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.

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.

Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in plate-like media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment ( $$\hbox {NH}_\text {4}$$NH 4 OH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.

This paper presents the results of the comparison between a proposed Fourth Order Elastic Constants (FOECs) nonlinear model defined in the sense of Landau’s theory, and the two most contrasted hyperelastic models in the literature, Mooney–Rivlin, and Ogden models. A mechanical testing protocol is developed to investigate the large-strain response of ex vivo cervical tissue samples in uniaxial tension in its two principal anatomical locations, the epithelial and connective layers. The final aim of this work is to compare the reconstructed shear modulus of the epithelial and connective layers of cervical tissue. According to the obtained results, the nonlinear parameter A from the proposed FOEC model could be an important biomarker in cervical tissue diagnosis. In addition, the calculated shear modulus depended on the anatomical location of the cervical tissue (${\mu }_{epithelial}$ = 1.29 ± 0.15 MPa, and ${\mu }_{connective}$ = 3.60 ± 0.63 MPa).

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.

The clinical ultrasound community demands mechanisms to obtain the viscoelastic biomarkers of soft tissue in order to quantify the tissue condition and to be able to track its consistency. Torsional Wave Elastography (TWE) is an emerging technique proposed for interrogating soft tissue mechanical viscoelastic constants. Torsional waves are a particular configuration of shear waves, which propagate asymmetrically in-depth and are radially transmitted by a disc and received by a ring. This configuration is shown to be particularly efficient in minimizing spurious p-waves components and is sensitive to mechanical constants, especially in cylinder-shaped organs. The objective of this work was to validate (TWE) technique against Shear Wave Elasticity Imaging (SWEI) technique through the determination of shear wave velocity, shear moduli, and viscosity of ex vivo chicken liver samples and tissue mimicking hydrogel phantoms. The results of shear moduli for ex vivo liver tissue vary 1.69–4.0kPa using TWE technique and 1.32–4.48kPa using SWEI technique for a range of frequencies from 200 to 800Hz. Kelvin–Voigt viscoelastic parameters reported values of $\mu$ = 1.51kPa and $\eta$ = 0.54Pa·s using TWE and $\mu$ = 1.02kPa and $\eta$ = 0.63Pa·s using SWEI. Preliminary results show that the proposed technique successfully allows reconstructing shear wave velocity, shear moduli, and viscosity mechanical biomarkers from the propagated torsional wave, establishing a proof of principle and warranting further studies.