A Gaussian process approach for rapid evaluation of skin tension.

Skin tension plays a pivotal role in clinical settings, it affects scarring, wound healing and skin necrosis. Despite its importance, there is no widely accepted method for assessing in vivo skin tension or its natural pre-stretch. This study aims to utilise modern machine learning (ML) methods to develop a model that uses non-invasive measurements of surface wave speed to predict clinically useful skin properties such as stress and natural pre-stretch. A large dataset consisting of simulated wave propagation experiments was created using a simplified two-dimensional finite element (FE) model. Using this dataset, a sensitivity analysis was performed, highlighting the effect of the material parameters and material model on the Rayleigh and supersonic shear wave speeds. Then, a Gaussian process regression model was trained to solve the ill-posed inverse problem of predicting stress and pre-stretch of skin using measurements of surface wave speed. This model had good predictive performance (R2 = 0.9570) and it was possible to interpolate simplified parametric equations to calculate the stress and pre-stretch. To demonstrate that wave speed measurements could be obtained cheaply and easily, a simple experiment was devised to obtain wave speed measurements from synthetic skin at different values of pre-stretch. These experimental wave speeds agree well with the FE simulations, and a model trained solely on the FE data provided accurate predictions of synthetic skin stiffness. Both the simulated and experimental results provide further evidence that elastic wave measurements coupled with ML models are a viable non-invasive method to determine in vivo skin tension. STATEMENT OF SIGNIFICANCE: To prevent unfavourable patient outcomes from reconstructive surgery, it is necessary to determine relevant subject-specific skin properties. For example, during a skin graft, it is necessary to estimate the pre-stretch of the skin to account for shrinkage upon excision. Existing methods are invasive or rely on the experience of the clinician. Our work aims to present an innovative framework to non-invasively determine in vivo material properties using the speed of a surface wave travelling through the skin. Our findings have implications for the planning of surgical procedures and provides further motivation for the use of elastic wave measurements to determine in vivo material properties.

An atlas of the heterogeneous viscoelastic brain with local power-law attenuation synthesised using Prony-series.

This review addresses the acute need to acknowledge the mechanical heterogeneity of brain matter and to accurately calibrate its local viscoelastic material properties accordingly. Specifically, it is important to compile the existing and disparate literature on attenuation power-laws and dispersion to make progress in wave physics of brain matter, a field of research that has the potential to explain the mechanisms at play in diffuse axonal injury and mild traumatic brain injury in general. Currently, viscous effects in the brain are modelled using Prony-series, i.e., a sum of decaying exponentials at different relaxation times. Here we collect and synthesise the Prony-series coefficients appearing in the literature for twelve regions: brainstem, basal ganglia, cerebellum, corona radiata, corpus callosum, cortex, dentate gyrus, hippocampus, thalamus, grey matter, white matter, homogeneous brain, and for eight different mammals: pig, rat, human, mouse, cow, sheep, monkey and dog. Using this data, we compute the fractional-exponent attenuation power-laws for different tissues of the brain, the corresponding dispersion laws resulting from causality, and the averaged Prony-series coefficients. STATEMENT OF SIGNIFICANCE: Traumatic brain injuries are considered a silent epidemic and finite element methods (FEMs) are used in modelling brain deformation, requiring access to viscoelastic properties of brain. To the best of our knowledge, this work presents 1) the first multi-frequency viscoelastic atlas of the heterogeneous brain, 2) the first review focusing on viscoelastic modelling in both FEMs and experimental works, 3) the first attempt to conglomerate the disparate existing literature on the viscoelastic modelling of the brain and 4) the largest collection of viscoelastic parameters for the brain (212 different Prony-series spanning 12 different tissues and 8 different animal surrogates). Furthermore, this work presents the first brain atlas of attenuation power-laws essential for modelling shear waves in brain.

Analysis of In Vivo Skin Anisotropy Using Elastic Wave Measurements and Bayesian Modelling.

In vivo skin exhibits viscoelastic, hyper-elastic and non-linear characteristics. It is under a constant state of non-equibiaxial tension in its natural configuration and is reinforced with oriented collagen fibers, which gives rise to anisotropic behaviour. Understanding the complex mechanical behaviour of skin has relevance across many sectors including pharmaceuticals, cosmetics and surgery. However, there is a dearth of quality data characterizing the anisotropy of human skin in vivo. The data available in the literature is usually confined to limited population groups and/or limited angular resolution. Here, we used the speed of elastic waves travelling through the skin to obtain measurements from 78 volunteers ranging in age from 3 to 93 years old. Using a Bayesian framework allowed us to analyse the effect that age, gender and level of skin tension have on the skin anisotropy and stiffness. First, we propose a new measurement of anisotropy based on the eccentricity of angular data and conclude that it is a more robust measurement when compared to the classic "anisotropic ratio". Our analysis then concluded that in vivo skin anisotropy increases logarithmically with age, while the skin stiffness increases linearly along the direction of Langer Lines. We also concluded that the gender does not significantly affect the level of skin anisotropy, but it does affect the overall stiffness, with males having stiffer skin on average. Finally, we found that the level of skin tension significantly affects both the anisotropy and stiffness measurements employed here. This indicates that elastic wave measurements may have promising applications in the determination of in vivo skin tension. In contrast to earlier studies, these results represent a comprehensive assessment of the variation of skin anisotropy with age and gender using a sizeable dataset and robust modern statistical analysis. This data has implications for the planning of surgical procedures and questions the adoption of universal cosmetic surgery practices for very young or elderly patients.

Noninvasive measurement of local stress inside soft materials with programmed shear waves.

Mechanical stresses across different length scales play a fundamental role in understanding biological systems' functions and engineering soft machines and devices. However, it is challenging to noninvasively probe local mechanical stresses in situ, particularly when the mechanical properties are unknown. We propose an acoustoelastic imaging-based method to infer the local stresses in soft materials by measuring the speeds of shear waves induced by custom-programmed acoustic radiation force. Using an ultrasound transducer to excite and track the shear waves remotely, we demonstrate the application of the method by imaging uniaxial and bending stresses in an isotropic hydrogel and the passive uniaxial stress in a skeletal muscle. These measurements were all done without the knowledge of the constitutive parameters of the materials. The experiments indicate that our method will find broad applications, ranging from health monitoring of soft structures and machines to diagnosing diseases that alter stresses in soft tissues.

Modelling brain tissue elasticity with the Ogden model and an alternative family of constitutive models†.

The Ogden model is often considered as a standard model in the literature for application to the deformation of brain tissue. Here, we show that, in some of those applications, the use of the Ogden model leads to the non-convexity of the strain-energy function and mis-prediction of the correct concavity of the experimental stress-stretch curves over a range of the deformation domain. By contrast, we propose a family of models which provides a favourable fit to the considered datasets while remaining free from the highlighted shortcomings of the Ogden model. While, as we discuss, those shortcomings might be due to the artefacts of the testing protocols, the proposed family of models proves impervious to such artefacts. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.

The Ogden model of rubber mechanics: 50 years of impact on nonlinear elasticity.

We place the Ogden model of rubber elasticity, published in Proceedings of the Royal Society 50 years ago, in the wider context of the theory of nonlinear elasticity. We then follow with a short interview of Ray Ogden FRS and introduce the papers collected for this Theme Issue. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.

Proton Resonance Frequency Shift Thermometry: A Review of Modern Clinical Practices.

Magnetic resonance imaging (MRI) has become a popular modality in guiding minimally invasive thermal therapies, due to its advanced, nonionizing, imaging capabilities and its ability to record changes in temperature. A variety of MR thermometry techniques have been developed over the years, and proton resonance frequency (PRF) shift thermometry is the current clinical gold standard to treat a variety of cancers. It is used extensively to guide hyperthermic thermal ablation techniques such as high-intensity focused ultrasound (HIFU) and laser-induced thermal therapy (LITT). Essential attributes of PRF shift thermometry include excellent linearity with temperature, good sensitivity, and independence from tissue type. This noninvasive temperature mapping method gives accurate quantitative measures of the temperature evolution inside biological tissues. In this review, the current status and new developments in the fields of MR-guided HIFU and LITT are presented with an emphasis on breast, prostate, bone, uterine, and brain treatments. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Non-destructive mapping of stress and strain in soft thin films through sound waves.

Measuring the in-plane mechanical stress in a taut membrane is challenging, especially if its material parameters are unknown or altered by the stress. Yet being able to measure the stress is of fundamental interest to basic research and practical applications that use soft membranes, from engineering to tissues. Here we present a robust non-destructive technique to measure directly in-situ stress and strain in soft thin films without the need to calibrate material parameters. Our method relies on measuring the speed of elastic waves propagating in the film. Using optical coherence tomography, we verify our method experimentally for a stretched rubber membrane, a piece of cling film (about 10 µm thick), and the leather skin of a traditional Irish frame drum. We find that our stress predictions are highly accurate and anticipate that our technique could be useful in applications ranging from soft matter devices to biomaterial engineering and medical diagnosis.

Acousto-elasticity of transversely isotropic incompressible soft tissues: characterization of skeletal striated muscle.

Using shear wave elastography, we measure the changes in the wave speed with the stress produced by a striated muscle during isometric voluntary contraction. To isolate the behaviour of an individual muscle from complementary or antagonistic actions of adjacent muscles, we select theflexor digiti minimimuscle, whose sole function is to extend the little finger. To link the wave speed to the stiffness, we develop an acousto-elastic theory for shear waves in homogeneous, transversely isotropic, incompressible solids subject to an uniaxial stress. We then provide measurements of the apparent shear elastic modulus along, and transversely to, the fibre axis for six healthy human volunteers of different age and sex. The results display a great variety across the six subjects. We find that the slope of the apparent shear elastic modulus along the fibre direction changes inversely to the maximum voluntary contraction (MVC) produced by the volunteer. We propose an interpretation of our results by introducing the S (slow) or F (fast) nature of the fibres, which harden the muscle differently and accordingly, produce different MVCs. A natural follow-up on this study is to apply the method to patients with musculoskeletal disorders or neurodegenerative diseases.

An ultrasonic method to measure stress without calibration: The angled shear wave method.

Measuring stress levels in loaded structures is crucial to assess and monitor structure health and to predict the length of remaining structural life. Many ultrasonic methods are able to accurately predict in-plane stresses inside a controlled laboratory environment but struggle to be robust outside, in a real-world setting. That is because these methods rely either on knowing beforehand the material constants (which are difficult to acquire) or require significant calibration for each specimen. This paper presents an ultrasonic method to evaluate the in-plane stress in situ directly, without knowing any material constants. The method is simple in principle, as it only requires measuring the speed of two angled shear waves. It is based on a formula that is exact for incompressible solids, such as soft gels or tissues, and is approximately true for compressible "hard" solids, such as steel and other metals. The formula is validated by finite element simulations, showing that it displays excellent accuracy, with a small error on the order of 1%.

The effect of an exterior electric field on the instability of dielectric plates.

We investigate the theoretical nonlinear response, Hessian stability, and possible wrinkling behaviour of a voltage-activated dielectric plate immersed in a tank filled with silicone oil. Fixed rigid electrodes are placed on the top and bottom of the tank, and an electric field is generated by a potential difference between the electrodes. We solve the associated incremental boundary value problem of superimposed, inhomogeneous small-amplitude wrinkles, signalling the onset of instability. We decouple the resulting bifurcation equation into symmetric and antisymmetric modes. For a neo-Hookean dielectric plate, we show that a potential difference between the electrodes can induce a thinning of the plate and thus an increase of its planar area, similar to the scenarios encountered when there is no silicone oil. However, we also find that, depending on the material and geometric parameters, an increasing applied voltage can also lead to a thickening of the plate, and thus a shrinking of its area. In that scenario, Hessian instability and wrinkling bifurcation may then occur spontaneously once some critical voltages are reached.

Mechanics of human brain organoids.

Organoids are prototypes of human organs derived from cultured human stem cells. They provide a reliable and accurate experimental model to study the physical mechanisms underlying the early developmental stages of human organs and, in particular, the early morphogenesis of the cortex. Here we propose a mathematical model to elucidate the role played by two mechanisms which have been experimentally proven to be crucial in shaping human brain organoids: the contraction of the inner core of the organoid and the microstructural remodeling of its outer cortex. Our results show that both mechanisms are crucial for the final shape of the organoid and that perturbing those mechanisms can lead to pathological morphologies which are reminiscent of those associated with lissencephaly (smooth brain).

Prescribing patterns in growing tubular soft matter by initial residual stress.

Initial residual stress is omnipresent in biological tissues and soft matter, and can affect growth-induced pattern selection significantly. Here we demonstrate this effect experimentally by letting soft tubes grow in the presence or absence of initial residual stress and by observing different growth pattern evolutions. These experiments motivate us to model the mechanisms at play when a growing bilayer tubular organ spontaneously displays buckling patterns on its inner surface. We demonstrate that not only differential growth, geometry and elasticity, but also initial residual stress distribution, exert a notable influence on these pattern phenomena. Prescribing an initial residual stress distribution offers an alternative or a more effective way to implement pattern selection for growable bio-tissues or soft matter. The results also show promise for the design of 4D bio-mimic printing protocols or for controlling hydrogel actuators.

Generalization of the Zabolotskaya equation to all incompressible isotropic elastic solids.

We study elastic shear waves of small but finite amplitude, composed of an anti-plane shear motion and a general in-plane motion. We use a multiple scales expansion to derive an asymptotic system of coupled nonlinear equations describing their propagation in all isotropic incompressible nonlinear elastic solids, generalizing the scalar Zabolotskaya equation of compressible nonlinear elasticity. We show that for a general isotropic incompressible solid, the coupling between anti-plane and in-plane motions cannot be undone and thus conclude that linear polarization is impossible for general nonlinear two-dimensional shear waves. We then use the equations to study the evolution of a nonlinear Gaussian beam in a soft solid: we show that a pure (linearly polarized) shear beam source generates only odd harmonics, but that introducing a slight in-plane noise in the source signal leads to a second harmonic, of the same magnitude as the fifth harmonic, a phenomenon recently observed experimentally. Finally, we present examples of some special shear motions with linear polarization.

Multi-sector approximation method for arteries: the residual stresses of circumferential rings with non-trivial openings.

The opening angle method is a popular choice in biomechanics to estimate residual stresses in arteries. Experimentally, it means that an artery is cut into rings; then the rings are cut axially or radially allowing them to open into sectors; finally, the corresponding opening angles are measured to give residual stress levels by solving an inverse problem. However, for many tissues, for example in pathological tissues, the ring does not open according to the theory into a neat single circular sector, but rather creates an asymmetric geometry, often with abruptly changing curvature(s). This phenomenon may be due to a number of reasons including variation in thickness, microstructure, mechanical properties, etc. As a result, these samples are often eliminated from studies relying on the opening angle method, which limits progress in understanding and evaluating residual stresses in real arteries. With this work, we propose an effective approach to deal with these non-trivial openings of rings. First, we digitize pictures of opened rings to split them into multiple, connected circular sectors. Then we measure the corresponding opening angles for each sub-sector. Subsequently, we can determine the residual stresses for individual sectors in a closed-ring configuration and, thus, approximate the circumferential residual bending effects.

Influence of Initial Residual Stress on Growth and Pattern Creation for a Layered Aorta.

Residual stress is ubiquitous and indispensable in most biological and artificial materials, where it sustains and optimizes many biological and functional mechanisms. The theory of volume growth, starting from a stress-free initial state, is widely used to explain the creation and evolution of growth-induced residual stress and the resulting changes in shape, and to model how growing bio-tissues such as arteries and solid tumors develop a strategy of pattern creation according to geometrical and material parameters. This modelling provides promising avenues for designing and directing some appropriate morphology of a given tissue or organ and achieve some targeted biomedical function. In this paper, we rely on a modified, augmented theory to reveal how we can obtain growth-induced residual stress and pattern evolution of a layered artery by starting from an existing, non-zero initial residual stress state. We use experimentally determined residual stress distributions of aged bi-layered human aortas and quantify their influence by a magnitude factor. Our results show that initial residual stress has a more significant impact on residual stress accumulation and the subsequent evolution of patterns than geometry and material parameters. Additionally, we provide an essential explanation for growth-induced patterns driven by differential growth coupled to an initial residual stress. Finally, we show that initial residual stress is a readily available way to control growth-induced pattern creation for tissues and thus may provide a promising inspiration for biomedical engineering.

Poynting effect of brain matter in torsion.

We investigate experimentally and model theoretically the mechanical behaviour of brain matter in torsion. Using a strain-controlled rheometer, we perform torsion tests on fresh porcine brain samples. We quantify the torque and the normal force required to twist a cylindrical sample at constant twist rate. Data fitting gives a mean value for the shear modulus of µ = 900 ± 312 Pa and for the second Mooney-Rivlin parameter of c2 = 297 ± 189 Pa, indicative of extreme softness. Our results show that brain always displays a positive Poynting effect; in other words, it expands in the direction perpendicular to the plane of twisting. We validate the experiments with finite element simulations and show that when a human head experiences a twisting motion in the horizontal plane, the brain can experience large forces in the axial direction.

Head-to-nerve analysis of electromechanical impairments of diffuse axonal injury.

The aim was to investigate mechanical and functional failure of diffuse axonal injury (DAI) in nerve bundles following frontal head impacts, by finite element simulations. Anatomical changes following traumatic brain injury are simulated at the macroscale by using a 3D head model. Frontal head impacts at speeds of 2.5-7.5 m/s induce mild-to-moderate DAI in the white matter of the brain. Investigation of the changes in induced electromechanical responses at the cellular level is carried out in two scaled nerve bundle models, one with myelinated nerve fibres, the other with unmyelinated nerve fibres. DAI occurrence is simulated by using a real-time fully coupled electromechanical framework, which combines a modulated threshold for spiking activation and independent alteration of the electrical properties for each three-layer fibre in the nerve bundle models. The magnitudes of simulated strains in the white matter of the brain model are used to determine the displacement boundary conditions in elongation simulations using the 3D nerve bundle models. At high impact speed, mechanical failure occurs at lower strain values in large unmyelinated bundles than in myelinated bundles or small unmyelinated bundles; signal propagation continues in large myelinated bundles during and after loading, although there is a large shift in baseline voltage during loading; a linear relationship is observed between the generated plastic strain in the nerve bundle models and the impact speed and nominal strains of the head model. The myelin layer protects the fibre from mechanical damage, preserving its functionalities.

Effects of nerve bundle geometry on neurotrauma evaluation.

OBJECTIVE: We confirm that alteration of a neuron structure can induce abnormalities in signal propagation for nervous systems, as observed in brain damage. Here, we investigate the effects of geometrical changes and damage of a neuron structure in 2 scaled nerve bundle models, made of myelinated nerve fibers or unmyelinated nerve fibers. METHODS: We propose a 3D finite element model of nerve bundles, combining a real-time full electromechanical coupling, a modulated threshold for spiking activation, and independent alteration of the electrical properties for each fiber. With the inclusion of plasticity, we then simulate mechanical compression and tension to induce damage at the membrane of a nerve bundle made of 4 fibers. We examine the resulting changes in strain and neural activity by considering in turn the cases of intact and traumatized nerve membranes. RESULTS: Our results show lower strain and lower electrophysiological impairments in unmyelinated fibers than in myelinated fibers, higher deformation levels in larger bundles, and higher electrophysiological impairments in smaller bundles. CONCLUSION: We conclude that the insulation sheath of myelin constricts the membrane deformation and scatters plastic strains within the bundle, that larger bundles deform more than small bundles, and that small fibers tolerate a higher level of elongation before mechanical failure.