Torsional wave elastography to assess the mechanical properties of the cornea

Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in platelike media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment ( NH 4OH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.Ministerio de Educacion, Cultura y Deporte Grant DPI2017-83859-R DPI2014-51870-R UNGR15-CE-3664 EQC2018-004508-PSpanish Government DTS15/00093 PI16/00339Instituto de Salud Carlos III y Fondos FederJunta de Andalucia PI-0107-2017 PIN-0030-2017 IE2017-5537MCIN/AEI - European Social Fund "Investing in your future" PRE2018-086085Consejeria de economia, conocimiento, empresas y universidad SOMM17/6109/UGR B-TEP-026- IE2017-5537 P18-RT-1653European Commission SOMM17/6109/UGR B-TEP-026- IE2017-5537 P18-RT-165

The emergence of optical elastography in biomedicine

The authors thank their colleagues past and present who have contributed to the evolution of optical elastography; in particular, S. Adie, W. Allen, L. Chin, B. Quirk, A. Curatolo, S. Es'hagian, K. Kennedy, R. Kirk, R. McLaughlin and P. Munro. This work has been supported in part by the Australian Research Council, the National Health and Medical Research Council, the National Breast Cancer Foundation, and the Western Australian Department of Health. P.W. thanks the Schrader Trust for a studentship.Optical elastography, the use of optics to characterize and map the mechanical properties of biological tissue, involves measuring the deformation of tissue in response to a load. Such measurements may be used to form an image of a mechanical property, often elastic modulus, with the resulting mechanical contrast complementary to the more familiar optical contrast. Optical elastography is experiencing new impetus in response to developments in the closely related fields of cell mechanics and medical imaging, aided by advances in photonics technology, and through probing the microscale between that of cells and whole tissues. Two techniques-optical coherence elastography and Brillouin microscopy-have recently shown particular promise for medical applications, such as in ophthalmology and oncology, and as new techniques in cell mechanics.PostprintPeer reviewe

A biomechanical analysis of shear wave elastography in pediatric heart models

Early detection of cardiac disease in children is essential to optimize treatment and follow-up, but also to reduce its associated mortality and morbidity. Various cardiac imaging modalities are available for the cardiologist, mainly providing information on tissue morphology and structure with high temporal and/or spatial resolution. However, none of these imaging methods is able to directly measure stresses or intrinsic mechanical properties of the heart, which are potential key diagnostic markers to distinguish between normal and abnormal physiology. This thesis investigates the potential of a relatively new ultrasound-based technique, called shear wave elastography (SWE), to non-invasively measure myocardial stiffness. The technique generates an internal perturbation inside the tissue of interest, and consequently measures the propagation of the acoustically excited shear wave, of which the propagation speed is directly related to tissue stiffness. This allows SWE to identify regions with higher stiffness, which is associated with pathology. SWE has shown to be successful in detecting tumors in breast tissue and fibrosis in liver tissue, however application of SWE to the heart is more challenging due to the complex mechanical and structural properties of the heart. This thesis provides insights into the acoustically excited shear wave physics in the myocardium by using computer simulations in combination with experiments. Furthermore, these models also allow to assess the performance of currently used SWE-based material characterization algorithms

Nonlinear fourth‐order elastic characterization of the cornea using torsional wave elastography

Measuring the mechanical nonlinear properties of the cornea remains challenging due to the lack of consensus in the methodology and in the models that effectively predict its behaviour. This study proposed developing a procedure to reconstruct nonlinear fourth-order elastic properties of the cornea based on a mathematical model derived from the theory of Hamilton et al. and using the torsional wave elastography (TWE) technique. In order to validate its diagnostic capability of simulated pathological conditions, two different groups were studied, non-treated cornea samples (n=7), and ammonium hydroxide (NH4OH) treated samples (n=7). All the samples were measured in-plane by a torsional wave device by increasing IOP from 5 to 25 mmHg with 5 mmHg steps. The results show a nonlinear variation of the shear wave speed with the IOP, with higher values for higher IOPs. Moreover, the shear wave speed values of the control group were higher than those of the treated group. The study also revealed significant differences between the control and treated groups for the Lamé parameter ���� (25.9–6.52 kPa), third-order elastic constant A (215.09–44.85 kPa), and fourth-order elastic constant D (523.5–129.63 kPa), with p-values of 0.010, 0.024, and 0.032, respectively. These findings demonstrate that the proposed procedure can distinguish between healthy and damaged corneas, making it a promising technique for detecting diseases associated with IOP alteration, such as corneal burns, glaucoma, or ocular hypertension

Elastographie et retournement temporel des ondes de cisaillement (application à l'imagerie des solides mous)

L'interaction onde-matière a toujours été un sujet d'étude en Physique, c est le cas de la propagation des ondes élastiques dans le corps humain qu a conduit à plusieurs modalités d'imagerie. En particulier, les techniques d'elastographie reposent sur l'utilisation des ondes de cisaillement pour obtenir une image élastique des tissus mous. Dans ce contexte, cette thèse présente une étude des différentes techniques d'élastographie, en prêtant particulier attention aux aspects plus fondamentaux comme à ces potentielles applications.Tout d'abord, cette thèse montre que l'élastographie impulsionnelle unidimensionnelle (1D) peut être utilisée pour évaluer l'élasticité des couches de tissue d'épaisseur inférieure à la longueur d'onde utilisée. A cet effet, des simulations et des expériences ont été réalisées avec différents fantômes formés par une couche mince immergée dans un milieu d'élasticité différente. La concordance entre expériences et simulations, ainsi que le valeur de l'élasticité obtenue par élastographie 1D et le valeur de l'élasticité intrinsèque de la couche permettent de valider cette technique. Au même temps ces résultats ont été comparés avec ceux obtenus par la technique de Supersonic Shear Imaging (SSI), où l'onde est guidée le long de la plaque. On ajustant la courbe de dispersion expérimentale obtenue par SSI avec un modèle de Lamb, l'élasticité intrinsèque de chaque plaque est estimée. Les résultats obtenus par élastographie 1D et SSI montrent un bon accord entre eux. Le principal avantage de l'élastographie 1D est qu il n'est pas nécessaire d'utiliser un modèle pour estimer l'élasticité de la plaque. Deuxièmement, deux nouvelles modalités d'imagerie quantitative pour l'extraction de élasticité des tissus mou à partir d'un champ élastique complexe sont approfondies: l'Elastographie par Retournement Temporel et le filtre inverse passif. Le but de ces deux techniques est d'estimer localement l'élasticité des tissus, par la mesure de la taille de la tâche focale dans une expérience virtuelle de retournement temporel avec des ondes de cisaillement. A partir de l'étude du processus de retournement temporel dans les solides mous, la faisabilité de ces deux techniques est démontrée in vitro dans des échantillons "bi-couche" et in vivo dans le foie et les muscles, en utilisant le bruit physiologique naturel crée par l'activité cardiaque et musculaire. L'efficacité de l'élastographie par retournement temporel diminue dans le cas d'un champ diffus non isotrope. L'emploie du filtre inverse adaptée à une configuration de source de bruit, permet de rétablir l'isotropie du champ et d'améliorer la résolution pour la détection de petites inclusions. Le filtre inverse passif permet, de surcroît, de contrôler la fréquence qui domine le champ de retournement temporel. Ceci est exploité, dans la dernière partie du manuscrit, pour mener la première expérience de spectroscopie passive en volume. Deux situations sont envisagées: la dispersion due à la propagation d'ondes guidées dans des plaques minces et la dispersion des ondes due à la viscosité.The interaction between wave and matter has long been studied in Physics. In particular, regarding medical applications, wave propagation through the human body resulted in several imaging modalities, each of which uses a specific type of wave linked to a given physical property. The elasticity of soft biological tissues is directly linked to its shear wave speed. Thus, in Elastography, shear waves are tracked for non-invasive assessment of the mechanical properties of soft tissues. In this context, this thesis proposes a study of different elastography techniques from a basic point of view, as well as from its potential applications. Firstly, in this manuscript, the use of 1D transient elastography for the quantitative elasticity assessment of thin layered soft tissues is proposed. Experiments on three phantoms with different elasticities and plate thicknesses were performed. Experimental shear wave speed estimations inside the plate were obtained and validated with finite difference simulation. In addition, the Supersonic Shear Imaging (SSI) technique was performed. For the SSI technique, the propagating wave inside the plate is guided as a Lamb wave. Experimental SSI dispersion curves were fitted using a generalized Lamb model to retrieve the plate bulk shear wave speed. Finally both techniques resulted in similar shear wave speed estimations. The main advantage of 1D transient elastography is that the bulk shear wave speed can be directly retrieved from a time of flight measurement without requiring a dispersion model. Secondly, throughout this thesis, two novel quantitative imaging modalities for extracting the soft tissue's elasticity from a complex reverberated diffuse elastic field are deepen: Time Reversal Elastography (TRE) and the passive inverse filter. The goal of both techniques is to locally estimate the tissue's elasticity, by measuring the focal spot size in a virtual time reversal experiment involving shear waves. By studying the Physics of a time reversal process in soft solids, the feasibility of both techniques as a quantitative imaging techniques is demonstrated in vitro in bi-layer phantoms and in vivo in the liver-belly muscle, by using the physiological noise due to heartbeats and muscular activity. The efficiency of TRE decreases in the presence of a non-isotropic diffuse field. The use of the inverse filter adapted to a passive source configuration, restores the isotropy of the field. As a consequence, the resolution of the elasticity images is improved, leading to a better detection of small inclusions. In addition, the passive inverse filter allows to control the frequency dominating the time reversed field. This is exploited in the last part of the manuscript to conduct the first passive wave spectroscopy experiment in the volume of a soft solid. Two situations are considered: dispersion due to guided wave propagation in thin plates and wave dispersion due to viscosity effects.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Soft tissue viscoelastic properties: measurements, models and interpretation

The quantification of mechanical properties of soft tissues has been of great interest for more than two decades because they have the potential of being used as biomarkers for disease diagnosis. Indentation techniques, the most recognized techniques for characterizing mechanical properties, are widely used for basic science investigations in research labs. The use of elastography techniques coupled with imaging technologies has been growing rapidly in recent years, which is promising for clinical applications. Each technique produces different mechanical behaviors due to the interaction of the stimuli and the structure of the tissue. An appropriate model will parameterize these behaviors to reflect the corresponding tissue microscopic features with high fidelity. The objective of this thesis is to identify combinations of techniques and models that will yield mechanical parameters with diagnostic interpretations about tissue microenvironment. Three techniques for characterizing tissue viscoelastic properties were developed and validated, each offers strengths in a large variety of applications. Indentation based techniques measure low-frequency force-displacement curves under different loading profiles. Ultrasound-based techniques and optical based techniques measure the dispersion behaviors of the propagating wave velocities at mid-to-high frequency ranges. When a material is linear, isotropic, and contains only elastic components, the “intrinsic” elastic modulus of the material can be obtained independently of the technique used when corrections are properly made to eliminate the bias from boundary effects. If the material includes time-dependent components, models must be included in the analysis to provide parametric estimates. Classical models for viscoelastic solids such as the Kelvin-Voigt model do not fully represent mechanical measurements in tissues because they are not material continua. Tissue properties are determined in part by fluid movement in the open- and closed-cell compartments found within a viscoelastic collagen matrix that is actively maintained by the embedded cells to meet programmed needs. These biphasic (solid/fluid) media exhibit multifaceted deformation responses that are particularly difficult to model using a concise feature set. The Kelvin-Voigt fractional derivative (KVFD) model introduced in this study represents the measurement data of a broad range in both time and frequency domain with a small number of parameters, and it yields stable estimates for many types of phantoms and tissues. It is superior to the integer derivative models for the materials and techniques we used in this study. Moreover, the KVFD model provides a three-dimensional feature space of mechanical properties that properly characterizes the composition and structure of a material. This was validated through measurements on gelatin-cream emulsion samples exhibiting viscoelastic behavior, as well as ex vivo liver tissue samples. For the elastic property, KVFD parameter E_0 mainly represents the elasticity of the solid matrix and is approximately equal to the shear modulus no matter which technique is used. For the viscous property, when combined with different measurement techniques, KVFD model parameter α and τ represent different tissue components. The combination of these techniques and the KVFD model have the potential to be able to distinguish between healthy and pathological tissues described by the histological features

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography

Collagen crosslinking of the cornea (CXL) is commonly employed to prevent or treat keratoconus. Although the change of corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic Optical Coherence Elastography (OCE) by tracking mechanical wave propagation, the depth dependence of this change is still unclear if the cornea is not crosslinked through the whole depth. Here we propose to combine phase-decorrelation measurement applied to OCT structural images and acoustic micro-tapping (A$\mu$T) OCE to explore possible depth reconstruction of stiffness within crosslinked corneas in an ex vivo human cornea sample. The analysis of experimental OCT images is used to define the penetration depth of CXL into the cornea, which varies from $\sim$100$\mu m$ in the periphery to $\sim$150$\mu m$ in the central area and exhibits a sharp transition between areas. This information was used in a two-layer analytical model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reconstructed from OCE measurements reflect the effective mechanical stiffness of the entire cornea to properly quantify surgical outcome.Comment: Main: 10 Pages, 6 Figures Supplemental: 12 Pages, 3 Figure

Ultrasound for Material Characterization and Processing

Ultrasonic waves are nowadays used for multiple purposes including both low-intensity/high frequency and high-intensity/low-frequency ultrasound. Low-intensity ultrasound transmits energy through the medium in order to obtain information about the medium or to convey information through the medium. It is successfully used in non-destructive inspection, ultrasonic dynamic analysis, ultrasonic rheology, ultrasonic spectroscopy of materials, process monitoring, applications in civil engineering, aerospace and geological materials and structures, and in the characterization of biological media. Nowadays, it is an essential tool for assessing metals, plastics, aerospace composites, wood, concrete, and cement. High-intensity ultrasound deliberately affects the propagation medium through the high local temperatures and pressures generated. It is used in industrial processes such as welding, cleaning, emulsification, atomization, etc.; chemical reactions and reactor induced by ultrasonic waves; synthesis of organic and inorganic materials; microstructural effects; heat generation; accelerated material characterization by ultrasonic fatigue testing; food processing; and environmental protection. This book collects eleven papers, one review, and ten research papers with the aim to present recent advances in ultrasonic wave propagation applied for the characterization or the processing of materials. Both fundamental science and applications of ultrasound in the field of material characterization and material processing have been gathered