Ultrasound Shear Wave Elastography in Cardiology.

The advent of high-frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart's thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave.

Effect of interstitial fluid pressure on shear wave elastography: an experimental and computational study.

Objective. An elevated interstitial fluid pressure (IFP) can lead to strain-induced stiffening of poroelastic biological tissues. As shear wave elastography (SWE) measures functional tissue stiffness based on the propagation speed of acoustically induced shear waves, the shear wave velocity (SWV) can be used as an indirect measurement of the IFP. The underlying biomechanical principle for this stiffening behavior with pressurization is however not well understood, and we therefore studied how IFP affects SWV through SWE experiments and numerical modeling.Approach. For model set-up and verification, SWE experiments were performed while dynamically modulating IFP in a chicken breast. To identify the confounding factors of the SWV-IFP relationship, we manipulated the material model (linear poroelastic versus porohyperelastic), deformation assumptions (geometric linearity versus nonlinearity), and boundary conditions (constrained versus unconstrained) in a finite element model mimicking the SWE experiments.Main results. The experiments demonstrated a statistically significant positive correlation between the SWV and IFP. The model was able to reproduce a similar SWV-IFP relationship by considering an unconstrained porohyperelastic tissue. Material nonlinearity was identified as the primary factor contributing to this relationship, whereas geometric nonlinearity played a smaller role. The experiments also highlighted the importance of the dynamic nature of the pressurization procedure, as indicated by a different observed SWV-IFP for pressure buildup and relaxation, but its clinical relevance needs to be further investigated.Significance. The developed model provides an adaptable framework for SWE of poroelastic tissues and paves the way towards non-invasive measurements of IFP.

Uncertainty quantification of the wall thickness and stiffness in an idealized dissected aorta.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models. It is important to evaluate the impact of the corresponding uncertainty on the predicted wall deformations and stress, which are both key outcome indicators for treatment optimization. Therefore, a physiology-inspired finite element framework was proposed to model the wall deformation and stress of a type B aortic dissection at diastolic and systolic pressure. Based on this framework, 300 finite element analyses, sampled with a Latin hypercube, were performed to assess the global uncertainty, introduced by 4 uncertain wall thickness and stiffness input parameters, on 4 displacement and stress output parameters. The specific impact of each input parameter was estimated using Gaussian process regression, as surrogate model of the finite element framework, and a δ moment-independent analysis. The global uncertainty analysis indicated minor differences between the uncertainty at diastolic and systolic pressure. For all output parameters, the 4th quartile contained the major fraction of the uncertainty. The parameter-specific uncertainty analysis elucidated that the material stiffness and relative thickness of the dissected membrane were the respective main determinants of the wall deformation and stress. The uncertainty analysis provides insight into the effect of uncertain wall thickness and stiffness parameters on the predicted deformation and stress. Moreover, it emphasizes the need for probabilistic rather than deterministic predictions for clinical decision making in aortic dissections.

Continuous shear wave measurements for dynamic cardiac stiffness evaluation in pigs.

Ultrasound-based shear wave elastography is a promising technique to non-invasively assess the dynamic stiffness variations of the heart. The technique is based on tracking the propagation of acoustically induced shear waves in the myocardium of which the propagation speed is linked to tissue stiffness. This measurement is repeated multiple times across the cardiac cycle to assess the natural variations in wave propagation speed. The interpretation of these measurements remains however complex, as factors such as loading and contractility affect wave propagation. We therefore applied transthoracic shear wave elastography in 13 pigs to investigate the dependencies of wave speed on pressure-volume derived indices of loading, myocardial stiffness, and contractility, while altering loading and inducing myocardial ischemia/reperfusion injury. Our results show that diastolic wave speed correlates to a pressure-volume derived index of operational myocardial stiffness (R = 0.75, p < 0.001), suggesting that both loading and intrinsic properties can affect diastolic wave speed. Additionally, the wave speed ratio, i.e. the ratio of systolic and diastolic speed, correlates to a pressure-volume derived index of contractility, i.e. preload-recruitable stroke work (R = 0.67, p < 0.001). Measuring wave speed ratio might thus provide a non-invasive index of contractility during ischemia/reperfusion injury.

Transmural Wave Speed Gradient May Distinguish Intrinsic Myocardial Stiffening From Preload-Induced Changes in Operational Stiffness in Shear Wave Elastography.

BACKGROUND: Shear wave elastography (SWE) is a promising technique to non-invasively assess myocardial stiffness based on the propagation speed of mechanical waves. However, a high wave propagation speed can either be attributed to an elevated intrinsic myocardial stiffness or to a preload-induced increase in operational stiffness. OBJECTIVE: Our objective was to find a way to discriminate intrinsic myocardial stiffening from stiffening caused by an increased pressure in SWE. METHODS: We used the finite element method to study the shear wave propagation patterns when stiffness and/or pressure is elevated, compared to normal stiffness and pressure. Numerical findings were verified in a few human subjects. RESULTS: The transmural wave speed gradient was able to distinguish changes in intrinsic stiffness from those induced by differing hemodynamic load (a speed of ±3.2 m/s in parasternal short-axis (PSAX) view was associated with a wave speed gradient of -0.17 ± 0.15 m/s/mm when pressure was elevated compared to 0.04 ± 0.05 m/s/mm when stiffness was elevated). The gradient however decreased when stiffness increased (decrease with a factor 3 in PSAX when stiffness doubled at 20 mmHg). The human data analysis confirmed the presence of a wave speed gradient in a patient with elevated ventricular pressure. CONCLUSION: Cardiac SWE modeling is a useful tool to gain additional insights into the complex wave physics and to guide post-processing. The transmural differences in wave speed may help to distinguish loading-induced stiffening from intrinsic stiffness changes. SIGNIFICANCE: The transmural wave speed gradient has potential as a new diagnostic parameter for future clinical studies.

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops.

BACKGROUND: Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties. OBJECTIVES: This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method. METHODS: In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury. RESULTS: Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant ß (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001). CONCLUSIONS: Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

Comparing Myocardial Shear Wave Propagation Velocity Estimation Methods Based on Tissue Displacement, Velocity and Acceleration Data.

Shear wave elastography (SWE) is a promising technique used to assess cardiac function through the evaluation of cardiac stiffness non-invasively. However, in the literature, SWE varies in terms of tissue motion data (displacement, velocity or acceleration); method used to characterize mechanical wave propagation (time domain [TD] vs. frequency domain [FD]); and the metric reported (wave speed [WS], shear or Young's modulus). This variety of reported methodologies complicates comparison of reported findings and sheds doubt on which methodology better approximates the true myocardial properties. We therefore conducted a simulation study to investigate the accuracy of various SWE data analysis approaches while varying cardiac geometry and stiffness. Lower WS values were obtained by the TD method compared with the FD method. Acceleration-based WS estimates in the TD were systematically larger than those based on velocity (∼10% difference). These observations were confirmed by TD analysis of 32 in vivo SWE mechanical wave measurements. In vivo data quality is typically too low for accurate FD analysis. Therefore, our study suggests using acceleration-based TD analysis for in vivo SWE to minimize underestimation of the true WS and, thus, to maximize the sensitivity of SWE to detect stiffness changes resulting from pathology.

Phase and group velocities for shear wave propagation in an incompressible, hyperelastic material with uniaxial stretch.

Objective.Determining elastic properties of materials from observations of shear wave propagation is difficult in anisotropic materials because of the complex relations among the propagation direction, shear wave polarizations, and material symmetries. In this study, we derive expressions for the phase velocities of the SH and SV propagation modes as a function of propagation direction in an incompressible, hyperelastic material with uniaxial stretch.Approach.Wave motion is included in the material model by adding incremental, small amplitude motion to the initial, finite deformation. Equations of motion for the SH and SV propagation modes are constructed using the Cauchy stress tensor derived from the strain energy function of the material. Group velocities for the SH and SV propagation modes are derived from the angle-dependent phase velocities.Main results.Sample results are presented for the Arruda-Boyce, Mooney-Rivlin, and Isihara material models using model parameters previously determined in a phantom.Significance.Results for the Mooney-Rivlin and Isihara models demonstrate shear splitting in which the SH and SV propagation modes have unequal group velocities for propagation across the material symmetry axis. In addition, for sufficiently large stretch, the Arruda-Boyce and Isihara material models show cusp structures with triple-valued group velocities for the SV mode at angles of roughly 15° to the material symmetry axis.

Full Characterization of in vivo Muscle as an Elastic, Incompressible, Transversely Isotropic Material Using Ultrasonic Rotational 3D Shear Wave Elasticity Imaging.

Using a 3D rotational shear wave elasticity imaging (SWEI) setup, 3D shear wave data were acquired in the vastus lateralis of a healthy volunteer. The innate tilt between the transducer face and the muscle fibers results in the excitation of multiple shear wave modes, allowing for more complete characterization of muscle as an elastic, incompressible, transversely isotropic (ITI) material. The ability to measure both the shear vertical (SV) and shear horizontal (SH) wave speed allows for measurement of three independent parameters needed for full ITI material characterization: the longitudinal shear modulus µL , the transverse shear modulus µT , and the tensile anisotropy χE . Herein we develop and validate methodology to estimate these parameters and measure them in vivo, with µL = 5.77±1.00 kPa, µT = 1.93±0.41 kPa (giving shear anisotropy χµ = 2.11±0.92 ), and χE = 4.67±1.40 in a relaxed vastus lateralis muscle. We also demonstrate that 3D SWEI can be used to more accurately characterize muscle mechanical properties as compared to 2D SWEI.

Assessing cardiac stiffness using ultrasound shear wave elastography.

Shear wave elastography offers a new dimension to echocardiography: it measures myocardial stiffness. Therefore, it could provide additional insights into the pathophysiology of cardiac diseases affecting myocardial stiffness and potentially improve diagnosis or guide patient treatment. The technique detects fast mechanical waves on the heart wall with high frame rate echography, and converts their propagation speed into a stiffness value. A proper interpretation of shear wave data is required as the shear wave interacts with the intrinsic, yet dynamically changing geometrical and material characteristics of the heart under pressure. This dramatically alters the wave physics of the propagating wave, demanding adapted processing methods compared to other shear wave elastography applications as breast tumor and liver stiffness staging. Furthermore, several advanced analysis methods have been proposed to extract supplementary material features such as viscosity and anisotropy, potentially offering additional diagnostic value. This review explains the general mechanical concepts underlying cardiac shear wave elastography and provides an overview of the preclinical and clinical studies within the field. We also identify the mechanical and technical challenges ahead to make shear wave elastography a valuable tool for clinical practice.

A direct comparison of natural and acoustic-radiation-force-induced cardiac mechanical waves.

Natural and active shear wave elastography (SWE) are potential ultrasound-based techniques to non-invasively assess myocardial stiffness, which could improve current diagnosis of heart failure. This study aims to bridge the knowledge gap between both techniques and discuss their respective impacts on cardiac stiffness evaluation. We recorded the mechanical waves occurring after aortic and mitral valve closure (AVC, MVC) and those induced by acoustic radiation force throughout the cardiac cycle in four pigs after sternotomy. Natural SWE showed a higher feasibility than active SWE, which is an advantage for clinical application. Median propagation speeds of 2.5-4.0 m/s and 1.6-4.0 m/s were obtained after AVC and MVC, whereas ARF-based median speeds of 0.9-1.2 m/s and 2.1-3.8 m/s were reported for diastole and systole, respectively. The different wave characteristics in both methods, such as the frequency content, complicate the direct comparison of waves. Nevertheless, a good match was found in propagation speeds between natural and active SWE at the moment of valve closure, and the natural waves showed higher propagation speeds than in diastole. Furthermore, the results demonstrated that the natural waves occur in between diastole and systole identified with active SWE, and thus represent a myocardial stiffness in between relaxation and contraction.

Analysis of multiple shear wave modes in a nonlinear soft solid: Experiments and finite element simulations with a tilted acoustic radiation force.

Tissue nonlinearity is conventionally measured in shear wave elastography by studying the change in wave speed caused by the tissue deformation, generally known as the acoustoelastic effect. However, these measurements have mainly focused on the excitation and detection of one specific shear mode, while it is theoretically known that the analysis of multiple wave modes offers more information about tissue material properties that can potentially be used to refine disease diagnosis. This work demonstrated proof of concept using experiments and finite element simulations in a uniaxially stretched phantom by tilting the acoustic radiation force excitation axis with respect to the material's symmetry axis. Using this unique set-up, we were able to visualize two propagating shear wave modes across the stretch direction for stretches larger than 140%. Complementary simulations were performed using material parameters determined from mechanical testing, which enabled us to convert the observed shear wave behavior into a correct representative constitutive law for the phantom material, i.e. the Isihara model. This demonstrates the potential of measuring shear wave propagation in combination with shear wave modeling in complex materials as a non-invasive alternative for mechanical testing.

Parasternal Versus Apical View in Cardiac Natural Mechanical Wave Speed Measurements.

Shear wave speed measurements can potentially be used to noninvasively measure myocardial stiffness to assess the myocardial function. Several studies showed the feasibility of tracking natural mechanical waves induced by aortic valve closure in the interventricular septum, but different echocardiographic views have been used. This article systematically studied the wave propagation speeds measured in a parasternal long-axis and in an apical four-chamber view in ten healthy volunteers. The apical and parasternal views are predominantly sensitive to longitudinal or transversal tissue motion, respectively, and could, therefore, theoretically measure the speed of different wave modes. We found higher propagation speeds in apical than in the parasternal view (median of 5.1 m/s versus 3.8 m/s, , n = 9 ). The results in the different views were not correlated ( r = 0.26 , p = 0.49 ) and an unexpectedly large variability among healthy volunteers was found in apical view compared with the parasternal view (3.5-8.7 versus 3.2-4.3 m/s, respectively). Complementary finite element simulations of Lamb waves in an elastic plate showed that different propagation speeds can be measured for different particle motion components when different wave modes are induced simultaneously. The in vivo results cannot be fully explained with the theory of Lamb wave modes. Nonetheless, the results suggest that the parasternal long-axis view is a more suitable candidate for clinical diagnosis due to the lower variability in wave speeds.

An in silico framework to analyze the anisotropic shear wave mechanics in cardiac shear wave elastography.

Shear wave elastography (SWE) is a potential tool to non-invasively assess cardiac muscle stiffness. This study focused on the effect of the orthotropic material properties and mechanical loading on the performance of cardiac SWE, as it is known that these factors contribute to complex 3D anisotropic shear wave propagation. To investigate the specific impact of these complexities, we constructed a finite element model with an orthotropic material law subjected to different uniaxial stretches to simulate SWE in the stressed cardiac wall. Group and phase speed were analyzed in function of tissue thickness and virtual probe rotation angle. Tissue stretching increased the group and phase speed of the simulated shear wave, especially in the direction of the muscle fiber. As the model provided access to the true fiber orientation and material properties, we assessed the accuracy of two fiber orientation extraction methods based on SWE. We found a higher accuracy (but lower robustness) when extracting fiber orientations based on the location of maximal shear wave speed instead of the angle of the major axis of the ellipsoidal group speed surface. Both methods had a comparable performance for the center region of the cardiac wall, and performed less well towards the edges. Lastly, we also assessed the (theoretical) impact of pathology on shear wave physics and characterization in the model. It was found that SWE was able to detect changes in fiber orientation and material characteristics, potentially associated with cardiac pathologies such as myocardial fibrosis. Furthermore, the model showed clearly altered shear wave patterns for the fibrotic myocardium compared to the healthy myocardium, which forms an initial but promising outcome of this modeling study.

Investigating Shear Wave Physics in a Generic Pediatric Left Ventricular Model via In Vitro Experiments and Finite Element Simulations.

Shear wave elastography (SWE) is a potentially valuable tool to noninvasively assess ventricular function in children with cardiac disorders, which could help in the early detection of abnormalities in muscle characteristics. Initial experiments demonstrated the potential of this technique in measuring ventricular stiffness; however, its performance remains to be validated as complicated shear wave (SW) propagation characteristics are expected to arise due to the complex non-homogenous structure of the myocardium. In this work, we investigated the (i) accuracy of different shear modulus estimation techniques (time-of-flight (TOF) method and phase velocity analysis) across myocardial thickness and (ii) effect of the ventricular geometry, surroundings, acoustic loading, and material viscoelasticity on SW physics. A generic pediatric (10-15-year old) left ventricular model was studied numerically and experimentally. For the SWE experiments, a polyvinylalcohol replicate of the cardiac geometry was fabricated and SW acquisitions were performed on different ventricular areas using varying probe orientations. Additionally, the phantom's stiffness was obtained via mechanical tests. The results of the SWE experiments revealed the following trends for stiffness estimation across the phantom's thickness: a slight stiffness overestimation for phase speed analysis and a clear stiffness underestimation for the TOF method for all acquisitions. The computational model provided valuable 3-D insights in the physical factors influencing SW patterns, especially the surroundings (water), interface force, and viscoelasticity. In conclusion, this paper presents a validation study of two commonly used shear modulus estimators for different ventricular locations and the essential role of SW modeling in understanding SW physics in the pediatric myocardium.

A versatile and experimentally validated finite element model to assess the accuracy of shear wave elastography in a bounded viscoelastic medium.

The feasibility of shear wave elastography (SWE) in arteries for cardiovascular risk assessment remains to be investigated as the artery's thin wall and intricate material properties induce complex shear wave (SW) propagation phenomena. To better understand the SW physics in bounded media, we proposed an in vitro validated finite element model capable of simulating SW propagation, with full flexibility at the level of the tissue's geometry, material properties, and acoustic radiation force. This computer model was presented in a relatively basic set-up, a homogeneous slab of gelatin-agar material (4.35 mm thick), allowing validation of the numerical settings according to actual SWE measurements. The resulting tissue velocity waveforms and SW propagation speed matched well with the measurement: 4.46 m/s (simulation) versus 4.63 ± 0.07 m/s (experiment). Further, we identified the impact of geometrical and material parameters on the SW propagation characteristics. As expected, phantom thickness was a determining factor of dispersion. Adding viscoelasticity to the model augmented the estimated wave speed to 4.58 m/s, an even better match with the experimental determined value. This study demonstrated that finite element modeling can be a powerful tool to gain insight into SWE mechanics and will in future work be advanced to more clinically relevant settings.