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VisR ultrasound characterizes the viscoelastic properties of tissue by fitting acoustic radiation force (ARF)-induced displacements in the region of ARF excitation to a 1D mass-spring-damper (MSD) model. Viscosity and elasticity are found separately from each other but relative to the applied ARF amplitude. We refer to these parameters as ‘relative elasticity (RE)’ and ‘relative viscosity (RV)’. We hypothesize that RE and RV linearly correlate to true elasticity and viscosity in tissue.

In transversely isotropic (TI) materials, mechanical properties differ along versus across the axis of symmetry (AoS). The degree of these directional differences has been interrogated by ultrasound-based measures of shear wave velocity (SWV) and ARFI peak displacements (PD) acquired along versus across the AoS. When performed using a conventional linear array transducer, such measurements require a 90o transducer rotation, which can be cumbersome and prone to misalignment errors. Rather than 90o, we hypothesize that smaller rotation angles can be used to assess mechanical anisotropy. This hypothesis was tested in silico using finite-element method (FEM) models and Field II. ARFI and Shear Wave Elasticity Imaging (SWEI) were simulated in five TI elastic materials with longitudinal versus transverse shear elastic modulus ratios (SRs) of 1.22 to 5.44. The simulated rotation angles were 15o, 30o, and 90o. The ratio of PD was measured with the long-axis of the ARF PSF aligned along the AoS versus long-axis rotated by 90o, 30o, or 15o from the AoS. The ratio of SWV was measured along the AoS versus 90o, 30o, or 15o rotation from the AoS. For a 90o rotation angle, both SWV and PD ratios were statistically different (2-sample t-test, p

Previous work has shown that the degree of anisotropy in tissue can be assessed using Acoustic Radiation Force Impulse (ARFI) imaging performed with a geometrically asymmetric excitation. In this work, we investigate the clinical relevance of mechanical anisotropy in Duchenne muscular dystrophy (DMD). Anisotropy assessment was performed using relative elasticity (RE) and relative viscosity (RV) parameters measured by Viscoelastic Response (VisR) ultrasound. These parameters were evaluated as the ratio of their respective values obtained with two orthogonal transducer orientations, i.e. parallel and perpendicular to the muscle fiber direction, to represent the transverse over the longitudinal RE or RV. In a pilot clinical feasibility study performed in six, 7.9–10.4 year-old boys with (DMD) and five age-matched boys with no known neuromuscular disorders, VisR anisotropy imaging was performed in vivo in the rectus femoris (RF) serially for a total of 22 time points in DMD and 12 time points in control boys. Both the RE and RV anisotropy ratios in the RF muscles of boys with DMD were significantly higher (Wilcoxon, p

While skeletal muscle is often assumed to be structurally transversely isotropic (TI), its mechanical anisotropy is not well characterized in vivo. VisR ultrasound, a technique that provides information about the viscoelastic mechanical response of tissue, can be used for such in vivo characterization. Specifically, VisR-derived Relative Elasticity (RE) provides directionally dependent information about the shear modulus of materials. We hypothesize that VisR RE can be used in healthy older adults and in stroke patients to 1) assess the degree of anisotropy (DoA) of the biceps brachii (BB) and 2) characterize the effect of passive loading on the BB. VisR imaging was performed in the BB long head of 2 healthy controls and 1 stroke patient. The subjects' arms were imaged in full extension and approximately 90° flexion at rest. Data were acquired in the transverse and longitudinal imaging planes at the medial location of the BB. The ratio of RE obtained in the transverse to the longitudinal muscle views was found to reflect the DoA in shear modulus, where DoA = 1 indicates perfect isotropy. In control subjects, RE values for flexion and extension in the transverse imaging plane (previously shown to reflect the longitudinal shear modulus, μL) were higher than the RE values in the longitudinal imaging plane (which, primarily reflects the transverse shear modulus, μT). Additionally, both the longitudinal and transverse shear moduli increased in extension vs. flexion. Both the magnitude and direction of anisotropy appeared to change in the stroke patient compared to the healthy controls. This work indicates VisR can be used to assess DoA in skeletal muscle of older adults and examine effects of passive loading on mechanical properties, in vivo, which may be clinically relevant to studying impairment post stroke.

In Duchenne muscular dystrophy (DMD), muscle fiber necrosis and subsequent progressive replacement of muscle by fibrous tissue and fat impacts the degree of anisotropy (DoA) in mechanical properties. Mechanical DoA can be assessed in skeletal muscle using Viscoelastic Response (VisR) ultrasound. We hypothesize that in vivo VisR DoA measures in the rectus femoris (RF) muscles of boys with DMD statistically differ from those in control boys. Further, we hypothesize that VisR DoA is correlated to RF functional output.

Tissue mechanical anisotropy has been shown to be diagnostically relevant in numerous clinical applications. Anisotropy can be assessed using acoustic radiation force-based techniques, including Acoustic Radiation Force Impulse (ARFI) and Viscoelastic Response (VisR) ultrasound. In this work, ARFI peak displacement (PD), as well as VisR relative elasticity (RE) and relative viscosity (RV), were implemented to image mechanical anisotropy in ex vivo porcine posas major muscle. Two psoas major samples were imaged in this work. The first sample was imaged whole. The second sample was sectioned into a 1 cm-diameter cylinder (with cylinder height oriented along the muscle fibers) and embedded into an isotropic gelatin phantom for imaging. ARFI and VisR were performed on both muscle samples using a linear array transducer mounted to a translation and rotation stage. By rotating the transducer 90o as it stepped across a 2D imaging field of view, PD, RE, and RV were measured along and across muscle fibers. Then, the ratios of PD, RE, and RV measurements made along versus across the muscle fibers were calculated, and these ratios were parametrically rendered in to 2D images representing degree of anisotropy. In the whole psoas major, PD anisotropy ratio was 1.08 +− 0.11, the RE anisotropy ratio was 0.94 +− 0.09 and the RV ratio was 0.94 +− 0.08. These PD and RE anisotropy ratios suggest that the longitudinal shear elastic modulus was greater than the transverse shear elastic modulus, which agrees with previous studies on muscle anisotropy. The RV results suggest that the longitudinal viscous modulus was greater than the transverse viscous modulus. Similar PD, RE, and RV anisotropy ratios were measured in the embedded psoas major section, and contrast ratios were 0.21, 0.14, and 0.30 for PD, RE and RV 2D anisotropy images, respectively. CNR for PD, RE, and RV anisotropy images were 3.26, 2.09 and 2.41, respectively. These results demonstrate that ARFI and VisR anisotropy imaging are relevant for delineating the spatial distribution of anisotropic features in tissue.

Degree of anisotropy (DoA) has been evaluated for clinical significance in several organs. In skeletal muscle, mechanical DoA has been shown to increase with passive extension, i.e. the shear modulus parallel to muscle fibers (μ l ) increases relative to that perpendicular (μ t ). Imaging such variations in DoA could facilitate diagnosing and monitoring muscle pathologies. We have previously demonstrated the feasibility of imaging DoA with VisR ultrasound, in silico. The purpose of this work is to experimentally demonstrate VisR DoA imaging ex vivo in pig and in vivo in human muscles. We hypothesize that 2D VisR anisotropy images represent mechanical anisotropy in muscle.

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of elastic anisotropy in kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate a novel method for selectively exploiting or obviating elastic anisotropy in kidney using Acoustic Radiation Force Impulse (ARFI)-induced peak displacement (PD). The kidneys of three pigs were imaged in vivo at baseline, with venous ligation, and with arterial ligation, and then kidneys were extracted and imaged ex vivo. Imaging was performed with ARF excitation impulses having F/1.5 or F/5.0 focal configurations, and data were acquired with the transducer oriented along and across nephrons alignment in the renal cortex. In addition to ARFI PD, shear wave velocity was measured along and across nephrons to estimate longitudinal and transverse shear elastic moduli. Elastic anisotropy was then assessed as the ratio of PD across versus along nephrons, and as the ratio of shear moduli along versus across nephrons. PD ratio using the F/1.5 ARF linearly correlated with shear moduli ratio (R2 = 0.95). However, PD ratio using the F/5.0 ARF was approximately 1.0 and had weak correlation to shear moduli ratio (R2= 0.56). Further, the average difference in PD measured along versus across nephrons was 2.91 μm for the F/1.5 ARF but was 0.2 μm for the F/5.0 ARF. These results suggest that the F/1.5 ARF excitation exploited elastic anisotropy in the renal cortex, while the F/5.0 ARF excitation obviated it.

Point shear wave elastography (pSWE) provides noninvasive measures of mechanical stiffness of biological tissue. Over the past decade, research has demonstrated that pSWE is effective at diagnosing a multitude of pathologies such as liver fibrosis and cancer. Life science researchers stand to benefit tremendously from access to pSWE but a number of challenges have limited its use in small animals. First, high frequency pSWE imaging suffers from transducer heating challenges and bandwidth requirements. Second, pSWE measurements are highly susceptible to variations in the environment and operator (e.g. precompression of tissue, transducer placement, etc.) which bias measurements and introduce error. Therefore, the objective of this work is to develop a robotically controlled, non-contact pSWE system capable of measuring liver stiffness in rodents.

Stroke is commonly caused by thromboembolic events originating from ruptured carotid plaque, with rupture potential related to plaque composition. We have previously shown that soft (intraplaque hemorrhage/necrotic core) and stiff (collagen/calcium) plaque components are differentiated with high sensitivity and specificity by peak displacement (PD) in Acoustic Radiation Force Impulse (ARFI) imaging. However, PD showed low performance for distinguishing between soft and between stiff features. We hypothesize that soft and stiff feature delineation will be improved using a new ARFI outcome metric — the variance of acceleration (VoA). We test our hypothesis using histological validation.

VisR ultrasound characterizes the viscoelastic properties of tissue by fitting acoustic radiation force (ARF)-induced displacements in the region of ARF excitation to a 1D mass-spring-damper (MSD) model. By so doing, viscosity and elasticity are found separately from each other but relative to the applied ARF amplitude. We refer to these parameters as ‘relative elasticity (RE)’ and ‘relative viscosity (RV)’. We herein test the hypothesis that RE and RV linearly correlate to true elasticity and viscosity, in silico. VisR imaging was simulated in 144 homogeneous, isotropic, viscoelastic materials with varying elasticity and viscosity using finite element model (FEM) and Field II simulation. RE linearly correlated with shear elasticity of the modeled materials, with R2 = 1.0. For a given elasticity, RE values varied by 2.5% on average when the shear viscosity was changed from 0.1 to 1.3 Pa.s. Similarly, RV linearly correlated with shear viscosity (R2 ≥ 0.99); however, for a given viscosity, RV values varied by 112.7% on average when shear elasticity changed from 3.33 to 20 kPa. This high degree of variation in RV was due to complex 3D system inertia, with greater inertial effects in stiffer materials. This confounding impact of elasticity on RV was compensated by using the natural frequency parameter, ω. After so compensating, corrected RV varied by < 1.0% on average for a given viscosity when the shear elasticity changed from 3.3 to 20 kPa. These results suggest the potential of VisR ultrasound for independently evaluating elastic and viscous properties in tissue.

Stroke is commonly caused by thromboembolic events originating from a ruptured carotid plaque. Histological studies have shown that plaque rupture potential is related to plaque composition rather than degree of stenosis. The use of Acoustic Radiation Force Impulse (ARFI) ultrasound imaging has enabled assessment of carotid plaque composition and structure. In particular, a previous study has shown that ARFI-derived peak displacement (PD) can differentiate between soft (intraplaque hemorrhage/necrotic core) and stiff (collagen/calcium) plaque components with high sensitivity and specificity. However, PD showed low performance for distinguishing between soft and between stiff features. This study evaluates an alternative ARFI-derived parameter, variance of acceleration (VoA), for intraplaque feature delineation. This study analyzed 20 carotid plaques imaged in vivo in patients undergoing carotid endarterectomy (CEA). After imaging, CEA specimens were harvested for histological validation. VoA was statistically significantly different (Wilcoxon, p < 0.01) between all examined plaque features, including between intraplaque hemorrhage and necrotic core and between collagen and calcium. Results suggest that VoA analysis improves ARFI discrimination between soft and between stiff carotid plaque components that are related to vulnerability for rupture.