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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., (© 2024 Institute of Physics and Engineering in Medicine.)

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., Competing Interests: Funding Support and Author Disclosures This work was supported by the Research Foundation Flanders under grants 1211620N and 12B3124N to Dr Caenen and grant G092318N to Dr Bézy. Dr Voigt holds a personal research mandate of the Research Foundation Flanders (1832922N). Dr Nightingale has intellectual property related to radiation force-based imaging technologies that has been licensed to Siemens, Samsung, and MicroElastic Ultrasound Systems. Dr Pernot has intellectual property related to SWE that has been licensed to eMyoSound. Dr Vos has an ongoing research collaboration with Mindray Ultrasound. Drs Voigt and Jan D’hooge have an ongoing research collaboration with GE Vingmed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2023. Springer Nature Limited.)

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., (© 2022 Institute of Physics and Engineering in Medicine.)

Shear wave elastography (SWE) has the potential to determine cardiac tissue stiffness from non-invasive shear wave speed measurements, important, e.g., for predicting heart failure. Previous studies showed that waves traveling in the interventricular septum (IVS) may display Lamb-like dispersive behaviour, introducing a thickness-frequency dependency in the wave speed. However, the IVS tapers across its length, which complicates wave speed estimation by introducing an additional variable to account for. The goal of this work is to assess the impact of tapering thickness on SWE. The investigation is performed by combining in vitro experiments with acoustic radiation force (ARF) and 2D finite element simulations, to isolate the effect of the tapering curve on ARF-induced and natural waves in the heart. The experiments show a 11% deceleration during propagation from the thick to the thin end of an IVS-mimicking tapered phantom plate. The numerical analysis shows that neglecting the thickness variation in the wavenumber-frequency domain can introduce errors of more than 30% in the estimation of the shear modulus, and that the exact tapering curve, rather than the overall thickness reduction, determines the dispersive behaviour of the wave. These results suggest that septal geometry should be accounted for when deriving cardiac stiffness with SWE.

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.

Shear wave elastography (SWE) might allow non-invasive assessment of cardiac stiffness by relating shear wave propagation speed to material properties. However, after aortic valve closure, when natural shear waves occur in the septal wall, the stiffness of the muscle decreases significantly, and the effects of such temporal variation of medium properties on shear wave propagation have not been investigated yet. The goal of this work is to fundamentally investigate these effects. To this aim, qualitative results were first obtained experimentally using a mechanical setup, and were then combined with quantitative results from finite difference simulations. The results show that the amplitude and period of the waves increase during propagation, proportional to the relaxation of the medium, and that reflected waves can originate from the temporal stiffness variation. These general results, applied to literature data on cardiac stiffness throughout the heart cycle, predict as a major effect a period increase of 20% in waves propagating during a healthy diastolic phase, whereas only a 10% increase would result from the impaired relaxation of an infarcted heart. Therefore, cardiac relaxation can affect the propagation of waves used for SWE measurements and might even provide direct information on the correct relaxation of a heart.

For the quantification of myocardial function, myocardial stiffness can potentially be measured non-invasively using shear wave elastography. Clinical diagnosis requires high precision. In 10 healthy volunteers, we studied the reproducibility of the measurement of propagation speeds of shear waves induced by aortic and mitral valve closure (AVC, MVC). Inter-scan was slightly higher but in similar ranges as intra-scan variability (AVC: 0.67 m/s (interquartile range [IQR]: 0.40-0.86 m/s) versus 0.38 m/s (IQR: 0.26-0.68 m/s), MVC: 0.61 m/s (IQR: 0.26-0.94 m/s) versus 0.26 m/s (IQR: 0.15-0.46 m/s)). For AVC, the propagation speeds obtained on different day were not statistically different (p = 0.13). We observed different propagation speeds between 2 systems (AVC: 3.23-4.25 m/s [Zonare ZS3] versus 1.82-4.76 m/s [Philips iE33]), p = 0.04). No statistical difference was observed between observers (AVC: p = 0.35). Our results suggest that measurement inaccuracies dominate the variabilities measured among healthy volunteers. Therefore, measurement precision can be improved by averaging over multiple heartbeats., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision making, such that rt-PA is administered only to those individuals who would benefit from this treatment. Clot composition and structure affect the lytic efficacy of rt-PA and have an impact on elasticity. However, the relationship between clot elasticity and rt-PA lytic susceptibility has not been adequately investigated. The goal of this study was to quantify the relationship between clot elasticity and rt-PA susceptibility in vitro. Human and porcine highly retracted and mildly retracted clots were fabricated in glass pipettes. The rt-PA lytic susceptibility was evaluated in vitro using the percent clot mass loss. The Young's moduli of the clots were estimated using ultrasound-based single-track-location shear wave elasticity imaging. The percent mass loss in mildly retracted porcine and human clots (28.9 ± 6.1% and 45.2 ± 7.1%, respectively) was significantly higher (p < 0.05) than in highly retracted porcine and human clots (10.9 ± 2.1% and 25.5 ± 10.0%, respectively). Furthermore, the Young's moduli of highly retracted porcine and human clots (5.33 ± 0.92 and 3.21 ± 1.97 kPa, respectively) were significantly higher (p < 0.05) than those of mildly retracted porcine and human clots (2.66 ± 0.55 and 0.79 ± 0.21 kPa, respectively). The results revealed an inverse relationship between the percent clot mass loss and Young's modulus. These findings motivate continued investigation of ultrasound-based methods to assess clot stiffness in order to predict rt-PA thrombolytic efficacy., (Copyright © 2018 World Federation for Ultrasound in Medicine 8 Biology. Published by Elsevier Inc. All rights reserved.)

The propagation velocity of shear waves relates to tissue stiffness. We prove that a regular clinical cardiac ultrasound system can determine shear wave velocity with a conventional unmodified tissue Doppler imaging (TDI) application. The investigation was performed on five tissue phantoms with different stiffness using a research platform capable of inducing and tracking shear waves and a clinical cardiac system (Philips iE33, achieving frame rates of 400-700 Hz in TDI by tuning the normal system settings). We also tested the technique in vivo on a normal individual and on typical pathologies modifying the consistency of the left ventricular wall. The research platform scanner was used as reference. Shear wave velocities measured with TDI on the clinical cardiac system were very close to those measured by the research platform scanner. The mean difference between the clinical and research systems was 0.18 ± 0.22 m/s, and the limits of agreement, from -0.27 to +0.63 m/s. In vivo, the velocity of the wave induced by aortic valve closure in the interventricular septum increased in patients with expected increased wall stiffness., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Ultrasound contrast agent (UCA) imaging provides a cost-effective diagnostic tool to assess tissue perfusion and vascular pathologies. However, excessive transmission (TX) levels may negatively impact both uniform diffusion and survival rates of contrast agents, limiting their density and thus their echogenicity. Contrast detection methods with both high sensitivity and low-contrast destruction rate are thus essential to maintain diagnostic capabilities. Plane-wave TX with a high number of compounding angles has been suggested to produce good quality images at pressure levels that do not destroy UCA. In this paper, we performed a quantitative evaluation of detection efficacy of flowing UCA with either traditional focused scanning or ultrafast plane-wave imaging. Amplitude modulation (AM) at nondestructive pressure levels was implemented in the ULA-OP ultrasound research platform. The influence of the number of compounding angles, peak-negative pressure, and flow speed on the final image quality was investigated. Results show that the images obtained by compounding multiple angled plane waves offer a greater contrast (up to a 12-dB increase) with respect to focused AM. This increase is attributed mainly to noise reduction caused by the coherent summation in the compounding step. Additionally, we show that highly sensitive detection is already achieved with a limited compounding number ( ), thus suggesting the feasibility of continuous contrast monitoring at a high frame rate. This capability is essential to properly detect contrast agents flowing at high speed, as an excessive angle compounding is shown to be destructive for the contrast signal, as the UCA motion quickly causes loss of correlation between consecutive echoes.