Laura Peralta

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.

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.

Mechanical assessment of cervical remodelling in pregnancy: insight from a synthetic model.

During the gestation and the cervical remodelling, several changes occur progressively in the structure of the tissue. An increase in the hydration, disorganisation of collagen network and decrease in elasticity can be observed. The collagen structure disorganisation is particularly complex: collagen fibres turn thicker and more wavy as the gestation progresses in a transition from relatively straight fibres to wavy fibres, while pores between collagen fibres become larger and separated. Shear wave elastography is a promising but not yet fully understood tool to assess these structural changes and the cervix׳s ability to dilate. To this end, a numerical histo-mechanical model is proposed in the present study, which aims at linking variations in the microscopic histo-biomechanical processes with shear wave propagation characteristics. Parametric simulations are carried out for a broad range of mechanical and geometrical parameters. Results show a direct relationship between the histological and morphological changes during pregnancy and the viscoelastic behaviour of the tissue.

Transient Elastography to Assess the Cervical Ripening during Pregnancy: A Preliminary Study.

Purposeu2002To explore the feasibility of transient elastography (TE) to quantify cervical stiffness changes during normal pregnancy and its spatial variability. Materials and Methodsu2002TE was used to quantify the cervical stiffness in four anatomical regions. 42 women between 17 and 43 years of age and at 6u200a-u200a41 weeks of gestation were studied. The stiffness was related to gestational age at the time of examination, interval from ultrasound examination toxa0delivery and cervical length to evaluate the potential of TE to assess cervical ripening. In addition, a sensitivity analysis based on Cronbachs alpha coefficient was carried out to assess the concordance between inter/intra-operator measurements. Resultsu2002There were significant correlations between cervical stiffness measured in the four regions with gestational age and the remaining time for delivery. Results confirm stiffness variability within the cervix. No significant association was found between cervical length and stiffness in the four ROIs. Associations between gestational age and remaining time for delivery with cervical length present weaker correlations than with cervical stiffness. The external part of the cervix was significantly softer than the internal one, and these stiffness values vary significantly in the anterior compared to the posterior cervix. The measurements taken by the same and by two different observers for different regions in the cervix were reliable and reproducible. Conclusionu2002It is feasible to objectively quantify the decrease of cervical stiffness correlated to gestational age. Transient elastography is a valuable promising tool to provide additional information on the process of cervical effacement to that obtained from digital examination and conventional ultrasound. Further studies are needed to assess the feasibility of the technique in obstetric clinical applications, such as prediction of preterm birth or success in labor induction.

Assessing viscoelasticity of shear wave propagation in cervical tissue by multiscale computational simulation.

The viscoelastic properties are recently being reported to be particularly sensitive to the gestation process, and to be intimately related to the microstructure of the cervical tissue. However, this link is not fully understood yet. In this work, we explore the importance of the heterogeneous multi-scale nature of cervical tissue for quantifying both elasticity and viscosity from shear waves velocity. To this end, shear wave propagations are simulated in a microscopic cervical tissue model using the finite difference time domain technique, over a wide frequency range from 15 to 200 kHz. Three standard rheological models (Voigt, Maxwell and Zener) are evaluated regarding their ability to reproduce the simulated dispersion curves, and their plausibility to describe cervical tissue is ranked by a stochastic model-class selection formulation. It is shown that the simplest model, i.e. that with less parameters, which best describes the simulated dispersion curves in cervical tissue is the Maxwell model. Furthermore, results show that the excitation frequency determines which rheological model can be representative for the tissue. Typically, viscoelastic parameters tend to converge for excitation frequencies over 100 kHz.

A STOCHASTIC MODEL FOR TISSUE CONSISTENCE EVOLUTION BASED ON THE INVERSE PROBLEM

An inverse-stochastic framework is proposed to reproduce the pattern evolution and predict the mechanical properties of a tissue-engineered culture from ultrasonic measurements in an in-vitro culture. A Markovian type of evolution is expected in tissue cultures for mechanical properties such us bulk modulus (K) or attenuation coefficient (AC), under the hypothesis that the future of the process depends only upon its present state, and not upon past states. Additionally a spread in the evolution histories for different repetitions of the same process is expected, consequently stochastic models such us Markov chains [Gallager, 1996] seems to be more suitable. The method proposed is predictive in nature and can be applicable to any measurable biomechanical process, under the assumption that the process shows Markovian evolution.

Model-based damage evaluation of layered CFRP structures

An ultrasonic evaluation technique for damage identification of layered CFRP structures is presented. This approach relies on a model-based estimation procedure that combines experimental data and simulation of ultrasonic damage-propagation interactions. The CFPR structure, a [0/90]4s lay-up, has been tested in an immersion through transmission experiment, where a scan has been performed on a damaged specimen. Most ultrasonic techniques in industrial practice consider only a few features of the received signals, namely, time of flight, amplitude, attenuation, frequency contents, and so forth. In this case, once signals are captured, an algorithm is used to reconstruct the complete signal waveform and extract the unknown damage parameters by means of modeling procedures. A linear version of the data processing has been performed, where only Young modulus has been monitored and, in a second nonlinear version, the first order nonlinear coefficient β was incorporated to test the possibility of detection of ea...

Single-transmitter setup on nonlinear mixing to measure acoustic nonlinearity of first order

In this study, the acoustic nonlinearity of water was investigated using a variation of the collinear wave mixing method. One single transducer, driven at two different frequencies f_a and f_b, was used to generate a third frequency component at f_a - f_b, f_a + f_b, 2f_a and 2f_b. Such a configuration allows to cancel out system nonlinearities since no amplification of the signal beyond 10V is needed. Perturbation solutions of nonlinear parameter in water are analytically calculated and validated with experimental measurements.

A MULTISCALE MECHANICAL MODEL FOR THE CERVICAL TISSUE

A multi-scale constitutive model for the nonpregnant cervical tissue is presented. The mechanical response of the cervix is described by a model which takes into account material properties at different structural hierarchies of tissue through a multi-scale coupling scheme. The model introduces the deformation mechanisms of collagen fibrils at the nanoscale into a macroscopic description of the mechanical behavior of tissue continuum. The composition of soft tissues like cervical tissue consists of a distribution of cells embedded in an extracellular matrix (ECM). The microstructure of cervical ECM is composed of dense, hydrated and highly cross-linked collagen network embedded in a viscous proteoglycan ground substance. The mechanical behavior of cervix can be largely due to different constituents of its extracellular matrix, and the collagen fibers are the major responsible for its mechanical strength [M. House, 2009]. So the proposed model considers the stroma as the maximum responsible for the mechanical strength of the cervix.