Achieving environmental stability in an atomically thin quantum spin Hall insulator via graphene intercalation.

Atomic monolayers on semiconductor surfaces represent an emerging class of functional quantum materials in the two-dimensional limit - ranging from superconductors and Mott insulators to ferroelectrics and quantum spin Hall insulators. Indenene, a triangular monolayer of indium with a gap of ~ 120 meV is a quantum spin Hall insulator whose micron-scale epitaxial growth on SiC(0001) makes it technologically relevant. However, its suitability for room-temperature spintronics is challenged by the instability of its topological character in air. It is imperative to develop a strategy to protect the topological nature of indenene during ex situ processing and device fabrication. Here we show that intercalation of indenene into epitaxial graphene provides effective protection from the oxidising environment, while preserving an intact topological character. Our approach opens a rich realm of ex situ experimental opportunities, priming monolayer quantum spin Hall insulators for realistic device fabrication and access to topologically protected edge channels.

In Vitro Evaluation of Real-Time Viscoelastic and Coagulation Properties of Various Classes of Topical Hemostatic Agents Using a Novel Contactless Nondestructive Technology.

Hemorrhaging is the main cause of death among combat and civilian injuries and has significant clinical and economic consequences. Despite their vital roles in bleeding management, an optimal topical hemostatic agent (HA) has yet to be developed for a particular scenario. This is partly due to a lack of an overarching quantitative testing technology to characterize the various classes of HAs in vitro. Herein, the feasibility of a novel, contactless, and nondestructive technique to quantitatively measure the shear storage modulus (G') and clotting properties of whole blood in contact with different dosages of eight topical HAs, including particulates and gauze-like and sponge-like systems, was assessed. The real-time G'-time profiles of these blood/HA systems revealed their distinct biomechanical behavior to induce and impact coagulation. These were analyzed to characterize the clot initiation time, clotting rate, clotting time, and apparent stiffness of the formed clots (both immediately and temporally), which were correlated with their reported hemostatic mechanisms of action. Moreover, the HAs that worked independently from the natural blood clotting cascade were identified and quantified through this technology. In sum, this study indicated that the nondestructive nature of the technology may offer a promising tool for accurate, quantitative in vitro measurements of the clotting properties of various classes of HAs, which may be used to better predict their in vivo outcomes.

Validation and application of a nondestructive and contactless method for rheological evaluation of biomaterials.

Hydrogels are extensively used for tissue engineering, cell therapy or controlled release of bioactive factors. Nondestructive techniques that can follow their viscoelastic properties during polymerization, remodeling, and degradation are needed, since these properties are determinant for their in vivo efficiency. In this work, we proposed the viscoelastic testing of bilayered materials (VeTBiM) as a new method for nondestructive and contact-less mechanical characterization of soft materials. The VeTBiM method measures the dynamic displacement response of a material, to a low amplitude vibration in order to characterize its viscoelastic properties. We validated VeTBiM by comparing data obtained on various agar and chitosan hydrogels with data from rotational rheometry, and compression tests. We then investigated its potential to follow the mechanical properties of chitosan hydrogels during gelation and in the presence of papain and lysozyme that induce fast or slow enzymatic degradation. Due to this nondestructive and contactless approach, samples can be removed from the instrument and stored in different conditions between measurements. VeTBiM is well adapted to follow biomaterials alone or with cells, over long periods of time. This new method will help in the fine tuning of the mechanical properties of biomaterials used for cell therapy and tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2565-2573, 2017.

Rheological assessment of a polymeric spherical structure using a three-dimensional shear wave scattering model in dynamic spectroscopy elastography.

With the purpose of assessing localized rheological behavior of pathological tissues using ultrasound dynamic elastography, an analytical shear wave scattering model was used in an inverse problem framework. The proposed method was adopted to estimate the complex shear modulus of viscoelastic spheres from 200 to 450 Hz. The inverse problem was formulated and solved in the frequency domain, allowing assessment of the complex viscoelastic shear modulus at discrete frequencies. A representative rheological model of the spherical obstacle was determined by comparing storage and loss modulus behaviors with Kelvin-Voigt, Maxwell, Zener, and Jeffrey models. The proposed inversion method was validated by using an external vibrating source and acoustic radiation force. The estimation of viscoelastic properties of three-dimensional spheres made softer or harder than surrounding tissues did not require a priori rheological assumptions. The proposed method is intended to be applied in the context of breast cancer imaging.

Viscoelastic characterization of elliptical mechanical heterogeneities using a semi-analytical shear-wave scattering model for elastometry measures.

This paper presents a semi-analytical model of shear wave scattering by a viscoelastic elliptical structure embedded in a viscoelastic medium, and its application in the context of dynamic elastography imaging. The commonly used assumption of mechanical homogeneity in the inversion process is removed introducing a priori geometrical information to model physical interactions of plane shear waves with the confined mechanical heterogeneity. Theoretical results are first validated using the finite element method for various mechanical configurations and incidence angles. Secondly, an inverse problem is formulated to assess viscoelastic parameters of both the elliptic inclusion and its surrounding medium, and applied in vitro to characterize mechanical properties of agar-gelatin phantoms. The robustness of the proposed inversion method is then assessed under various noise conditions, biased geometrical parameters and compared to direct inversion, phase gradient and time-of-flight methods. The proposed elastometry method appears reliable in the context of estimating confined lesion viscoelastic parameters.

Shear wave induced resonance elastography of venous thrombi: a proof-of-concept.

Shear wave induced resonance elastography (SWIRE) is proposed for deep venous thrombosis (DVT) elasticity assessment. This new imaging technique takes advantage of properly polarized shear waves to induce resonance of a confined mechanical heterogeneity. Realistic phantoms (n = 9) of DVT total and partial clot occlusions with elasticities from 406 to 3561 Pa were built for in vitro experiments. An ex vivo study was also performed to evaluate the elasticity of two fresh porcine venous thrombi in a pig model. Transient shear waves at 45-205 Hz were generated by the vibration of a rigid plate (plane wavefront) or by a needle to simulate a radiation pressure on a line segment (cylindrical wavefront). Induced propagation of shear waves was imaged with an ultrafast ultrasound scanner and a finite element method was developed to simulate tested experimental conditions. An inverse problem was then formulated considering the first resonance frequency of the DVT inclusion. Elasticity agreements between SWIRE and a reference spectroscopy instrument (RheoSpectris) were found in vitro for total clots either in plane (r(2) = 0.989) or cylindrical (r(2) = 0.986) wavefront configurations. For total and partial clots, elasticity estimation errors were 9.0 ±4.6% and 9.3 ±11.3%, respectively. Ex vivo, the blood clot elasticity was 498 ±58 Pa within the inferior vena cava and 436 ±45 Pa in the right common iliac vein (p = 0.22). To conclude, the SWIRE technique seems feasible to quantitatively assess blood clot elasticity in the context of DVT ultrasound imaging.

Shear wave induced resonance elastography of spherical masses with polarized torsional waves.

Shear Wave Induced Resonance (SWIR) is a technique for dynamic ultrasound elastography of confined mechanical inclusions. It was developed for breast tumor imaging and tissue characterization. This method relies on the polarization of torsional shear waves modeled with the Helmholtz equation in spherical coordinates. To validate modeling, an in vitro set-up was used to measure and image the first three eigenfrequencies and eigenmodes of a soft sphere. A preliminary in vivo SWIR measurement on a breast fibroadenoma is also reported. Results revealed the potential of SWIR elastography to detect and mechanically characterize breast lesions for early cancer detection.

Hyper-frequency viscoelastic spectroscopy of biomaterials.

With the emergence of new biomaterials and elastography imaging techniques, there is a need for innovative instruments dedicated to viscoelasticity measurements. In this work, we introduce a novel hyper-frequency viscoelastic spectroscopy (HFVS) technique dedicated to characterize soft media subjected to mid-to-very-high frequency stress ranges (or, equivalently, to probe short-to-very-short relaxation times). HFVS, which has been implemented in an analytical instrument performing non-contact measurements in less than 1 s between 10 and 1000 Hz, is a suitable tool to study viscoelasticity for bio-applications. In this context, HFVS has been compared to classical oscillatory rheometry on several classes of soft materials currently encountered in tissue repair, bioengineering and elastography imaging on a frequency range between 10 and 100 Hz. After having demonstrated the good correspondence between HFVS and rheometry, this study has been completed by exploring the sensitivity of HFVS to physicochemically induced variations of viscoelasticity. HFVS opens promising perspectives in the challenging field of biomaterial science and for viscoelasticity-based quality control of materials.

Characterization of blood clot viscoelasticity by dynamic ultrasound elastography and modeling of the rheological behavior.

Dynamic elastography (DE) is a new tool to study mechanical behavior of soft tissues via their motion response to propagating shear waves. This technique characterized viscoelasticity of 9 porcine whole blood samples (3 animals) during coagulation for a shearing frequency of 70Hz, and after complete clot formation between 50 and 160Hz. Clot storage (G') and loss (G″) moduli were calculated from shear wave velocity and attenuation. Temporal evolutions of G' and G″ during coagulation were typified with 4 parameters: maximum change in elasticity (G' slope(max)), elasticity after 120min of coagulation (G'(max)), time occurrence of G″ maximum (t(e)) and G″ at the plateau (G″(plateau)). G' and G″ frequency dependence of completely formed blood clots was fitted with 5 standard rheological models: Maxwell, Kelvin-Voigt, Jeffrey, Zener and third-order generalized Maxwell. DE had sufficient sensitivity to follow the coagulation kinetics described by a progressive increase in G', while G″ transitory increased followed by a rapid stabilization. Inter- and intra-animal dispersions (InterAD and IntraAD) of G'(max) (InterAD=15.9%, IntraAD=9.1%) showed better reproducibility than G' slope(max) (InterAD=40.4%, IntraAD=21.9%), t(e) (InterAD=27.4%, IntraAD=18.7%) and G″(plateau) (InterAD=58.6%, IntraAD=40.2%). G' evolution within the considered range of frequency exhibited an increase, followed by stabilization to a plateau, whereas G″ presented little variations with convergence at a quasi-constant value at highest frequencies. Residues χ(⁎), describing the goodness of fit between models and experimental data, showed statistically (p<0.05) that the Kelvin-Voigt model was less in agreement with experimental data than other models. The Zener model is recommended to predict G' and G″ dispersion of coagulated blood over the explored frequency range.

Ultrasound dynamic micro-elastography applied to the viscoelastic characterization of soft tissues and arterial walls.

Quantitative noninvasive methods that provide in vivo assessment of mechanical characterization of living tissues, organs and artery walls are of interest because information on their viscoelastic properties in the presence of disease can affect diagnosis and treatment options. This article proposes the dynamic micro-elastography (DME) method to characterize viscoelasticity of small homogeneous soft tissues, as well as the adaptation of the method for vascular applications [vascular dynamic micro-elastography (VDME)]. The technique is based on the generation of relatively high-frequency (240-1100 Hz) monochromatic or transient plane shear waves within the medium and the tracking of these waves from radio-frequency (RF) echoes acquired at 25 MHz with an ultrasound biomicroscope (Vevo 770, Visualsonics). By employing a dedicated shear wave gated strategy during signal acquisition, postprocessed RF sequences could achieve a very high frame rate (16,000 images per s). The proposed technique successfully reconstructed shear wave displacement maps at very high axial (60 mum) and lateral (250 mum) spatial resolutions for motions as low as a few mum. An inverse problem formulated as a least-square minimization, involving analytical simulations (for homogenous and vascular geometries) and experimental measurements were performed to retrieve storage (G') and loss (G'') moduli as a function of the shearing frequency. Viscoelasticity measurements of agar-gelatin materials and of a small rat liver were proven feasible. Results on a very thin wall (3 mm thickness) mimicking artery enabled to validate the feasibility and the reliability of the vascular inverse problem formulation. Subsequently, the G' and G'' of a porcine aorta showed that both parameters are strongly dependent on frequency, suggesting that the vascular wall is mechanically governed by complex viscoelastic laws.

Shear wave induced resonance elastography of soft heterogeneous media.

In the context of ultrasound dynamic elastography imaging and characterization of venous thrombosis, we propose a method to induce mechanical resonance of confined soft heterogeneities embedded in homogenous media. Resonances are produced by the interaction of horizontally polarized shear (SH) waves with the mechanical heterogeneity. Due to such resonance phenomenon, which amplifies displacements up to 10 times compared to non-resonant condition, displacement images of the underlying structures are greatly contrasted allowing direct segmentation of the heterogeneity and a more precise measurement of displacements since the signal-to-noise ratio is enhanced. Coupled to an analytical model of wave scattering, the feasibility of shear wave induced resonance (SWIR) elastography to characterize the viscoelasticity of a mimicked venous thrombosis is demonstrated (with a maximum variability of 3% and 11% for elasticity and viscosity, respectively). More generally, the proposed method has the potential to characterize the viscoelastic properties of a variety of soft biological and industrial materials.

3D estimation of soft biological tissue deformation from radio-frequency ultrasound volume acquisitions.

The current research and development of 2D (matrix-shaped) transducer arrays to acquire 3D ultrasound data sets provides new insights into medical ultrasound applications and in particular into elastography. Until very recently, tissue strain estimation techniques commonly used in elastography were mainly 1D or 2D methods. In this paper, a 3D technique estimating biological soft tissue deformation under load from ultrasound radiofrequency volume acquisitions is introduced. This method locally computes axial strains, while considering lateral and elevational motions. Optimal deformation parameters are estimated as those maximizing a similarity criterion, defined as the normalized correlation coefficient, between an initial region and its deformed version, when the latter is compensated for according to these parameters. The performance of our algorithm was assessed with numerical data reproducing the configuration of breast cancer, as well as a physical phantom mimicking a pressure ulcer. Simulation results show that the estimated strain fields are very close to the theoretical values, perfectly discriminating between the harder lesion and the surrounding medium. Experimental strain images of the physical phantom demonstrated the different structures of the medium, even though they are not all detectable on the ultrasound scans. Finally, both simulated and experimental results demonstrate the ability of our algorithm to provide good-quality elastograms, even in the conditions of significant out-of-plane motion.

Three-dimensional transient and harmonic shear-wave scattering by a soft cylinder for dynamic vascular elastography.

With the objective of characterizing biological soft tissues with dynamic elastography, a three-dimensional (3D) analytical model is proposed to simulate the scattering of plane shear waves by a soft cylinder embedded in an infinite soft medium. The 3D problem of harmonic plane shear-wave scattering is first formulated and solved, and the monochromatic solution is employed to simulate transient wave scattering. Both harmonic and transient simulations are compared with experimental 3D acquisitions. The good agreements obtained between measured and calculated displacement fields allowed to conclude on the validity of the proposed 3D harmonic and transient models. The spatial distribution of displacements (diffraction lobes, displacement oscillations, wave diffraction angles, etc.) and their relative amplitudes in both inclusion and surrounding materials depended on the contrast between the viscoelastic properties of the different media. The possibility of solving an inverse problem to assess soft heterogeneous medium viscoelasticity is discussed and some future theoretical and experimental developments are proposed.

Performance evaluation of different implementations of the Lagrangian speckle model estimator for non-invasive vascular ultrasound elastography.

Non-invasive vascular ultrasound elastography (NIVE) was recently introduced to characterize mechanical properties of carotid arteries for stroke prevention. Using the Lagrangian speckle model estimator (LSME), the four components of the 2D deformation matrix (delta), which are the axial strain (delta(yy)) and shear (delta(yx)) and the lateral strain (delta(xx)) and shear (delta(xy)), can be computed. This paper overviews four different implementations of the LSME and addresses their reliability. These implementations include two unconstrained (L&M and L&M+) and one constrained (ITER(c)) iterative algorithms, and one optical flow-based (OF-based) algorithm. The theoretical frameworks were supported by biomechanical simulations of a pathology-free vessel wall and by one single layer vessel-mimicking phantom study. Regarding simulations, the four LSME implementations provided similar biases on axial motion parameters, except the L&M that outperformed other methods with a minimum strain bias of -3%. LSME axial motion estimates showed good consistence with theory, namely the OF-based algorithm that in a specific instance estimated delta(yy) with no relative error on the standard deviation. With regards to lateral motion parameters, ITER(c) exhibited a minimum strain bias of -8.5% when ultrasound beam and motion mostly run parallel, whereas L&M performs strain and shear estimates with less than 23% bias independently of orientations. The in vitro vessel phantom data showed LSME delta(yy) and delta(yx) maps that were qualitatively equivalent to theory, and noisy delta(xx) and delta(xy) elastograms. In summary, the authors propose to promote the OF-based LSME as an optimal choice for further applications of NIVE, because of its reliability to compute both axial strain and shear motion parameters and because it outperformed the other implementations by a factor of 30 or more in terms of processing time.

3D ultrasound elastography for early detection of lesions. evaluation on a pressure ulcer mimicking phantom.

A pressure ulcer is a damaged tissue area induced by an unrelieved pressure compressing the tissue during a prolonged period of immobility. The lack of information and studies on the development of this pathology makes its prevention difficult. However, it is both acknowledged that lesions initiate in the deep muscular tissues before they expand to the skin, and that lesions are harder than healthy tissues. Elastography is therefore an interesting tool for an early detection of the pathology. A 3D strain estimation algorithm is presented and evaluated on a PVA-cryogel phantom, mimicking a pressure ulcer at an early stage.

Noninvasive vascular elastography: toward a complementary characterization tool of atherosclerosis in carotid arteries.

Only a minority of patients with carotid arterial disease have warning symptoms, because the majority of strokes are caused by previously asymptomatic lesions. Because morbidity and mortality after acute stroke are high, patients should be diagnosed and treated before symptoms develop. The hypothesis of this study is that vascular elasticity maps (or elastograms) of carotids are of predictive value for plaque characterization. The strain tensor from either cross-sectional or longitudinal ultrasound radiofrequency data were assessed by a new implementation of the Lagrangian speckle model estimator (LSME), which considers local echogenicity variations. A 26-year-old healthy male (HS1), a 40-year-old (HS2) normal female subject and two 75-year-old asymptomatic patients with severe carotid stenoses were scanned. Reproducible elastograms were obtained as a function of time over five to seven cardiac cycles. Stress-strain modulus elastograms were computed for normal subjects. Stiffening of healthy carotid walls was estimated to be 148 +/- 7 kPa and 163 +/- 30 kPa at peak-systole for HS1 and HS2, respectively. For patients with heterogeneous plaques, strain and shear elastograms revealed interesting information about plaque size, tissue composition and mechanical interaction between structures. In conclusion, the LSME provides a promising approach for strain and shear estimates to characterize vulnerable plaque.

Estimation of polyvinyl alcohol cryogel mechanical properties with four ultrasound elastography methods and comparison with gold standard testings.

Tissue-mimicking phantoms are very useful in the field of tissue characterization and essential in elastography for the purpose of validating motion estimators. This study is dedicated to the characterization of polyvinyl alcohol cryogel (PVA-C) for these types of applications. A strict fabrication procedure was defined to optimize the reproducibility of phantoms having a similar elasticity. Following mechanical stretching tests, the phantoms were used to compare the accuracy of four different elastography methods. The four methods were based on a one-dimensional (1-D) scaling factor estimation, on two different implementations of a 2-D Lagrangian speckle model estimator (quasistatic elastography methods), and on a 1-D shear wave transient elastography technique (dynamic method). Young's modulus was investigated as a function of the number of freeze-thaw cycles of PVA-C, and of the concentration of acoustic scatterers. Other mechanical and acoustic parameters-such as the speed of sound, shear wave velocity, mass density, and Poisson's ratio-also were assessed. The Poisson's ratio was estimated with good precision at 0.499 for all samples, and the Young's moduli varied in a range of 20 kPa for one freeze-thaw cycle to 600 kPa for 10 cycles. Nevertheless, above six freeze-thaw cycles, the results were less reliable because of sample geometry artifacts. However, for the samples that underwent less than seven freeze-thaw cycles, the Young's moduli estimated with the four elastography methods showed good matching with the mechanical tensile tests with a regression coefficient varying from 0.97 to 1.07, and correlations R2 varying from 0.93 to 0.99, depending on the method.