Mechanical Properties Of Soft Tissues Research Articles

Association Between Pain in Knee Osteoarthritis and Mechanical Properties of Soft Tissue Around Knee Joint

Pain is the most significant symptom of knee osteoarthritis (OA), which seriously affects the quality of life of patients. However, the cause of pain, pain relief, and targeted treatment methods are still unclear. Based on the diversified characteristics of knee pain location, this study was aimed to explore the associations between knee pain location and the mechanical properties of soft tissues in patients with knee OA. Fifteen healthy participants and 55 patients with knee OA were recruited and divided into five groups: no pain, anterior superior pain, anterior inferior pain, medial pain, and lateral pain. The Young’s moduli of the muscles, tendons, and ligaments around the knee joint were measured by shear wave elastography (SWE), and the differences between the five groups of soft tissue material properties were compared in this study. The Young’s moduli of the quadriceps tendon (QT), patellar tendon (PT), medial collateral ligament (MCL), and lateral patellar retinaculum (LPR) were strongly associated with pain location and were significantly increased compared with the other four groups, respectively. In addition, the Young’s moduli of the remaining soft tissue were not associated with pain location, and did not change significantly compared with the other four groups. This study provides data reference for the mechanical properties of soft tissue of healthy people and patients with knee OA, and provides a theoretical basis for more targeted pain relief, treatment, and rehabilitation in knee OA.

A novel modeling approach for finite element human body models with high computational efficiency and stability: application in pedestrian safety analysis

The purpose of the current study was to develop and validate a finite element (FE) pedestrian model with high computational efficiency and stability using a novel modeling approach. Firstly, a novel modeling approach of using hollow structures (HS) to simulate the mechanical properties of soft tissues under impact loading was proposed and evaluated. Then, an FE pedestrian model was developed, employing this modeling approach based on the Total Human Model for Safety (THUMS) pedestrian model, named as THUMS-HS model. Finally, the biofidelity of the THUMS-HS model was validated against cadaver test data at both segment and full-body level. The results show that the proposed hollow structures can simulate the mechanical properties of soft tissues and the predictions of the THUMS-HS model show good agreement with the cadaver test data under impact loading. Simulations also prove that the THUMS-HS model has high computational efficiency and stability. The proposed modeling approach of using hollow structures to simulate the mechanical properties of soft tissues is plausible and the THUMS-HS model could be used as a valid, efficient and robust numerical tool for analysis of pedestrian safety in vehicle collisions.

The focal mechanical properties of normal and diseased porcine aortic valve tissue measured by a novel microindentation device

Cells sense and respond to the heterogeneous mechanical properties of their tissue microenvironment, with implications for the development of many diseases, including cancer, fibrosis, and aortic valve disease. Characterization of tissue mechanical heterogeneity on cellular length scales of tens of micrometers is thus important for understanding disease mechanobiology. In this study, we developed a low-cost bench-top microindentation system to readily map focal microscale soft tissue mechanical properties. The device was validated by comparison with atomic force microscopy nanoindentation of polyacrylamide gels. To demonstrate its utility, the device was used to measure the focal microscale elastic moduli of normal and diseased porcine aortic valve leaflet tissue. Consistent with previous studies, the fibrosa layer of intact leaflets was found to be 1.91-fold stiffer than the ventricularis layer, with both layers exhibiting significant heterogeneity in focal elastic moduli. For the first time, the microscale compressive moduli of focal proteoglycan-rich lesions in the fibrosa of early diseased porcine aortic valve leaflets were measured and found to be 2.44-fold softer than those of normal tissue. These data provide new insights into the tissue micromechanical environment in valvular disease and demonstrate the utility of the microindentation device for facile measurement of the focal mechanical properties of soft tissues.

Micromechanical poroelastic and viscoelastic properties of ex-vivo soft tissues

Soft biological tissues demonstrate strong time-dependent mechanical behavior, arising from their intrinsic viscoelasticity and fluid flow-induced poroelasticity. It is increasingly recognized that time-dependent mechanical properties of soft tissues influence their physiological functions and are linked to several pathological processes. Nevertheless, soft tissue time-dependent characteristics, especially their micromechanical variation with tissue composition and location, remain poorly understood. Nanoindentation is a well-established technique to measure local elastic properties but has not been fully explored to determine micro-scale time-dependent properties of soft tissues. Here, a nanoindentation-based experimental strategy is implemented to characterize the micro-scale poroelastic and viscoelastic behavior of mouse heart, kidney, and liver tissues. It is demonstrated that heart tissue exhibits substantial mechanical heterogeneity where the elastic modulus varies spatially from 1 to 30 kPa. In contrast, both kidney and liver tissues show relatively homogeneous response with elastic modulus 0.5–3 kPa. All three tissues demonstrate marked load relaxation under constant indentation, where the relaxation behavior is observed to be largely dominated by tissue viscoelasticity. Intrinsic permeability varies among different tissues, where heart tissue is found to be less permeable compared to kidney and liver tissues. Overall, the results presented herein provide key insights into the time-dependent micromechanical behavior of different tissues and can therefore contribute to studies of tissue pathology and tissue engineering applications.

Ultrasound Elastography for Lung Disease Assessment.

Ultrasound elastography (US-E) is a noninvasive, safe, cost-effective and reliable technique to assess the mechanical properties of soft tissue and provide imaging biomarkers for pathological processes. Many lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and interstitial lung disease are associated with dramatic changes in mechanical properties of lung tissues. Nevertheless, US-E is rarely used to image the lung because it is filled with air. The large difference in acoustic impedance between air and lung tissue results in the reflection of the ultrasound wave at the lung surface and, consequently, the loss of most ultrasound energy. In recent years, there has been an increasing interest in US-E applications in evaluating lung diseases. This article provides a comprehensive review of the technological advances of US-E research on lung disease diagnosis. We introduce the basic principles and major techniques of US-E and provide information on various applications in lung disease assessment. Finally, the potential applications of US-E to the diagnosis of COVID-19 pneumonia is discussed.

Dispersion curve calculation in viscoelastic tissue-mimicking materials using non-parametric, parametric, and high-resolution methods

Ultrasound shear wave elastography is a modality used for noninvasive, quantitative evaluation of soft tissue mechanical properties. A common way of exploring the tissue viscoelasticity is through analyzing the shear wave velocity dispersion curves. The variation of phase velocity with frequency or wavelength is called the dispersion curve. An increase of the available spectrum to be used for phase velocity estimation is meaningful for a tissue dispersion analysis in vivo. A number of available methods for dispersion relation estimation exist which can give diffuse results due the presence of noise in the measured data. In this work we compare six selected methods used for dispersion curve calculation in viscoelastic materials. Non-parametric, parametric and high-resolution methods were examined and compared. We tested selected methods on digital phantom data created using finite-difference-based method in tissue-mimicking viscoelastic media as well as on the experimental custom tissue-mimicking phantoms. In addition, we evaluated the algorithms with different levels of added white Gaussian noise to the shear wave particle velocity from numerical phantoms. Tests conducted showed that more advanced methods can offer better frequency resolution, and less variance than the fast Fourier transform. In addition, the non-parametric Blackman-Tukey approach exhibits similar performance and can be interchangeably used for shear wave phase velocity dispersion curves calculation.

A micromechanical model of tendon and ligament with crimped fibers

The mechanical properties of soft tissues are strongly dependent on their microstructures which evolve with aging and diseases. In this paper, a micromechanical model is presented to investigate the mechanical properties of tendons and ligaments, which are treated as planar crimped fiber-reinforced composites. The interaction among the constituents in such a composite is accounted for by utilizing the Mori–Tanaka method. Explicit analytical solutions are derived for describing the effects of microstructures on its macroscopic elastic properties, which are in good agreement with both finite element analysis and relevant experimental results. It is found that fiber waviness has a significant influence on the elastic properties of tendon and ligament. Our findings also demonstrate that planar crimp is significant to achieve the large Poisson's ratio of ligament and tendon, thereby revealing a novel structure–function mechanism. Parametric analysis further elucidates that their Poisson's ratios are also dependent on the volume fractions of crimped fibers and the elastic properties of the matrix. This work not only provides a theoretical method to predict the constitutive relation of biocomposites containing wavy fibers, but also expands our knowledge on the microstructural origin of large Poisson's ratios of soft tissues.

A parametric evaluation of shear wave speeds estimated with time-of-flight calculations in viscoelastic media.

Shear wave elasticity imaging (SWEI) uses an acoustic radiation force to generate shear waves, and then soft tissue mechanical properties are obtained by analyzing the shear wave data. In SWEI, the shear wave speed is often estimated with time-of-flight (TOF) calculations. To characterize the errors produced by TOF calculations, three-dimensional (3D) simulated shear waves are described by time-domain Green's functions for a Kelvin-Voigt model evaluated for multiple combinations of the shear elasticity and the shear viscosity. Estimated shear wave speeds are obtained from cross correlations and time-to-peak (TTP) calculations applied to shear wave particle velocities and shear wave particle displacements. The results obtained from these 3D shear wave simulations indicate that TTP calculations applied to shear wave particle displacements yield effective estimates of the shear wave speed if noise is absent, but cross correlations applied to shear wave particle displacements are more robust when the effects of noise and shear viscosity are included. The results also show that shear wave speeds estimated with TTP methods and cross correlations using shear wave particle velocities are more sensitive to increases in shear viscosity and noise, which suggests that superior estimates of the shear wave speed are obtained from noiseless or noisy shear wave particle displacements.

Print-A-Punch: A 3D printed device to cut dumbbell-shaped specimens from soft tissue for tensile testing

The failure behavior and mechanical properties of soft tissue can be characterized by conducting uniaxial tensile tests on small sectioned specimens, called test coupons. An ideal coupon geometry for tensile testing is a dumbbell shape (dog-bone), yet the cost and time required to fabricate custom steel punches to cut dumbbell-shaped coupons has hindered their universal application in biomechanics research. In this study, we developed an economical and reliable cutting device that can extract dumbbell-shaped coupons from soft biological tissue. The novel device, called Print-A-Punch, uses three-dimensional (3D) printed components in combination with standard fasteners and replaceable flexible razors. We identified design factors that influence the dimensional accuracy and symmetry of elastomer coupons extracted using this cutting device, and demonstrated its use on bovine meniscus. Advantages of this 3D printed device include a fast fabrication time, low material cost, good accuracy, replaceable blades, and an ability to scale coupon dimensions for specific tissues and experiments. By reducing the cost and time to cut accurate dumbbell-shaped coupons, this technology can facilitate the broad adoption of standard test methods that improve the quality and reproducibility of tensile tests in soft biological tissue. Researchers can freely download a set of STL files from this study to build their own Print-A-Punch device (https://boisestate.edu/coen-ntm/technology/print-a-punch).

Hyperelastic and viscoelastic characterization of hepatic tissue under uniaxial tension in time and frequency domain

In order to create accurate anatomical models for medical training and research, mechanical properties of biological tissues need to be studied. However, non-linear and viscoelastic behaviour of most soft biological tissues complicates the evaluation of their mechanical properties. In the current study, a method for measuring hyperelasticity and viscoelasticity of bovine and porcine hepatic parenchyma in tension is presented.First, non-linear stress–stretch curves resulting from ramp loading and unloading, were interpreted based on a hyperelastic framework, using a Veronda–Westmann strain energy function. Strain-specific elastic moduli, such as initial stiffness EI, were thereupon defined in certain parts of the stress–stretch curves. Furthermore, dissipated and stored energy density were calculated. Next, the viscoelastic nature of liver tissue was examined with two different methods: stress relaxation and dynamic cyclic testing. Both tests yielded dissipated and stored energy density, as well as loss tangent (tanδ), storage modulus (E′), and loss modulus (E′′). In tension, stress relaxation was experimentally more convenient than dynamic cyclic testing. Thus we considered whether relaxation could be used for approximating the results of the cyclic tests.Regarding the resulting elastic moduli, initial stiffness was similar for porcine and bovine liver (EI∼30kPa), while porcine liver was stiffer for higher strains. Comparing stress relaxation with dynamic cyclic testing, tanδ of porcine and bovine liver was the same for both methods (tanδ=0.05−0.25 at 1 Hz). Storage and loss moduli matched well for bovine, but not as well for porcine tissue.In conclusion, the utilized Veronda–Westmann model was appropriate for representing the hyperelasticity of liver tissue seen in ramp tests. Concerning viscoelasticity, both chosen testing methods – stress relaxation and dynamic cyclic testing – yielded comparable results for E′, E′′, and tanδ, as long as elasticity non-linearities were heeded.The here presented method provides novel insight into the tensile viscoelastic properties of hepatic tissue, and provides guidelines for convenient evaluation of soft tissue mechanical properties.

Fast Randomized Singular Value Decomposition-Based Clutter Filtering for Shear Wave Imaging

The mechanical properties of soft tissues can be quantitatively characterized through the estimation of shear wave velocity (SWV) using various motion estimation methods, such as the commonly used block matching (BM) methods. However, such methods suffer from slow computational speed and many tunable parameters. In order to solve these problems, Butterworth filter-based clutter filter wave imaging (BW-CFWI) is recently proposed to detect the mechanical wave propagation by highlighting the tissue velocity induced by mechanical wave, without using any motion estimation methods. In this study, in order to improve the SWV estimation performance of the clutter filter wave imaging (CFWI) method, we propose singular value decomposition (SVD)-based clutter filter for CFWI (SVD-CFWI) and further accelerate it using a randomized SVD (rSVD)-based clutter filter (rSVD-CFWI). Homogeneous phantoms with different Young's moduli are used to investigate the influences of the cutoff order of singular value and iteration time on the performance of SWV estimation. An elasticity phantom with stepped cylindrical inclusions is tested for comparison of rSVD-CFWI, SVD-CFWI, BW-CFWI, and normalized cross-correlation (NCC)-based BM (NCC-BM). The performances of the proposed methods are also evaluated on data acquired from the bicipital muscle in vivo. The results of phantom experiments show that rSVD-CFWI and SVD-CFWI reconstruct SWV maps with improved shape of the inclusions. For the softest inclusion with a diameter of 10.40 mm, the contrast-to-noise ratios (CNRs) between the inclusions and background obtained with rSVD-CFWI (3.78 dB) and SVD-CFWI (3.71 dB) are higher than those obtained with BW-CFWI (0.55 dB) and NCC-BM (0.70 dB). For the stiffest inclusion with a diameter of 10.40 mm, higher CNRs are also achieved by rSVD-CFWI (5.68 dB) and SVD-CFWI (5.07 dB) than by BW-CFWI (2.92 dB) and NCC-BM (2.36 dB). In the in-vivo experiments, more homogeneous SWV maps and smaller standard deviations of SWVs are obtained with rSVD-CFWI and SVD-CFWI than with BW-CFWI and NCC-BM. Besides, RSVD-CFWI has lower computational complexity than SVD-CFWI and NCC-BM and has lower memory space requirement than SVD-CFWI. The computational speed of rSVD-CFWI is comparable to that of BW-CFWI and over 10 times higher than that of SVD-CFWI. Therefore, RSVD-CFWI is demonstrated to be a competitive tool for fast shear wave imaging.

A Probing Device for Quantitatively Measuring the Mechanical Properties of Soft Tissues during Arthroscopy.

Probing in arthroscopic surgery is performed by pulling or pushing the soft tissue, which provides feedback for understanding the condition of the soft tissue. However, the output is only qualitative based on the "surgeon's feeling". Herein is described a probing device developed to address this issue by measuring the resistance of soft tissues quantitatively with a tri-axial force sensor. Under both conditions (i.e., pull- and push-probing certain tissues mimicking the acetabular labrum and cartilage), this probing device is found to be useful for measuring some mechanical properties in joints during arthroscopy.

A Probing Device for Quantitatively Measuring the Mechanical Properties of Soft Tissues during Arthroscopy

A Probing Device for Quantitatively Measuring the Mechanical Properties of Soft Tissues during Arthroscopy

Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro.

The mechanical properties of the cellular microenvironment play a crucial role in modulating cell function, and many pathophysiological processes are accompanied by variations in extracellular matrix (ECM) stiffness. Lysyl oxidase (LOx) is one of the enzymes involved in several ECM-stiffening processes. Here, we engineered poly(ethylene glycol) (PEG)-based hydrogels with controlled mechanical properties in the range typical of soft tissues. These hydrogels were functionalized featuring free primary amines, which allows an additional chemical LOx-responsive behavior with increase in crosslinks and hydrogel elastic modulus, mimicking biological ECM-stiffening mechanisms. Hydrogels with elastic moduli in the range of 0.5–4 kPa were obtained after a first photopolymerization step. The increase in elastic modulus of the functionalized and enzyme-responsive hydrogels was also characterized after the second-step enzymatic reaction, recording an increase in hydrogel stiffness up to 0.5 kPa after incubation with LOx. Finally, hydrogel precursors containing HepG2 (bioinks) were used to form three-dimensional (3D) in vitro models to mimic hepatic tissue and test PEG-based hydrogel biocompatibility. Hepatic functional markers were measured up to 7 days of culture, suggesting further use of such 3D models to study cell mechanobiology and response to dynamic variation of hydrogels stiffness. The results show that the functionalized hydrogels presented in this work match the mechanical properties of soft tissues, allow dynamic variations of hydrogel stiffness, and can be used to mimic changes in the microenvironment properties of soft tissues typical of inflammation and pathological changes at early stages (e.g., fibrosis, cancer).

"All-in-One" Gel System for Whole Procedure of Stem-Cell Amplification and Tissue Engineering.

Microsphere (MS)-based systems provides great advantages for cell expansion and transplantation due to their high surface-to-volume ratio and biomimetic environment. However, a MS-based system that includes cell attachment, proliferation, passage, harvest, cryopreservation, and tissue engineering together has not been realized yet. An "all-in-one" gel MS-based system is established for human adipose-derived mesenchymal stem cells (hADSCs), realizing real 3D culture with enhanced expansion efficiency and simplified serial cell culture operations, and construction of macrotissues with uniform cell distribution and specific function. A 3D digital light-processing technology is developed to fabricate gel MSs in an effective way. The printed MSs present a suitable environment with rough surface architecture and the mechanical properties of soft tissues, leading to high cell viability, attachment, proliferation, activity, and differentiation potential. Further, convenient standard operation procedures, including cell passage, detachment, and cryopreservation, are established for cell culture on the gel MSs. Finally, hADSCs-loaded gel MSs form macrotissues through a "bottom-up" approach, which demonstrates the potential applications for tissue engineering. These findings exhibit the feasibility and beauty of "all-in-one" stem cell culture and tissue engineering system.

Real-Time Nonlinear Characterization of Soft Tissue Mechanical Properties

Online soft tissue characterization is important for robotic-assisted minimally invasive surgery to achieve precise and stable robotic control with haptic feedback. This paper presents a new nonlinear recursive adaptive filtering methodology for online nonlinear soft tissue characterization. An adaptive unscented Kalman filter is developed based on the Hunt-Crossley model by windowing approximation to online estimate system and measurement noise covariances. To improve the accuracy of noise covariance estimations, a recursive formulation is subsequently developed for estimation of system and measurement noise covariances by introducing a weighting factor. This weighting factor is further modified to accommodate noise statistics of large variation which could be caused by rupture events and geometric discontinuities in robotic-assisted surgery. Simulations, experiments, and comparison analyses demonstrate that the proposed nonlinear recursive adaptive filtering methodology can characterize soft tissue parameters in the presence of system or measurement noise statistics in both small and large variations for robotic-assisted surgery. The proposed methodology can effectively estimate soft tissue parameters under system and measurement noises in both small and large variations, leading to improved filtering accuracy and robustness in comparison with UKF.

OpenMRE: A Numerical Platform for MRE Study

Magnetic resonance elastography (MRE) offers a noninvasive solution to visualize the mechanical properties of soft tissue, but the study suffers from expensive magnetic resonance scanning. Moreover, translating MRE wave images into soft tissue elasticity is a nontrivial issue for clinical professionals and healthcare practitioners. An interactive system-OpenMRE-is thus developed with the aid of ImageJ for numerical MRE study. It is comprised of two comparatively independent toolkits, namely MREA for simulation and MREP for interpretation. MREA mainly deals with the forward problem of MRE, and provides a numerical platform to determine the propagation and distribution of specially designed elastic wave. It is possible to numerically study some state-of-the-art paradigms including multisource and multifrequency MRE. The resultant wave images are interpretable in MREP that is designed for the inverse problem of MRE. It consists of the algorithms for phase unwrapping, directional filtering, and elasticity reconstruction. In a word, OpenMRE offers the MRE community a convenient and well-functioning system for interactive MRE study.

Estimation of depth-dependent material properties of biphasic soft tissues through finite element optimization and sensitivity analysis

A knowledge of material properties of soft tissue, such as articular cartilage, is essential to assess its mechanical function. It is also increasingly more evident that the inhomogeneity of the tissues plays a significant role in its in vivo functioning. Hence, efficient and reliable tools are needed to accurately characterize the inhomogeneity of the soft tissue mechanical properties. The objective of this research is to propose a finite element optimization procedure to determine depth-dependent material properties of articular cartilage by processing experimental data. Cartilage is modeled as a biphasic continuum with a linear elastic solid phase. The optimization method is based on a sensitivity analysis where the sensitivity of the finite element results to a variation in the material properties is analytically evaluated. The elastic modulus and permeability of the tissue are assumed to vary either linearly or quadratically through the thickness of the cartilage layer. After adopting some initial estimates, these material properties are updated iteratively based on their sensitivities to the current results, and the difference between the actual experimental data and computational experimental data. The optimization method has been tested in two common experimental configurations of cartilage and found to be efficient to estimate the material properties.

Ultrasound surface wave elastography for assessing extremity lymphedema: A pilot clinical study

Lymphedema is a condition in which protein-rich fluid accumulates in the tissue causing impaired limb function from swelling and stiffness. Understanding the mechanical properties of soft tissue in lymphedematous limbs is important in clinical diagnosis. We recently developed an ultrasound surface wave elastography (USWE) technique for measuring the shear wave speed of tissue. The aim of this study is to evaluate lymphedematous limb use USWE. A total of 11 patients with lymphedema were included. Both normal and affected extremities were measured. A 0.1-s harmonic vibration was generated by the indenter of the handheld shaker on the limb. Ultrasound probe was used for detecting the tissue motion. Shear wave speed of the tissue was measured using 2-D processing window technique. A region of interest was selected to measure superficial and deep fat tissues. The obtained results showed that the magnitudes of the wave speeds of both the superficial and deep fat tissue at lymphedema sites were statistically higher than those of the control sites, respectively. This suggests that USWE may be useful in assessing correlation between tissue stiffness and lymphedema and would enable physicians to monitor disease severity.

Passive elastography: Extracting mechanical properties of soft tissues from natural elastic waves

Clinical devices that give elastography imaging from a shear wave speed measurement within tissues uses controlled sources for elastic wave generation. It can be a mechanical vibrator for transient elastography and magnetic resonance elastography (MRE) or ultrasound radiation pressure for ARFI and shear wave elastography technique. Generally speaking, the main drawback of all these methods is the drop of efficiency for deep regions and obese patient. Delivering robust elastic waves in depth is an issue. We have proposed in the past a solution that avoid the problem of shear wave penetration using active sources. It consists in using natural shear waves that exist everywhere in living tissues. These natural shear wave are created thanks to heart beating, to pulse wave within arteries or to muscle activities. Since a few years now, we have been tracking natural shear waves in different soft tissues of the human body and we have not yet been disappointed. Using uncontrolled shear wave needs a change in the group velocity measurement paradigm. This approach is the so-called noise correlation technique developed in the field of seismology.