The adoption of multiscale approaches by the biomechanical community has caused a major improvement in quality in the mechanical characterization of soft tissues. The recent developments in elastography techniques are enabling in vivo and non-invasive quantification of tissues’ mechanical properties. Elastic changes in a tissue are associated with a broad spectrum of pathologies, which stems from the tissue microstructure, histology and biochemistry. This knowledge is combined with research evidence to provide a powerful diagnostic range of highly prevalent pathologies, from birth and labor disorders (prematurity, induction failures, etc.), to solid tumors (e.g., prostate, cervix, breast, melanoma) and liver fibrosis, just to name a few. This review aims to elucidate the potential of viscous and nonlinear elastic parameters as conceivable diagnostic mechanical biomarkers. First, by providing an insight into the classic role of soft tissue microstructure in linear elasticity; secondly, by understanding how viscosity and nonlinearity could enhance the current diagnosis in elastography; and finally, by compounding preliminary investigations of those elastography parameters within different technologies. In conclusion, evidence of the diagnostic capability of elastic parameters beyond linear stiffness is gaining momentum as a result of the technological and imaging developments in the field of biomechanics.

A novel torsional wave sensor designed to characterize mechanical properties of soft tissues is presented in this work. Elastography is a widely used technique since the 1990s to map tissue stiffness. Moreover, quantitative elastography uses the velocity of shear waves to achieve the shear stiffness. This technique exhibits significant limitations caused by the difficulty of the separation between longitudinal and shear waves and the pressure applied while measuring. To overcome these drawbacks, the proposed torsional wave sensor can isolate a pure shear wave, avoiding the possibility of multiple wave interference. It comprises a rotational actuator disk and a piezoceramic receiver ring circumferentially aligned. Both allow the transmission of shear waves that interact with the tissue before being received. Experimental tests are performed using tissue mimicking phantoms and cervical tissues. One contribution is a sensor sensitivity study that has been conducted to evaluate the robustness of the new proposed torsional wave elastography (TWE) technique. The variables object of the study are both the applied pressure and the angle of incidence sensor–phantom. The other contribution consists of a cervical tissue characterization. To this end, three rheological models have fit the experimental data and a static independent testing method has been performed. The proposed methodology permits the reconstruction of the mechanical constants from the propagated shear wave, providing a proof of principle and warranting further studies to confirm the validity of the results.

Pregnancy involves a gradual change in tissue consistency, where, as gestational age increases a drop in stiffness is noticeable. The extracellular matrix (ECM) of the cervix whose behavior is controlled by the collagen structure is reconfigured, due to hormonal and protein related factors that degraded it. There is an increase in cellular and water content. The collagen maintains a stable percentage, although the synthesis-solubility interaction causes a transformation in the network increasing its diameter and waviness, which destabilizes the mechanical integrity. Further understanding of the remodeling of the cervix becomes a key element in the progress against preterm birth. However, since the woman is in a very delicate state, the available information is scattered. The aim is to provide a framework where the variation of the histological properties is linked with the individual biomechanical evolution of the constituents; therefore a multiscale approach to the problem can be made. The results of different authors were reviewed to obtain values of each component depending on the gestational age, and then they were combined with the mechanical development of each variable obtained from the outputs of numerical simulations of another author. An additive function is proposed, in which the mechanical contribution of each constituent is added to a reference value established for a nonpregnant state. Results show how biochemistry models the mechanical behavior of the tissue through the histology and morphology of the ECM.

A torsional wave (TW) sensor prototype was employed to quantify stiffness of the cervix in pregnant women. A cross-sectional study in a total of 18 women between 16 weeks and 35 weeks + 5 days of gestation was performed. The potential of TW technique to assess cervical ripening was evaluated by the measurement of stiffness related to gestational age and cervical length. Statistically significant correlations were found between cervical stiffness and gestational age ( R 2 = 0.370 , p = 0.0074 , using 1 kHz waves and R 2 = 0.445 , p = 0.0250 , using 1.5 kHz waves). A uniform decrease in stiffness of the cervical tissue was confirmed to happen during the complete gestation. There was no significant correlation between stiffness and cervical length. A stronger association between gestational age and cervical stiffness was found compared to gestational age and cervical length correlation. As a conclusion, TW technique is a feasible approach to objectively quantify the decrease of cervical stiffness related to gestational age. Further research is required to evaluate the application of TW technique in obstetric evaluations, such as prediction of preterm delivery and labor induction failure.

The reconstruction of viscous properties of soft tissues, and more specifically, of cervical tissue is a challenging problem. In this paper, a new method is proposed to reconstruct the viscoelastic parameters of cervical tissue-mimicking phantoms by a Torsional Wave Elastography (TWE) technique. The reconstruction method, based on a Probabilistic Inverse Problem (PIP) approach, is presented and experimentally validated against Shear Wave Elastography (SWE). The anatomy of the cervical tissue has been mimicked by means of a two-layer gelatine phantom that simulates the epithelial and connective layers. Five ad hoc oil-in-gelatine phantoms were fabricated at different proportion to test the new reconstruction technique. The PIP approach was used for reconstructing the Kelvin-Voigt (KV) viscoelastic parameters by comparing the measurements obtained from the TWE technique with the synthetic signals from a Finite Difference Time Domain (FDTD) KV wave propagation model. Additionally, SWE tests were realized in order to characterize the viscoelastic properties of each batch of gelatine. Finally, validation was carried out by comparing the KV parameters inferred from the PIP with those reconstructed from the shear wave dispersion curve obtained from the SWE measurements. In order to test the degree of agreement between both techniques, a Student’s T-test and a Pearson’s correlation study were performed. The results indicate that the proposed method is able to reconstruct the KV viscoelastic properties of the cervical tissue, for both the epithelial and connective layers, as well as the thickness of the first layer with acceptable accuracy.

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Experimental evidence on testing a non-ultrasonic-based probe for a new approach in transluminal elastography was presented. The proposed modality generated shear waves by inducing oscillatory rotation on the lumen wall. Detection of the propagated waves was achieved at a set of receivers in mechanical contact with the lumen wall. The excitation element of the probe was an electromagnetic rotational actuator whilst the sensing element was comprised by a uniform anglewise arrangement of four piezoelectric receivers. The prototype was tested in two soft-tissue-mimicking phantoms that contained lumenlike conduits and stiffer inclusions. The shear wave speed of the different components of the phantoms was characterized using shear wave elastography. These values were used to estimate the time-of-flight of the expected reflections. Ultrafast ultrasound imaging, based on Loupas’ algorithm, was used to estimate the displacement field in transversal planes to the lumenlike conduit and to compare against the readouts from the transluminal transmission–reception tests. Experimental observations between ultrafast imaging and the transluminal probe were in good agreement, and reflections due to the stiffer inclusions were detected by the transluminal probe. The obtained experimental evidence provided proof-of-concept for the transluminal elastography probe and encouraged further exploration of clinical applications.

The WHO estimates that 15 million babies yearly (1 in 10) will be born preterm. Worldwide, complications of preterm births have supplanted pneumonia as the primary cause of child mortality [1]. The biology of cervical ripening that leads to birth is poorly understood, and there is no clinical tool to quantitatively evaluate the cervical biomechanical state, which in words of Feltovich [2]“… likely contributes to the reason the singleton spontaneous preterm birth rate has not changed appreciably in more than 100 years.” Towards this problem, we work on enabling new sensor technologies sentient to soft tissue biomechanics, to endow a new class of biomarkers that quantify the mechanical functionality of the cervix, and indeed any soft tissue, ranging pathologies from tumors, atherosclerosis, liver fibrosis to osteoarticular syndromes. Ultrasonic characterization of soft tissue has been developed as a clinical diagnostic tool [3] and evolved through different technologies including our torsional wave principle [4]. Our recent advances covering (a) torsional waves (shear elastic waves that propagate in quasifluids radially and in depth in a curled geometry), (b) sensors (based on a novel arrangement of concentric sandwiches of elements), (c) propagation models and (d) patient testing, are allowing to quantify the mechanical functionality beyond linear parameters: dispersive and nonlinear. [1] WHO, 2012; [2] Feltovich. AJOG207(2012):345–354 [3] Barr. Ultras Quart28(2012):13–20; [4] Melchor. Ultrasonics, 54(2014):1950–1962.