) Cervical Evaluation: From Ancient Medicine to Precision Medicine. Obstet Gynecol 130:51-63
Guerrero, Quinton W; Rosado-Mendez, Ivan M; Drehfal, Lindsey C et al. (2017) Quantifying Backscatter Anisotropy Using the Reference Phantom Method. IEEE Trans Ultrason Ferroelectr Freq Control 64:1063-1077
Rosado-Mendez, Ivan M; Palmeri, Mark L; Drehfal, Lindsey C et al. (2017) Assessment of Structural Heterogeneity and Viscosity in the Cervix Using Shear Wave Elasticity Imaging: Initial Results from a Rhesus Macaque Model. Ultrasound Med Biol 43:790-803
Feltovich, Helen; Carlson, Lindsey (2017) New techniques in evaluation of the cervix. Semin Perinatol 41:477-484
Vink, Joy; Feltovich, Helen (2016) Cervical etiology of spontaneous preterm birth. Semin Fetal Neonatal Med 21:106-12
Huang, Bin; Drehfal, Lindsey Carlson; Rosado-Mendez, Ivan M et al. (2016) Estimation of Shear Wave Speed in the Rhesus Macaques' Uterine Cervix. IEEE Trans Ultrason Ferroelectr Freq Control 63:1243-52
Rosado-Mendez, Ivan M; Drehfal, Lindsey C; Zagzebski, James A et al. (2016) Analysis of Coherent and Diffuse Scattering Using a Reference Phantom. IEEE Trans Ultrason Ferroelectr Freq Control 63:1306-20

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