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.

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'.

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%.

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.

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.

Toward a Predictive Assessment of Stab-Penetration Forces.

Collaborative research between the disciplines of forensic pathology and biomechanics was undertaken to investigate the hyperelastic properties of human skin, to determine the force required for sharp instrument penetration of skin, and to develop a finite element model, which reflects the mechanisms of sharp instrument penetration. These studies have led to the development of a "stab metric," based on simulations, to describe the force magnitudes in stabbing incidents. Such a metric should, in time, replace the crudely quantitative descriptors of stabbing forces currently used by forensic pathologists.

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.

Proper formulation of viscous dissipation for nonlinear waves in solids.

To model nonlinear viscous dissipative motions in solids, acoustical physicists usually add terms linear in E, the material time derivative of the Lagrangian strain tensor E, to the elastic stress tensor σ derived from the expansion to the third (sometimes fourth) order of the strain energy density E=E(tr E,tr E(2),tr E(3)). Here it is shown that this practice, which has been widely used in the past three decades or so, is physically wrong for at least two reasons and that it should be corrected. One reason is that the elastic stress tensor σ is not symmetric while E is symmetric, so that motions for which σ+σ(T)≠0 will give rise to elastic stresses that have no viscous pendant. Another reason is that E is frame-invariant, while σ is not, so that an observer transformation would alter the elastic part of the total stress differently than it would alter the dissipative part, thereby violating the fundamental principle of material frame indifference. These problems can have serious consequences for nonlinear shear wave propagation in soft solids as seen here with an example of a kink in almost incompressible soft solids.

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.

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.

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.

Uniform transmural strain in pre-stressed arteries occurs at physiological pressure.

Residual deformation (strain) exists in arterial vessels, and has been previously proposed to induce homogeneous transmural strain distribution. In this work, we present analytical formulations that predict the existence of a finite internal (homeostatic) pressure for which the transmural deformation is homogenous, and the corresponding stress field. We provide evidence on the physical existence of homeostatic pressure when the artery is modeled as an incompressible tube with orthotropic constitutive strain-energy function. Based on experimental data of rabbit carotid arteries and porcine coronary arteries, the model predicts a homeostatic mean pressure of ~90 mmHg and 70-120 mmHg, respectively. The predictions are well within the physiological pressure range. Some consequences of this strain homogeneity in the physiological pressure range are explored under the proposed assumptions.

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.

On the third- and fourth-order constants of incompressible isotropic elasticity.

Consider the constitutive law for an isotropic elastic solid with the strain-energy function expanded up to the fourth order in the strain and the stress up to the third order in the strain. The stress-strain relation can then be inverted to give the strain in terms of the stress with a view to considering the incompressible limit. For this purpose, use of the logarithmic strain tensor is of particular value. It enables the limiting values of all nine fourth-order elastic constants in the incompressible limit to be evaluated precisely and rigorously. In particular, it is explained why the three constants of fourth-order incompressible elasticity µ, A, and D are of the same order of magnitude. Several examples of application of the results follow, including determination of the acoustoelastic coefficients in incompressible solids and the limiting values of the coefficients of nonlinearity for elastic wave propagation.

Third- and fourth-order elasticities of biological soft tissues.

In the theory of weakly nonlinear elasticity, Hamilton et al. [J. Acoust. Soc. Am. 116, 41-44 (2004)] identified W=muI(2)+(A/3)I(3)+DI(2) (2) as the fourth-order expansion of the strain-energy density for incompressible isotropic solids. Subsequently, much effort focused on theoretical and experimental developments linked to this expression in order to inform the modeling of gels and soft biological tissues. However, while many soft tissues can be treated as incompressible, they are not in general isotropic, and their anisotropy is associated with the presence of oriented collagen fiber bundles. Here the expansion of W is carried up to fourth order in the case where there exists one family of parallel fibers in the tissue. The results are then applied to acoustoelasticity, with a view to determining the second- and third-order nonlinear constants by employing small-amplitude transverse waves propagating in a deformed soft tissue.

Third- and fourth-order constants of incompressible soft solids and the acousto-elastic effect.

Acousto-elasticity is concerned with the propagation of small-amplitude waves in deformed solids. Results previously established for the incremental elastodynamics of exact non-linear elasticity are useful for the determination of third- and fourth-order elastic constants, especially in the case of incompressible isotropic soft solids, where the expressions are particularly simple. Specifically, it is simply a matter of expanding the expression for ρv(2), where ρ is the mass density and v the wave speed, in terms of the elongation e of a block subject to a uniaxial tension. The analysis shows that in the resulting expression: ρv(2) = a+be+ce(2), say, a depends linearly on µ; b on µ and A; and c on µ, A, and D, the respective second-, third, and fourth-order constants of incompressible elasticity, for bulk shear waves and for surface waves.

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).