title: In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model.
abstract: Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4-8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success.
authors: Department of Structural Mechanics, University of Granada, Granada, Spain.
authors: Laura
authors: L
authors: Peralta
authors: INRA, UMR 1198 Biologie du Développement et Reproduction, Jouy en Josas, France; PremUp foundation, 75006 Paris, France.
authors: Eve
authors: E
authors: Mourier
authors: INRA, UMR 1198 Biologie du Développement et Reproduction, Jouy en Josas, France; PremUp foundation, 75006 Paris, France.
authors: Christophe
authors: C
authors: Richard
authors: INRA, UMR 1198 Biologie du Développement et Reproduction, Jouy en Josas, France.
authors: Gilles
authors: G
authors: Charpigny
authors: INRA, UMR 703 APEX, Oniris, F-44307 Nantes, France.
authors: Thibaut
authors: T
authors: Larcher
authors: Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel UMR 7249, 13013 Marseille, France.
authors: Dora
authors: D
authors: Aït-Belkacem
authors: Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel UMR 7249, 13013 Marseille, France.
authors: Naveen K
authors: NK
authors: Balla
authors: Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel UMR 7249, 13013 Marseille, France.
authors: Sophie
authors: S
authors: Brasselet
authors: Institut Langevin, ESPCI ParisTech, CNRS, Université Paris Diderot - Paris 7, Paris, France.
authors: Mickael
authors: M
authors: Tanter
authors: Institut Langevin, ESPCI ParisTech, CNRS, Université Paris Diderot - Paris 7, Paris, France; Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina, United States of America.
authors: Marie
authors: M
authors: Muller
authors: INRA, UMR 1198 Biologie du Développement et Reproduction, Jouy en Josas, France; PremUp foundation, 75006 Paris, France.
authors: Pascale
authors: P
authors: Chavatte-Palmer
mesh_terms: D000818:Animals; D020070:Cervical Ripening / Q000502:physiology*; D002584:Cervix Uteri / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000648:ultrastructure*; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005260:Female; D007751:Labor, Induced / Q000379:methods*; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D023421:Models, Animal; D011247:Pregnancy; D011846:Radio Waves; D012756:Sheep
chemical_list: D003907:Dexamethasone; D003094:Collagen; D015232:Dinoprostone