Mechanical Properties Of Soft Tissues Research Articles

Ultrasound Shear Elastography With Expanded Bandwidth (USEWEB): A Novel Method for 2D Shear Phase Velocity Imaging of Soft Tissues.

Ultrasound shear wave elastography (SWE) is a noninvasive approach for evaluating mechanical properties of soft tissues. In SWE either group velocity measured in the time-domain or phase velocity measured in the frequency-domain can be reported. Frequency-domain methods have the advantage over time-domain methods in providing a response for a specific frequency, while time-domain methods average the wave velocity over the entire frequency band. Current frequency-domain approaches struggle to reconstruct SWE images over full frequency bandwidth. This is especially important in the case of viscoelastic tissues, where tissue viscoelasticity is often studied by analyzing the shear wave phase velocity dispersion. For characterizing cancerous lesions, it has been shown that considerable biases can occur with group velocity-based measurements. However, using phase velocities at higher frequencies can provide more accurate evaluations. In this paper, we propose a new method called Ultrasound Shear Elastography with Expanded Bandwidth (USEWEB) used for two-dimensional (2D) shear wave phase velocity imaging. We tested the USEWEB method on data from homogeneous tissue-mimicking liver fibrosis phantoms, custom-made viscoelastic phantom measurements, phantoms with cylindrical inclusions experiments, and in vivo renal transplants scanned with a clinical scanner. We compared results from the USEWEB method with a Local Phase Velocity Imaging (LPVI) approach over a wide frequency range, i.e., up to 200-2000 Hz. Tests carried out revealed that the USEWEB approach provides 2D phase velocity images with a coefficient of variation below 5% over a wider frequency band for smaller processing window size in comparison to LPVI, especially in viscoelastic materials. In addition, USEWEB can produce correct phase velocity images for much higher frequencies, up to 1800 Hz, compared to LPVI, which can be used to characterize viscoelastic materials and elastic inclusions.

Recent Development of Implantable Chemical Sensors Utilizing Flexible and Biodegradable Materials for Biomedical Applications.

Implantable chemical sensors built with flexible and biodegradable materials exhibit immense potential for seamless integration with biological systems by matching the mechanical properties of soft tissues and eliminating device retraction procedures. Compared with conventional hospital-based blood tests, implantable chemical sensors have the capability to achieve real-time monitoring with high accuracy of important biomarkers such as metabolites, neurotransmitters, and proteins, offering valuable insights for clinical applications. These innovative sensors could provide essential information for preventive diagnosis and effective intervention. To date, despite extensive research on flexible and bioresorbable materials for implantable electronics, the development of chemical sensors has faced several challenges related to materials and device design, resulting in only a limited number of successful accomplishments. This review highlights recent advancements in implantable chemical sensors based on flexible and biodegradable materials, encompassing their sensing strategies, materials strategies, and geometric configurations. The following discussions focus on demonstrated detection of various objects including ions, small molecules, and a few examples of macromolecules using flexible and/or bioresorbable implantable chemical sensors. Finally, we will present current challenges and explore potential future directions.

Development of a testing machine for biaxial testing of soft tissue and biomaterials

Knowledge of the mechanical properties of soft tissues and biomaterials is the keystone for predictive modeling in cardio- and endovascular surgery, traumatology and orthopedics, neurosurgery, and the development of tissue-engineering constructs. Needed mechanical properties can be only explored via experimental tests. Therefore, mechanical experiments are forming the foundation of medical decision support systems, which are impossible without adequate mathematical models of the processes involved. Sirius University of Science and Technology has launched the project "Experimental research and mathematical modeling of the mechanical behavior of biomaterials". The goal of the project is to create an infrastructure for experimental study of the mechanics of soft tissues and biomaterials. At this stage, a machine for biaxial testing of soft tissues and biomaterials has been developed and put into trial operation. The developed machine takes into account the features of working with soft tissues: small sample size, maintaining certain environmental conditions to preserve the sample, various types of sample gripping to minimize edge effects and no slippage, non-contact methods for assessing displacement and deformation fields, variability in sample loading protocols. The result of the test is a data set that includes a test report and synchronized output readings of strain gauge, temperature, optoelectronic sensors with high-resolution images. Uniaxial verification tests of acrylic tapes VHB4910 were carried out by the developed machine. The results were compared with data obtained on a commercial dynamic mechanical analyzer RSA-G2 (TA Instruments) for similar materials under the same test conditions. A series of biaxial cyclic experiments were carried out for the pericardium of cattle, the cardiovascular patch Ecofolon PS04/PS01 (JSC NPK Ecoflon, St. Petersburg, Russia), and the GoreTex vascular graft (W.L. Gore and Associates, USA).

Augmentation of musculoskeletal soft tissue morphology within low back pain patients may suggest the presence of physiological stress shielding: An in vivo study

IntroductionThe pathomechanism of low back pain (LBP) remains unknown. However, changes to mechanical properties of soft tissues affected by LBP may indicate the presence of stress shielding, which may manifest via tissue remodeling. This study investigates the potential for physiological stress shielding within the lumbar spine by examining differences within lumbar soft tissue morphology between control and LBP subjects. MethodsThrough MRI, the total and functional cross-sectional area (tCSA, fCSA) and fatty infiltration (FI) of the lumbar multifidus (MF), erector spinae (ES), quadratus lumborum (QL), psoas major (PM), and thoracolumbar fascia (TLF) were measured from the L1/L2 to L5/S1 intervertebral disc levels of 69 subjects (36 LBP and 33 control subjects). Statistical analysis was conducted using Mann-Whitney U. P < 0.05 denoted significance. ResultsComparison of male LBP patients and male healthy controls yielded an increase in tCSA and fCSA within the L4/L5 PM (p < 0.01), and the L4/L5 ES (p = 0.02) and PM (p < 0.01), respectively, of LBP patients. Female LBP patients’ FI compared to female controls increased within the L1/L2 MF (p = 0.03), L3/L4 MF (p = 0.04) and ES (p = 0.02), and L4/L5 QL (p = 0.01). The L3/L4 TLF also demonstrated an 8% increase in LBP subjects. ConclusionMale patients’ results suggest elevated tissue loading during motion yielding hypertrophy in the L4/L5 ES and PM fCSA, and PM tCSA. Female LBP patients’ MF, ES, and PM at L3/L4 demonstrating elevated FI coupled with TLF tCSA hypertrophy may suggest irregular stress distributions and lay the foundation for stress shielding within musculoskeletal soft tissues.

The effect of breathing on the in vivo mechanical characterization of linea alba by ultrasound shearwave elastography

The most common surgical repair of abdominal wall hernia consists in implanting a mesh to reinforce hernia defects during the healing phase. Ultrasound shearwave elastography (SWE) is a promising non-invasive method to estimate soft tissue mechanical properties at bedside through shear wave speed (SWS) measurement. Combined with conventional ultrasonography, it could help the clinician plan surgery. In this work, a novel protocol is proposed to reliably assess the stiffness of the linea alba, and to evaluate the effect of breathing and of inflating the abdomen on SWS.Fifteen healthy adults were included. SWS was measured in the linea alba, in the longitudinal and transverse direction, during several breathing cycle and during active abdominal inflation.SWS during normal breathing was 2.3 [2.0; 2.5] m/s in longitudinal direction and 2.2 [1.9; 2.7] m/s in the transversal. Inflating the abdomen increased SWS both in longitudinal and transversal direction (3.5 [2.8; 5.8] m/s and 5.2 [3.0; 6.0] m/s, respectively). The novel protocol significantly improved the reproducibility relative to the literature (8% in the longitudinal direction and 14% in the transverse one). Breathing had a mild effect on SWS, and accounting for it only marginally improved the reproducibility.This study proved the feasibility of the method, and its potential clinical interest. Further studies on larger cohort should focus on improving our understanding of the relationship between abdominal wall properties and clinical outcomes, but also provide a cartography of the abdominal wall, beyond the linea alba.

Rapid, non-invasive, in vivo measurement of tissue mechanical properties using gravitational loading and a nonlinear virtual fields method.

Measuring the mechanical properties of soft tissues in vivo is important in biomechanics and for diagnosis and staging of diseases, but challenging because it is difficult to control the boundary conditions. We present a novel, non-invasive method for measuring tissue properties using gravitational loading. MRI images of an organ in different positions are registered to measure tissue displacements due to gravitational forces in different positions. Considering equilibrium between stresses and gravity, we established a nonlinear virtual fields method to identify the tissue properties. The method was applied to the human brain as a proof of concept, using an Ogden model. Sensitivity analysis showed that the bulk modulus could be identified accurately while the shear modulus was identified with greater uncertainty; the strains were too small to identify the strain stiffening exponent. The measured properties agreed well with published in vitro data. The technique offers very promising perspectives, allowing the non-invasive measurement of otherwise inaccessible tissues and providing new information such as the bulk modulus under static loading, which has never previously been measured in vivo.

Multiscale mechanical analysis of the elastic modulus of skin

The mechanical properties of the skin determine tissue function and regulate dermal cell behavior. Yet measuring these properties remains challenging, as evidenced by the large range of elastic moduli reported in the literature—from below one kPa to hundreds of MPa. Here, we reconcile these disparate results by dedicated experiments at both tissue and cellular length scales and by computational models considering the multiscale and multiphasic tissue structure. At the macroscopic tissue length scale, the collective behavior of the collagen fiber network under tension provides functional tissue stiffness, and its properties determine the corresponding elastic modulus (100–200 kPa). The compliant microscale environment (0.1–10 kPa), probed by atomic force microscopy, arises from the ground matrix without engaging the collagen fiber network. Our analysis indicates that indentation-based elasticity measurements, although probing tissue properties at the cell-relevant length scale, do not assess the deformation mechanisms activated by dermal cells when exerting traction forces on the extracellular matrix. Using dermal-equivalent collagen hydrogels, we demonstrate that indentation measurements of tissue stiffness do not correlate with the behavior of embedded dermal fibroblasts. These results provide a deeper understanding of tissue mechanics across length scales with important implications for skin mechanobiology and tissue engineering. Statement of SignificanceMeasuring the mechanical properties of the skin is essential for understanding dermal cell mechanobiology and designing tissue-engineered skin substitutes. However, previous results reported for the elastic modulus of skin vary by six orders of magnitude. We show that two distinct deformation mechanisms, related to the tension–compression nonlinearity of the collagen fiber network, can explain the large variations in elastic moduli. Furthermore, we show that microscale indentation, which is frequently used to assess the stiffness perceived by cells, fails to engage the fiber network, and therefore cannot predict the behavior of dermal fibroblasts in stiffness-tunable fibrous hydrogels. This has important implications for how to measure and interpret the mechanical properties of soft tissues across length scales.

New Mechanical Markers for Tracking the Progression of Myocardial Infarction.

The mechanical properties of soft tissues can often be strongly correlated with the progression of various diseases, such as myocardial infarction (MI). However, the dynamic mechanical properties of cardiac tissues during MI progression remain poorly understood. Herein, we investigate the rheological responses of cardiac tissues at different stages of MI (i.e., early-stage, mid-stage, and late-stage) with atomic force microscopy-based microrheology. Surprisingly, we discover that all cardiac tissues exhibit a universal two-stage power-law rheological behavior at different time scales. The experimentally found power-law exponents can capture an inconspicuous initial rheological change, making them particularly suitable as markers for early-stage MI diagnosis. We further develop a self-similar hierarchical model to characterize the progressive mechanical changes from subcellular to tissue scales. The theoretically calculated mechanical indexes are found to markedly vary among different stages of MI. These new mechanical markers are applicable for tracking the subtle changes of cardiac tissues during MI progression.

Could Effective Mechanical Properties of Soft Tissues and Biomaterials at Mesoscale be Obtained by Modal Analysis?

Could Effective Mechanical Properties of Soft Tissues and Biomaterials at Mesoscale be Obtained by Modal Analysis?

Relationship between morphometric and mechanical properties of superficial lumbosacral soft tissue layers in healthy young adults.

Introduction: It is commonly considered that myotonometry is a non-invasive method capable of quantifying linear elastic and viscoelastic properties of the myofascial tissue through the application of a weak mechanical impulse to the surface of the skin. However, before the impulse can reach the myofascial tissue, it must cross more superficial tissues such as the skin and subcutaneous tissue (ST). All these superficial tissues have different distributions and organizations of structural components. Therefore, the study aimed to examine the potential relationships between the mechanical and morphometric properties of various superficial soft tissues surrounding the lumbar multifidus muscle (LM). Methods: Myotonometric measurements of dynamic stiffness, logarithmic decrement, and creep, and ultrasonographic measurements of thickness and echogenicity of cutaneous, subcutaneous, perimuscular tissue, and LM were obtained from 50 healthy individuals in the resting prone position and during contralateral arm lift. Results: The most important findings were that in both the relaxed and contracted LM state, the dynamic stiffness strongly negatively (r = -0.69; p < 0.001 in relaxation, r = -0.83; p < 0.001 in contraction) and creep strongly positively (r = 0.79; p < 0.001 in relaxation, r = 0.85; p < 0.001 in contraction) correlated with the thicknesses of the ST. Similar but weaker correlations were noticed between both these measures and the perimuscular tissue thickness. Elasticity was uncorrelated to the thicknesses of the tissues. With LM contraction (change from the relaxed to contracted state), the relative increase in dynamic stiffness was correlated with the relative decrease in dermis (r = -0.51; p < 0.001) and ST (r = -0.47; p = 0.001) thickness, and with the relative increase in LM (r = 0.36; p = 0.010) thickness. Moreover, the relative decrease (thinning) in the ST thickness was correlated with the relative increase in logarithmic decrement (i.e., decrease in soft tissue elasticity, r = -0.37, p = 0.011). The mechanical properties of the soft tissues were not related to their echogenicity. Discussion: In conclusion, the thicker the subcutaneous and perimuscular layers, the lesser the stiffness and the greater the time-dependent deformation to the external force of the tissues surrounding the LM during its relaxation and isometric contraction. Moreover, the greater the thinning of the ST and the thickening of the LM during its contraction, the higher the increase in lumbosacral tissue stiffness and the decrease in elasticity. Therefore, one should consider the thickness of the ST before planning or analyzing the outcomes of myotonometric or other external biomechanical measurements to avoid drawing the wrong conclusions about the mechanical properties of the myofascial tissue.

Single and bi-compartment poro-elastic model of perfused biological soft tissues: FEniCSx implementation and tutorial

Soft biological tissues demonstrate strong time-dependent and strain-rate mechanical behavior, arising from their intrinsic visco-elasticity and fluid–solid interactions. The time-dependent mechanical properties of soft tissues influence their physiological functions and are related to several pathological processes. Poro-elastic modeling represents a promising approach because it allows the integration of multiscale/multiphysics data to probe biologically relevant phenomena at a smaller scale and embeds the relevant mechanisms at the larger scale. The implementation of multiphase flow poro-elastic models however is a complex undertaking, requiring extensive knowledge. The open-source software FEniCSx Project provides a novel tool for the automated solution of partial differential equations by the finite element method. This paper aims to provide the required tools to model the mixed formulation of poro-elasticity, from the theory to the implementation, within FEniCSx. Several benchmark cases are studied. A column under confined compression conditions is compared to the Terzaghi analytical solution, using the L2-norm. An implementation of poro-hyper-elasticity is proposed. A bi-compartment column is compared to previously published results (Cast3m implementation). For all cases, accurate results are obtained in terms of a normalized Root Mean Square Error (RMSE). Furthermore, the FEniCSx computation is found three times faster than the legacy FEniCS one. The benefits of parallel computation are also highlighted.

Characterisation of the soft tissue viscous and elastic properties using ultrasound elastography and rheological models: validation and applications in plantar soft tissue assessment

Objective. The mechanical behaviour of soft tissue is influenced by its elastic and viscous characteristics. Therefore, the aim of this study was to develop a validated method to characterise the viscoelastic properties of soft tissues based on ultrasound elastography data. Approach. Plantar soft tissue was chosen as the tissue of interest, and gelatine-phantoms replicating its mechanical properties were manufactured for validation of the protocol. Both plantar soft tissue and the phantom were scanned using Reverberant shear wave ultrasound (US) elastography at 400–600 Hz. Shear wave speed was estimated using the US particle velocity data. The viscoelastic parameters were extracted by fitting the Young’s modulus as a function of frequency derived from the constitutive equations of the eight rheological models (four classic and their fractional-derivative versions) to the shear wave dispersion data. Furthermore, stress-time functions derived from the eight rheological models were fitted to the phantom stress-relaxation data. Main results. The viscoelastic parameters estimated using elastography data based on the fractional-derivative (FD) models, compared to the classic models, were closer to those quantified using the mechanical test. In addition, the FD-Maxwell and FD-Kelvin–Voigt models showed to more effectively replicate the viscoelastic behaviour of the plantar soft tissue with minimum number of model parameters ( = 0.72 for both models) . Hence the FD-KV and FD-Maxwell models can more effectively quantify the viscoelastic characteristics of the soft tissue compared to other models. Significance. In this study, a method for mechanical characterisation of the viscoelastic properties of soft tissue in ultrasound elastography was developed and fully validated. An investigation into the most valid rheological model and its applications in plantar soft tissue assessment were also presented. This proposed approach for the characterisation of viscous and elastic mechanical properties of soft tissue has implications in assessing the soft tissue function where those can be used as markers for diagnosis or prognosis of tissue status.

A MECHANICAL APPROACH FOR THE ASSESSMENT OF COMPARTMENT SYNDROME

In this work, we propose a new quantitative way of evaluating acute compartment syndrome (ACS) by dynamic mechanical assessment of soft tissue changes. First, we have developed an animal model of ACS to replicate the physiological changes during the condition. Secondly, we have developed a mechanical assessment tool for quantitative pre-clinical assessment of ACS. Our hand-held indentation device provides an accurate method for investigations into the local dynamic mechanical properties of soft tissue and for in-situ non-invasive assessment and monitoring of ACS.Our compartment syndrome model was developed on the cranial tibial and the peroneus tertius muscles of a pig's leg (postmortem). The compartment syndrome pressure values were obtained by injecting blood from the bone through the muscle.To enable ACS assessment by a hand-held indentation device we combined three main components: a load cell, a linear actuator and a 3-axis accelerometer. Dynamic tests were performed at a frequency of 0.5 Hz and by applying an amplitude of 0.5 mm.Another method used to observe the differences in the mechanical properties inside the leg was a 3D Digital Image Correlation (3D-DIC). Videos were taken from two different positions of the pig's leg at different pressure values: 0 mmHg, 15 mmHg and 40 mmHg. Two strains along the x axis (Exx) and y axis (Eyy) were measured.Between the two pressure cases (15 mmHg and 40 mmHg) a clear deformation of the model is visible. In fact, the bigger the pressure, the more visible the increase in strain is.In our animal model, local muscle pressures reached values higher than 40 mmHg, which correlate with observed human physiology in ACS. In our presentation we will share our dynamic indentation results on this model to demonstrate the sensitivity of our measurement techniques.Compartment syndrome is recognised as needing improved clinical management tools. Our approach provides both a model that reflects physiological behaviour of ACS, and a method for in-situ non-invasive assessment and monitoring.

3D-Printed multi-material liver model with simultaneous mechanical and radiological tissue-mimicking features for improved realism.

89Anatomic models have an important role in the medical domain. However, soft tissue mechanical properties' representation is limited in mass-produced and 3D-printed models. In this study, a multi-material 3D printer was used to print a human liver model featuring tuned mechanical and radiological properties, with the goal of comparing the printed model with its printing material and real liver tissue. The main target was mechanical realism, while radiological similarity was a secondary objective. Materials and internal structure were selected such that the printed model would resemble liver tissue in terms of tensile properties. The model was printed at 33% scaling and 40% gyroid infill with a soft silicone rubber, and silicone oil as a filler fluid. After printing, the liver model underwent CT scanning. Since the shape of the liver is incompatible with tensile testing, tensile testing specimens were also printed. Three replicates were printed with the same internal structure as the liver model and three more out of silicone rubber with 100% rectilinear infill to allow a comparison. All specimens were tested in a four-step cyclic loading test protocol to compare elastic moduli and dissipated energy ratios. The fluid-filled and full-silicone specimens had initial elastic moduli of 0.26 MPa and 0.37 MPa, respectively, and featured dissipated energy ratios of 0.140, 0.167, 0.183, and 0.118, 0.093, 0.081, respectively, in the second, third, and fourth loading cycles. The liver model showed 225 ± 30 Hounsfield units (HU) in CT, which is closer to real human liver (70 ± 30 HU) than the printing silicone (340 ± 50 HU). Results suggest that the liver model became more realistic in terms of mechanical and radiological properties with the proposed printing approach as opposed to printing only with silicone rubber. Thus, it has been demonstrated that this printing method enables new customization opportunities in the field of anatomic models.

Soft tissue characterization by dynamic impact analysis: Results on agar-based phantoms

The mechanical characterization of soft tissues is of great importance in different medical fields since a change of soft tissue properties may be of physio-pathologic nature. This study investigates the feasibility of using impact analysis to measure the mechanical properties of soft tissue mimicking phantoms made of agarose. The impact analysis is performed on agar-based specimens with various concentrations by applying small impacts on a beam in contact with the surface of the specimen. The time variation of the signal corresponding to the impact force is analyzed as a function of the agar concentration and the impact force amplitude. A temporal indicator τ is developed, corresponding to the time difference between the initial impact and the rebound of the beam on the hammer. The results show a decrease of τ when the agar concentration increases. The method appears to be sensitive to non-linear phenomena related to the material behavior and/or to contact phenomena between the beam and the specimen. The error on the estimation of the percentage of agar is of the same order of magnitude than the sensitivity obtained using elastography techniques. This study opens new perspective for fast, cheap, and non-invasive mechanical characterization of non-linear soft tissues.

Rate- and Region-Dependent Mechanical Properties of Göttingen Minipig Brain Tissue in Simple Shear and Unconfined Compression.

Traumatic brain injury (TBI), particularly from explosive blasts, is a major cause of casualties in modern military conflicts. Computational models are an important tool in understanding the underlying biomechanics of TBI but are highly dependent on the mechanical properties of soft tissue to produce accurate results. Reported material properties of brain tissue can vary by several orders of magnitude between studies, and no published set of material parameters exists for porcine brain tissue at strain rates relevant to blast. In this work, brain tissue from the brainstem, cerebellum, and cerebrum of freshly euthanized adolescent male Göttingen minipigs was tested in simple shear and unconfined compression at strain rates ranging from quasi-static (QS) to 300 s-1. Brain tissue showed significant strain rate stiffening in both shear and compression. Minimal differences were seen between different regions of the brain. Both hyperelastic and hyper-viscoelastic constitutive models were fit to experimental stress, considering data from either a single loading mode (unidirectional) or two loading modes together (bidirectional). The unidirectional hyper-viscoelastic models with an Ogden hyperelastic representation and a one-term Prony series best captured the response of brain tissue in all regions and rates. The bidirectional models were generally able to capture the response of the tissue in high-rate shear and all compression modes, but not the QS shear. Our constitutive models describe the first set of material parameters for porcine brain tissue relevant to loading modes and rates seen in blast injury.

A Bayesian constitutive model selection framework for biaxial mechanical testing of planar soft tissues: Application to porcine aortic valves

A variety of constitutive models have been developed for soft tissue mechanics. However, there is no established criterion to select a suitable model for a specific application. Although the model that best fits the experimental data can be deemed the most suitable model, this practice often can be insufficient given the inter-sample variability of experimental observations. Herein, we present a Bayesian approach to calculate the relative probabilities of constitutive models based on biaxial mechanical testing of tissue samples. Forty-six samples of porcine aortic valve tissue were tested using a biaxial stretching setup. For each sample, seven ratios of stresses along and perpendicular to the fiber direction were applied. The probabilities of eight invariant-based constitutive models were calculated based on the experimental data using the proposed model selection framework. The calculated probabilities showed that, out of the considered models and based on the information available through the utilized experimental dataset, the May–Newman model was the most probable model for the porcine aortic valve data. When the samples were further grouped into different cusp types, the May–Newman model remained the most probable for the left- and right-coronary cusps, whereas for non-coronary cusps two models were found to be equally probable: the Lee–Sacks model and the May–Newman model. This difference between cusp types was found to be associated with the first principal component analysis (PCA) mode, where this mode’s amplitudes of the non-coronary and right-coronary cusps were found to be significantly different. Our results show that a PCA-based statistical model can capture significant variations in the mechanical properties of soft tissues. The presented framework is applicable to other tissue types, and has the potential to provide a structured and rational way of making simulations population-based.

Ex vivo bovine liver nonlinear viscoelastic properties: MR elastography and rheological measurements

IntroductionKnowledge of the nonlinear viscoelastic properties of the liver is important, but the complex tissue behavior outside the linear viscoelastic regime has impeded their characterization, particularly in vivo. Combining static compression with magnetic resonance (MR) elastography has the potential to be a useful imaging method for assessing large deformation mechanical properties of soft tissues in vivo. However, this remains to be verified. Therefore this study aims first to determine whether MR elastography can measure the nonlinear mechanical properties of ex vivo bovine liver tissue under varying levels of uniform and focal preloads (up to 30%), and second to compare MR elastography-derived complex shear modulus with standard rheological measurements. MethodNine fresh bovine livers were collected from a local abattoir, and experiments were conducted within 12hr of death. Two cubic samples (∼10 × 10 × 10 cm3) were dissected from each liver and imaged using MR elastography (60 Hz) under 4 levels of uniform and focal preload (1, 10, 20, and 30% of sample width) to investigate the relationship between MR elastography-derived complex shear modulus (G∗) and the maximum principal Right Cauchy Green Strain (C11). Three tissue samples from each of the same 9 livers underwent oscillatory rheometry under the same 4 preloads (1, 10, 20, and 30% strain). MR elastography-derived complex shear modulus (G∗) from the uniform preload was validated against rheometry by fitting the frequency dependence of G∗ with a power-law and extrapolating rheometry-derived G∗ to 60 Hz. ResultsMR elastography-derived G∗ increased with increasing compressive large deformation strain, and followed a power-law curve (G∗ = 1.73 × C11−0.38, R2 = 0.96). Similarly, rheometry-derived G∗ at 1 Hz, increasing from 0.66 ± 1.03 kPa (1% strain) to 1.84 ± 1.65 kPa (30% strain, RM one-way ANOVA, P < 0.001), and the frequency dependence of G∗ followed a power-law with the exponent decreasing from 0.13 to 0.06 with increasing preload. MR elastography-derived G∗ was 1.4–3.1 times higher than the extrapolated rheometry-derived G∗ at 60 Hz, but the strain dependence was consistent between rheometry and MR elastography measurements. ConclusionsThis study demonstrates that MR elastography can detect changes in ex vivo bovine liver complex shear modulus due to either uniform or focal preload and therefore can be a useful technique to characterize nonlinear viscoelastic properties of soft tissue, provided that strains applied to the tissue can be quantified. Although MR elastography could reliably characterize the strain dependence of the ex vivo bovine liver, MR elastography overestimated the complex shear modulus of the tissue compared to rheological measurements, particularly at lower preload (<10%). That is likely to be important in clinical hepatic MR elastography diagnosis studies if preload is not carefully considered. A limitation is the absence of overlapping frequency between rheometry and MR elastography for formal validation.

Characterization of mechanical properties of soft tissues using sub-microscale tensile testing and 3D-Printed sample holder

Obtaining the mechanical properties of soft tissues is critical in many medical fields, such as regenerative medicine and surgical simulation training. Although various tissue-characterization methods have been developed, such as AFM, indentation, and elastography, there remain some limitations on their accuracy and validity for measuring small and fragile soft tissues. This paper presents a tensile testing technique to measure the mechanical properties of soft tissues directly and accurately. Tensile testing was chosen as the primary method because of its simple procedure and ability to derive mechanical properties without requiring many assumptions or complicated models. However, tensile testing on soft tissues presents challenges related to gripping the tissue sample without affecting its inherent properties, applying minuscule forces to the sample, and measuring the cross-section area and strain of the sample. To solve these issues, this study presents a sub-micro scale tensile testing system that uses a flexure mechanism and a novel 3D-printed sample holder for gripping the tissue samples. The system also measures tested samples' cross-section area and strain using two high-resolution cameras. The system was validated by testing standard materials and used to characterize the elastic modulus, yield stress, and yield strain of lung tissue slices from six different mice. The results from the validation tests showed a less than 2.5% error for elastic modulus values measured using the tensile tester. At the same time, results from the mice lung tissue measurements revealed qualitative findings that closely matched those seen in the literature and displayed low coefficient of variation values, demonstrating the high repeatability of the system.

The impact of thickness heterogeneity on soft tissue biomechanics: a novel measurement technique and a demonstration on heart valve tissue.

The mechanical properties of soft tissues are driven by their complex, heterogeneous composition and structure. Interestingly, studies of soft tissue biomechanics often ignore spatial heterogeneity. In our work, we are therefore interested in exploring the impact of tissue heterogeneity on the mechanical properties of soft tissues. Therein, we specifically focus on soft tissue heterogeneity arising from spatially varying thickness. To this end, our first goal is to develop a non-destructive measurement technique that has a high spatial resolution, provides continuous thickness maps, and is fast. Our secondary goal is to demonstrate that including spatial variation in thickness is important to the accuracy of biomechanical analyses. To this end, we use mitral valve leaflet tissue as our model system. To attain our first goal, we identify a soft tissue-specific contrast protocol that enables thickness measurements using a Keyence profilometer. We also show that this protocol does not affect our tissues' mechanical properties. To attain our second goal, we conduct virtual biaxial, bending, and buckling tests on our model tissue both ignoring and considering spatial variation in thickness. Thereby, we show that the assumption of average, homogeneous thickness distributions significantly alters the results of biomechanical analyses when compared to including true, spatially varying thickness distributions. In conclusion, our work provides a novel measurement technique that can capture continuous thickness maps non-invasively, at high resolution, and in a short time. Our work also demonstrates the importance of including heterogeneous thickness in biomechanical analyses of soft tissues.