Full-field noise-correlation elastography for in-plane mechanical anisotropy imaging.

Elastography contrast imaging has great potential for the detection and characterization of abnormalities in soft biological tissues to help physicians in diagnosis. Transient shear-waves elastography has notably shown promising results for a range of clinical applications. In biological soft tissues such as muscle, high mechanical anisotropy implies different stiffness estimations depending on the direction of the measurement. In this study, we propose the evolution of a noise-correlation elastography approach for in-plane anisotropy mapping. This method is shown to retrieve anisotropy from simulation images before being validated on agarose anisotropic tissue-mimicking phantoms, and the first results on in-vivo biological fibrous tissues are presented.

In plane quantification ofin vivomuscle elastic anisotropy factor by steered ultrasound pushing beams.

Objective.Skeletal muscles are organized into distinct layers and exhibit anisotropic characteristics across various scales. Assessing the arrangement of skeletal muscles may provide valuable biomarkers for diagnosing muscle-related pathologies and evaluating the efficacy of clinical interventions.Approach. In this study, we propose a novel ultrafast ultrasound sequence constituted of steered pushing beams was proposed for ultrasound elastography applications in transverse isotropic muscle. Based on the propagation of the shear wave vertical mode, it is possible to fit the experimental results to retrieve in the same imaging plane, the shear modulus parallel to fibers as well as the elastic anisotropy factor (ratio of Young's moduli times the shear modulus perpendicular to fibers).Main results. The technique was demonstratedin vitroin phantoms andex vivoin fusiform beef muscles. At last, the technique was appliedin vivoon fusiform muscles (biceps brachii) and mono-pennate muscles (gastrocnemius medialis) during stretching and contraction.Significance. This novel sequence provides access to new structural and mechanical biomarkers of muscle tissue, including the elastic anisotropy factor, within the same imaging plane. Additionally, it enables the investigation of multiples parameters during muscle active and passive length changes.

Ultrasonic elastography for the prevention of breast implant rupture: Detection of an increase with stiffness over implantation time.

Breast implants are widely used after breast cancer resection and must be changed regularly to avoid a rupture. To date, there are no quantitative criteria to help this decision. The mechanical evolution of the gels and membranes of the implants is still underinvestigated, although it can lead to early rupture. In this study, 35 breast explants having been implanted in patients for up to 17 years were characterized by ex vivo measurements of their mechanical properties. Using Acoustic Radiation Force Impulse (ARFI) ultrasound elastography, an imaging method for non-destructive mechanical characterization, an increase in the stiffness of the explants has been observed. This increase was correlated with the implantation duration, primarily after 8 years of implantation. With an increase of the shear modulus of up to a factor of nearly 3, the loss of flexibility of the implants is likely to lead to a significant increase of their risk of rupture. A complementary analysis of the gel from the explants by mass spectrometry imaging (MSI) and liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) confirms the presence of metabolites of cholesterol originating from the breast tissues, which most likely crossed the membrane of the implants and most likely degrades the gel. By observing the consequences of the physical-chemical mechanisms at work within patients, this study shows that ultrasound elastography could be used in vivoas a quantitative indicator of the risk of breast implant rupture and help diagnose their replacement.

Unravelling anisotropic nonlinear shear elasticity in muscles: Towards a non-invasive assessment of stress in living organisms.

Acoustoelasticity theory describes propagation of shear waves in uniaxially stressed medium and allows the retrieval of nonlinear elastic coefficients of tissues. In transverse isotropic medium such as muscles the theory leads to 9 different configurations of propagating shear waves (stress axis vs. fibers axis vs. shear wave polarization axis vs. shear wave propagation axis). In this work we propose to use 4 configurations to quantify these nonlinear parameters ex vivo and in vivo. Ex vivo experiments combining ultrasound shear wave elastography and mechanical testing were conducted on iliopsoas pig muscles to quantify three third-order nonlinear coefficients A, H and K that are possibly linked to the architectural structure of muscles. In vivo experiments were performed with human volunteers on biceps brachii during a stretching exercise on an ergometer. A combination of the third order nonlinear elastic parameters was assessed. The knowledge of this nonlinear elastic parameters paves the way to quantify in vivo the local forces produced by muscle during exercise, contraction or movements.

Smart Ultrasound Device for Non-Invasive Real-Time Myocardial Stiffness Quantification of the Human Heart.

Quantitative assessment of myocardial stiffness is crucial to understand and evaluate cardiac biomechanics and function. Despite the recent progresses of ultrasonic shear wave elastography, quantitative evaluation of myocardial stiffness still remains a challenge because of strong elastic anisotropy. In this paper we introduce a smart ultrasound approach for non-invasive real-time quantification of shear wave velocity (SWV) and elastic fractional anisotropy (FA) in locally transverse isotropic elastic medium such as the myocardium. The approach relies on a simultaneous multidirectional evaluation of the SWV without a prior knowledge of the fiber orientation. We demonstrated that it can quantify accurately SWV in the range of 1.5 to 6 m/s in transverse isotropic medium (FA < 0.7) using numerical simulations. Experimental validation was performed on calibrated phantoms and anisotropic ex vivo tissues. A mean absolute error of 0.22 m/s was found when compared to gold standard measurements. Finally, in vivo feasibility of myocardial anisotropic stiffness assessment was evaluated in four healthy volunteers on the antero-septo basal segment and on anterior free wall of the right ventricle (RV) in end-diastole. A mean longitudinal SWV of 1.08 ± 0.20 m/s was measured on the RV wall and 1.74 ± 0.51 m/s on the septal wall with a good intra-volunteer reproducibility (±0.18 m/s). This approach has the potential to become a clinical tool for the quantitative evaluation of myocardial stiffness and diastolic function.

Influence of portal vein occlusion on portal flow and liver elasticity in an animal model.

Hepatic fibrosis causes an increase in liver stiffness, a parameter measured by elastography and widely used as a diagnosis method. The concomitant presence of portal vein thrombosis (PVT) implies a change in hepatic portal inflow that could also affect liver elasticity. The main objective of this study is to determine the extent to which the presence of portal occlusion can affect the mechanical properties of the liver and potentially lead to misdiagnosis of fibrosis and hepatic cirrhosis by elastography. Portal vein occlusion was generated by insertion and inflation of a balloon catheter in the portal vein of four swines. The portal flow parameters peak flow (PF) and peak velocity magnitude (PVM) and liver mechanical properties (shear modulus) were then investigated using 4D-flow MRI and MR elastography, respectively, for progressive obstructions of the portal vein. Experimental results indicate that the reduction of the intrahepatic venous blood flow (PF/PVM decreases of 29.3%/8.5%, 51.0%/32.3% and 83.3%/53.6%, respectively) measured with 50%, 80% and 100% obstruction of the portal vein section results in a decrease of liver stiffness by 0.8% ± 0.1%, 7.7% ± 0.4% and 12.3% ± 0.9%, respectively. While this vascular mechanism does not have sufficient influence on the elasticity of the liver to modify the diagnosis of severe fibrosis or cirrhosis (F4 METAVIR grade), it may be sufficient to attenuate the increase in stiffness due to moderate fibrosis (F2-F3 METAVIR grades) and consequently lead to false-negative diagnoses with elastography in the presence of PVT.

An automatic differentiation-based gradient method for inversion of the shear wave equation in magnetic resonance elastography: specific application in fibrous soft tissues.

Quantitative and accurate measurement of in vivo mechanical properties using dynamic elastography has been the scope of many research efforts over the past two decades. Most of the shear-wave-based inverse approaches for magnetic resonance elastography (MRE) make the assumption of isotropic viscoelasticity. In this paper, we propose a quantitative gradient method for inversion of the shear wave equation in anisotropic media derived from a full waveform description using analytical viscoelastic Green formalism and automatic differentiation. The abilities and performances of the proposed identification method are first evaluated on numerical phantoms calculated in a transversely isotropic medium, and subsequently on experimental MRE data measured on an isotropic hydrogel phantom, on an anisotropic cryogel phantom and on an ex vivo fibrous muscle. The experiments are carried out by coupling circular shear wave profiles generated by acoustic radiation force and MRE acquisition of the wave front. Shear modulus values obtained by our MRE method are compared to those obtained by rheometry in the isotropic hydrogel phantom, and are found to be in good agreement despite non-overlapping frequency ranges. Both the cryogel and the ex vivo muscle are found to be anisotropic. Stiffness values in the longitudinal direction are found to be 1.8 times and 1.9 times higher than those in the transverse direction for the cryogel and the muscle, respectively. The proposed method shows great perspectives and substantial benefits for the in vivo quantitative investigation of complex mechanical properties in fibrous soft tissues.

Ultrafast Harmonic Coherent Compound (UHCC) Imaging for High Frame Rate Echocardiography and Shear-Wave Elastography.

Transthoracic shear-wave elastography (SWE) of the myocardium remains very challenging due to the poor quality of transthoracic ultrafast imaging and the presence of clutter noise, jitter, phase aberration, and ultrasound reverberation. Several approaches, such as diverging-wave coherent compounding or focused harmonic imaging, have been proposed to improve the imaging quality. In this study, we introduce ultrafast harmonic coherent compounding (UHCC), in which pulse-inverted diverging waves are emitted and coherently compounded, and show that such an approach can be used to enhance both SWE and high frame rate (FR) B-mode Imaging. UHCC SWE was first tested in phantoms containing an aberrating layer and was compared against pulse-inversion harmonic imaging and against ultrafast coherent compounding (UCC) imaging at the fundamental frequency. In vivo feasibility of the technique was then evaluated in six healthy volunteers by measuring myocardial stiffness during diastole in transthoracic imaging. We also demonstrated that improvements in imaging quality could be achieved using UHCC B-mode imaging in healthy volunteers. The quality of transthoracic images of the heart was found to be improved with the number of pulse-inverted diverging waves with a reduction of the imaging mean clutter level up to 13.8 dB when compared against UCC at the fundamental frequency. These results demonstrated that UHCC B-mode imaging is promising for imaging deep tissues exposed to aberration sources with a high FR.

Cannabinoid receptor activation in the juvenile rat brain results in rapid biomechanical alterations: Neurovascular mechanism as a putative confounding factor.

We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate the presence of similar effects at the regional level, measures of brain tissue biomechanics are required. However, cannabinoids are known to alter cerebral blood flow (CBF), putatively resulting in presently unexplored changes in cerebral tissue biomechanics. Here we used magnetic resonance elastography (MRE) and flow-sensitive alternating inversion recovery (FAIR) imaging to measure in vivo alterations of mechanical properties and CBF, respectively, in the rat hippocampus, a brain region with a high density of type-1 cannabinoid receptors (CB1R). Systemic injection of the cannabinoid agonist CP55,940 (0.7 mg/kg) induced a significant stiffness decrease of 10.5 ± 1.2% at 15 minutes. FAIR imaging indicated a comparable decrease (11.3 ± 1.9%) in CBF. Both effects were specific to CB1R activation, as shown by pretreatment with the CB1R-specific antagonist AM251. Strikingly, similar rapid parallel changes of brain elasticity and CBF were also observed after systemic treatment with the hypotensive drug nicardipine. Our results reveal important drug-induced parallel changes in CBF and brain mechanical characteristics, and show that blood flow-dependent tissue softening has to be considered as an important putative confounding factor when cerebral viscoelastic changes are investigated.

Modelling the impulse diffraction field of shear waves in transverse isotropic viscoelastic medium.

The generation of shear waves from an ultrasound focused beam has been developed as a major concept for remote palpation using shear wave elastography (SWE). For muscular diagnostic applications, characteristics of the shear wave profile will strongly depend on characteristics of the transducer as well as the orientation of muscular fibers and the tissue viscoelastic properties. The numerical simulation of shear waves generated from a specific probe in an anisotropic viscoelastic medium is a key issue for further developments of SWE in fibrous soft tissues. In this study we propose a complete numerical tool allowing 3D simulation of a shear wave front in anisotropic viscoelastic media. From the description of an ultrasonic transducer, the shear wave source is simulated by using Field's II software and shear wave propagation described by using the Green's formalism. Finally, the comparison between simulations and experiments are successively performed for both shear wave velocity and dispersion profile in a transverse isotropic hydrogel phantom, in vivo forearm muscle and in vivo biceps brachii.

Microvasculature alters the dispersion properties of shear waves--a multi-frequency MR elastography study.

Magnetic Resonance Elastography (MRE) uses macroscopic shear wave propagation to quantify mechanical properties of soft tissues. Micro-obstacles are capable of affecting the macroscopic dispersion properties of shear waves. Since disease or therapy can change the mechanical integrity and organization of vascular structures, MRE should be able to sense these changes if blood vessels represent a source for wave scattering. To verify this, MRE was performed to quantify alteration of the shear wave speed cs due to the presence of vascular outgrowths using an aortic ring model. Eighteen fragments of rat aorta included in a Matrigel matrix (n=6 without outgrowths, n=6 with a radial outgrowth extent of ~600 µm and n=6 with ~850 µm) were imaged using a 7 Tesla MR scanner (Bruker, PharmaScan). High resolution anatomical images were acquired in addition to multi-frequency MRE (ν = 100, 115, 125, 135 and 150 Hz). Average cs was measured within a ring of ~900 µm thickness encompassing the aorta and were normalized to cs0 of the corresponding Matrigel. The frequency dependence was fit to the power law model cs ~ν(y). After scanning, optical microscopy was performed to visualize outgrowths. Results demonstrated that in presence of vascular outgrowths (1) normalized cs significantly increased for the three highest frequencies (Kruskal-Wallis test, P = 0.0002 at 125 Hz and P = 0.002 at 135 Hz and P = 0.003 at 150 Hz) but not for the two lowest (Kruskal-Wallis test, P = 0.63 at 100 Hz and P = 0.87 at 115 Hz), and (2) normalized cs followed a power law behavior not seen in absence of vascular outgrowths (ANOVA test, P < 0.0001). These results showed that vascular outgrowths acted as micro-obstacles altering the dispersion relationships of propagating shear waves and that MRE could provide valuable information about microvascular changes.

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization.

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305-11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications.

Computation of axonal elongation in head trauma finite element simulation.

In the case of head trauma, elongation of axons is thought to result in brain damage and to lead to Diffuse Axonal Injuries (DAI). Mechanical parameters have been previously proposed as DAI metric. Typically, brain injury parameters are expressed in terms of pressure, shearing stresses or invariants of the strain tensor. Addressing axonal deformation within the brain during head impact can improve our understanding of DAI mechanisms. A new technique based on directional measurements of water diffusion in soft tissue using Magnetic Resonance Imaging (MRI), called Diffusion Tensor Imaging (DTI), provides information on axonal orientation within the brain. The present study aims at coupling axonal orientation from a 12-patient-based DTI 3D picture, called "DTI atlas", with the Strasbourg University Finite Element Head Model (SUFEHM). This information is then integrated in head trauma simulation by computing axonal elongation for each finite element of the brain model in a post-processing of classical simulation results. Axonal elongation was selected as computation endpoint for its strong potential as a parameter for DAI prediction and location. After detailing the coupling technique between DTI atlas and the head FE model, two head trauma cases presenting different DAI injury levels are reconstructed and analyzed with the developed methodology as an illustration of axonal elongation computation. Results show that anisotropic brain structures can be realistically implemented into an existing finite element model of the brain. The feasibility of integrating axon fiber direction information within a dedicated post-processor is also established in the context of the computation of axonal elongation. The accuracy obtained when estimating level and location of the computed axonal elongation indicates that coupling classical isotropic finite element simulation with axonal structural anisotropy is an efficient strategy. Using this method, tensile elongation of the axons can be directly invoked as a mechanism for Diffuse Axonal Injury.

In vivo liver tissue mechanical properties by Transient Elastography: comparison with Dynamic Mechanical Analysis.

Understanding the mechanical properties of human liver is one of the most critical aspects of its numerical modeling for medical applications or impact biomechanics. Generally, model constitutive laws come from in vitro data. However, the elastic properties of liver may change significantly after death and with time. Furthermore, in vitro liver elastic properties reported in the literature have often not been compared quantitatively with in vivo liver mechanical properties on the same organ. In this study, both steps are investigated on porcine liver. The elastic property of the porcine liver, given by the shear modulus G, was measured by both Transient Elastography (TE) and Dynamic Mechanical Analysis (DMA). Shear modulus measurements were realized on in vivo and in vitro liver to compare the TE and DMA methods and to study the influence of testing conditions on the liver viscoelastic properties. In vitro results show that elastic properties obtained by TE and DMA are in agreement. Liver tissue in the frequency range from 0.1 to 4 Hz can be modeled by a two-mode relaxation model. Furthermore, results show that the liver is homogeneous, isotropic and more elastic than viscous. Finally, it is shown in this study that viscoelastic properties obtained by TE and DMA change significantly with post mortem time and with the boundary conditions.

Experimental in vitro mechanical characterization of porcine Glisson's capsule and hepatic veins.

Understanding the mechanical properties of human liver is the most critical aspect of numerical modeling for medical applications and impact biomechanics. Many researchers work on identifying mechanical properties of the liver both in vivo and in vitro considering the high liver injury percentage in abdominal trauma and for easy detection of fatal liver diseases such as viral hepatitis, cirrhosis, etc. This study is performed to characterize mechanical properties of individual parts of the liver, namely Glisson's capsule and hepatic veins, as these parts are rarely characterized separately. The long term objective of this study is to develop a realistic liver model by characterizing individual parts and later integrating them. In vitro uniaxial quasi-static tensile tests are done on fresh unfrozen porcine hepatic parts for large deformations at the rate of 0.1mm/s with a Bose Electroforce 3200 biomaterials test instrument. Results show that mean values of small strain and large strain elastic moduli are 8.22 ± 3.42 and 48.15 ± 4.5 MPa for Glisson's capsule (30 samples) and 0.62 ± 0.41 and 2.81 ± 2.23 MPa for veins (20 samples), respectively, and are found to be in good agreement with data in the literature. Finally, a non-linear hyper-elastic constitutive law is proposed for the two separate liver constituents under study.

Multiplicative Jacobian Energy Decomposition method for fast porous visco-hyperelastic soft tissue model.

Simulating soft tissues in real time is a significant challenge since a compromise between biomechanical accuracy and computational efficiency must be found. In this paper, we propose a new discretization method, the Multiplicative Jacobian Energy Decomposition (MJED) which is an alternative to the classical Galerkin FEM (Finite Element Method) formulation. This method for discretizing non-linear hyperelastic materials on linear tetrahedral meshes leads to faster stiffness matrix assembly for a large variety of isotropic and anisotropic materials. We show that our new approach, implemented within an implicit time integration scheme, can lead to fast and realistic liver deformations including hyperelasticity, porosity and viscosity.

Fast porous visco-hyperelastic soft tissue model for surgery simulation: application to liver surgery.

Understanding and modeling liver biomechanics represents a significant challenge due to its complex nature. In this paper, we tackle this issue in the context of real-time surgery simulation where a compromise between biomechanical accuracy and computational efficiency must be found. We describe a realistic liver model including hyperelasticity, porosity and viscosity that is implemented within an implicit time integration scheme. To optimize its computation, we introduce the Multiplicative Jacobian Energy Decomposition (MJED) method for discretizing hyperelastic materials on linear tetrahedral meshes which leads to faster matrix assembly than the standard Finite Element Method. Visco-hyperelasticity is modeled by Prony series while the mechanical effect of liver perfusion is represented with a linear Darcy law. Dynamic mechanical analysis has been performed on 60 porcine liver samples in order to identify some viscoelastic parameters. Finally, we show that liver deformation can be simulated in real-time on a coarse mesh and study the relative effects of the hyperelastic, viscous and porous components on the liver biomechanics.

Fifty years of brain tissue mechanical testing: from in vitro to in vivo investigations.

Beginning in the 1960s many studies have been performed to investigate the mechanical properties of brain. In this paper we point out the difficulties linked with in vitro experimental protocols as well as the advantages of using recently developed non-invasive in vivo techniques, such as magnetic resonance elastography. Results of in vitro and in vivo work are compared, emphasizing the specificities and disparities of the in vitro as well as the in vivo results. In particular, a detailed discussion of the results obtained from dynamic shear experiments and magnetic resonance elastography is given before arriving at a tentative conclusion on the state of knowledge of the mechanical properties of brain.