This work demonstrates how tuning of processing parameters can minimize differences in shear wave speeds between ultrasound systems, transducers, and shear wave modes. Shear speeds were measured in the livers of 38 healthy volunteers and in 4 elasticity phantoms. Phantom and clinical data for each transducer and acquisition format were reprocessed offline using different permutations of five processing parameters. Prior to parameter optimization, statistically significant differences were seen between measurements acquired with a Siemens ACUSON S2000 and those acquired with the Siemens ACUSON Sequoia. Optimization of processing parameters was shown to be successful in eliminating significant differences between clinical systems, as well as differences between transducers and shear wave modes on the ACUSON Sequoia.

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics.

In Golden Retriever Muscular Dystrophy (GRMD) dogs, a relevant animal model of human Duchenne muscular dystrophy (DMD), skeletal muscles progressively inflame, necrose, and undergo fibrous and fatty deposition. These degenerative changes alter the composition and structure of muscle, which affects the degree of directional variation, or anisotropy, in tissue mechanical properties. Further, such degenerative changes alter the spatial distribution of mechanical property across muscles. In this work we investigate the relevance of mechanical anisotropy and texture, estimated using Viscoelastic Response (VisR) ultrasound, to tracking progressive dystrophic muscle degeneration in GRMD dogs, in vivo. In a year-long study of 20 dogs, degree of shear elastic anisotropy (DoA), was significantly higher in the GRMD semitendinosus (ST) muscle compared to control ST (GRMD: 1.23 +- 0.25, Control 1.13 +- 0.27, p<0.05, Wilcoxon). Also, VisR-derived textural entropy and heterogeneity indices were significantly different at 6, 9, and 12 months of age in the rectus femoris (RF) muscle, and at 12 months of age in the vastus lateralis (VL) muscle, of GRMD versus control. These results suggest that VisR-derived anisotropy estimates and texture features may be clinically relevant biomarkers for longitudinally tracking dystrophic muscle degeneration, in vivo.

Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscle degeneration involving necrosis and inflammation, with subsequent replacement of muscle fibers by fibrosis and fatty tissue. These compositional changes underlie mechanical property alterations in affected muscles, which may be assessed using Viscoelastic Response (VisR) ultrasound. We hypothesize that VisR will delineate differences in the viscoelastic properties of lower limb skeletal muscles in boys with versus without DMD. VisR imaging was performed in the vastus intermedius (VI), rectus femoris (RF), sartorius (SM) and gastrocnemius (GM) muscles of seven boys (4 DMD, 3 control) aged 7.9 - 10.4 years. Parametric images of relative elasticity (RE) and relative viscosity (RV) were rendered. From the parametric images, percent muscle area with relatively high RE or RV value was calculated and compared (Wilcoxon rank-sum) between DMD and control on a per-muscle basis. In the VI, RF and SM, percent muscle with relatively high RV was larger (VI: 17.7% v. 13.1% RF: 98.9% v. 93.7%, SM: 43.2% v. 40.6% p <; 0.05) in DMD than control muscles. In the VI, percent muscle with relatively high RE was larger (32.8% v. 29.5%, p <; 0.05) in DMD muscles. No significant differences were observed in the GM between DMD and control. VisR results were consistent with temporally-matched functional testing using a hand-held dynamometer, which showed 40.5% to 70.0% lower force output in DMD RF, VL and SM - and only 21.8% lower force output in DMD GM - relative to the corresponding control muscles. These results suggest that VisR imaging is relevant to delineating viscoelastic property alterations that are associated with dystrophic muscle degeneration in boys with DMD, in vivo.

Viscoelastic response (VisR) ultrasound is an acoustic radiation force (ARF)-based imaging method that fits induced displacements to a one-dimensional (1-D) mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic moduli, τ, in viscoelastic materials. Error in VisR τ estimation arises from inertia and acoustic displacement underestimation. These error sources are herein evaluated using finite-element method (FEM) simulations, error correction methods are developed, and corrected VisR τ estimates are compared with true simulated τ values to assess VisR's relevance to quantifying viscoelasticity. With regard to inertia, adding a mass term in series with the Voigt model, to achieve the MSD model, accounts for inertia due to tissue mass when ideal point force excitations are used. However, when volumetric ARF excitations are applied, the induced complex system inertia is not described by the single-degree-of-freedom MSD model, causing VisR to overestimate τ. Regarding acoustic displacement underestimation, associated deformation of ARF-induced displacement profiles further distorts VisR τ estimates. However, median error in VisR τ is reduced to approximately -10% using empirically derived error correction functions applied to simulated viscoelastic materials with viscous and elastic properties representative of tissue. The feasibility of corrected VisR imaging is then demonstrated in vivo in the rectus femoris muscle of an adult with no known neuromuscular disorders. These results suggest VisR's potential relevance to quantifying viscoelastic properties clinically.

The current gold standard for monitoring renal transplant status is invasive biopsy, which is controversial due to its associated risk for morbidity and costs. A relevant biopsy alternative could be an imaging technique that exploits the viscoelastic properties of tissue given that renal disease may result in altered viscoelastic relationships between pelvis and parenchyma. Tissue viscoelasticity is delineated by VisR ultrasound, an acoustic radiation force (ARF)-based imaging method, by fitting displacements induced by two ARF impulses to the Mass Spring Damper (MSD) model. We hypothesize that VisR measures are relevant for noninvasively distinguishing biopsied and non-biopsied allografts by assessing viscoelastic similarity between pelvis and parenchyma in renal transplant patients. VisR derived metrics: τ, relative elasticity (RE), and relative viscosity (RV) were calculated in the regions of interest (ROI): outer, center, and inner parenchyma and outer and inner pelvis. The ratios of a given VisR measure for all possible ROI combinations were compared (Wilcoxon rank sum) between biopsied and non-biopsied patients. VisR τ, RE, and RV distinguished chronic allograft nephropathy, glomerulonephritis, vascular disease, and tubular and/or interstitial scarring in biopsied versus non-biopsied allografts (p <; 0.05). These results suggest that VisR measures may be relevant metrics for noninvasively monitoring renal transplant health.

Viscoelastic Response (VisR) ultrasound is a new Acoustic Radiation Force (ARF)-based imaging method that uses two successive ARF excitations, delivered to the same region of excitation, to approximate a creep response in tissue and thereby estimate viscoelastic property. The viscoelasticity of dystrophic muscle is altered over time by ongoing necrotic, fatty, and fibrous degenerative changes. Evaluating such changes by VisR in the Golden Retriever Muscular Dystrophy (GRMD) canine model, with comparison to matched MRI and histology, is the purpose of this work. In a cross-sectional study, in vivo VisR imaging was performed on the vastus lateralis (VL) and cranial sartorius (CS) muscles in 20 dogs (n=10 control and GRMD age-matched pairs) aged 3, 6, 12, 24, or 60 months. Following VisR, T2-weighted MRI imaging was performed, and run percentage (RP) was calculated to reflect heterogeneity. Finally, muscle tissue samples were acquired by open surgical biopsy, sectioned, and stained, and percent collagen and fat were calculated from digital microscopy. In the VL, SD of VisR τ was consistently larger in GRMD versus age-matched control dogs (p=0.001, Wilcoxon two-sample test). This VisR result was consistent with higher MRI RP measures and higher histology percent collagen. Similarly in the CS, SD of VisR τ was larger in GRMD than control (p=0.001), consistent with higher MRI RP and with histology percent collagen. These results suggest that VisR measures of τ SD reflect heterogeneity due to collagen deposition in dystrophic muscles.

Viscoelastic Response (VisR) imaging is an acoustic radiation force (ARF)-based ultrasonic technique for estimating the viscoelastic properties of tissue. It has been proposed as a method for monitoring degeneration in the skeletal muscles of boys with Duchenne muscular dystrophy (DMD). DMD causes progressive inflammation, necrosis, fibrosis and fatty deposition in muscle, all of which will alter the elasticity and viscosity of the tissue. The motivation of this work is to investigate VisR's potential as method for monitoring dystrophic muscle degeneration, in vivo, in boys with DMD. In an ongoing longitudinal clinical study, muscles in the lower limbs of boys affected with DMD and age-matched healthy control boys are imaged using VisR thrice yearly for four years. A case study of serial imaging results in the Medial Gastrocnemius (GM) muscle of one boy with DMD is herein presented. Beginning at age 6.2 years, parametric VisR images of τ, or the ratio of viscosity to elasticity, show a growing region of high τ (>1.2 ms) over the span of one year. This result is consistent with expected progressive inflammation and fatty deposition early in the GM's degenerative cycle. Over the course of the next four months, the area of high τ decreases, which is in agreement with the expected onset of muscle fibrosis. Then, at age 8.3 years, small and diffusely distributed high τ regions are observed in the muscle, consistent with expected distributed fatty depositions. These results suggest that VisR, a noninvasive ultrasound imaging method, may be clinically viable for monitoring local muscular compositional and structural changes associated with dystrophic degeneration, in vivo.

Viscoelastic Response (VisR) ultrasound is an acoustic radiation force (ARF)-based imaging method for noninvasively interrogating the viscoelastic properties of tissue. ViSR ultrasound uses two successive ARF impulses delivered to a single region of excitation (ROE) and tracks the micrometer-scale induced displacements. We have previously demonstrated that tracked displacements can be fit to the mass-spring-damper model in order to measure the relaxation time constant, τ, given by the ratio of viscosity to elasticity. Because it is a ratio, we cannot determine a change in τ is due to changes in elasticity, viscosity, or both. However, elasticity and viscosity may be evaluated uniquely by VisR if considered relative to the magnitude of the forcing function. It is hypothesized that their separation enhances discrimination of viscoelastic materials in VisR ultrasound. We demonstrate that VisR is able to isolate elasticity and viscosity from τ in FEM simulated data and experimentally in a gelatin phantom with a soft inclusion.

We have previously proposed an imaging technique called Viscoelastic Response (VisR) ultrasound that uses acoustic radiation force (ARF) impulses to assess the viscoelastic properties of tissue. Using two successive ARF impulses in the same region of excitation and monitoring the induced deformation, VisR fits displacements to the mass-spring-damper mechanical model to measure the relaxation time constant, τ. In this method, ARF pulses are generated by the same transducer that is used to track motion and thus, the tracked displacements are susceptible to underestimation. Displacement underestimation introduces error into measurement of τ. It is hypothesized that by utilizing shear waves to generate displacement and monitoring tissue displacement outside the region of excitation we can better estimate axial displacements and generate τ measurements that more closely represent the material. We demonstrate displacement underestimation in, versus outside of, the ROE and the associated impact on VisR-derived τ using FEM simulations and experimentally using optical tracking in a translucent tissue-mimicking phantom.

Viscoelastic response (VisR) imaging is presented as a new acoustic radiation force (ARF)-based elastographic imaging method. Exploiting the Voigt model, VisR imaging estimates displacement in only the ARF region of excitation from one or two successive ARF impulses to estimate τ σ , the relaxation time for constant stress. Double-push VisR τ σ estimates were not statistically significantly different (p <; 0.02) from those of shearwave dispersion ultrasound vibrometry (SDUV) or monitored steady-state excitation recovery (MSSER) ultrasound in six homogeneous viscoelastic tissue mimicking phantoms with elastic moduli ranging from 3.92 to 15.34 kPa and coefficients of viscosity ranging from 0.87 to 14.06 Pa·s. In two-dimensional imaging, double-push VisR τ σ images discriminated a viscous spherical inclusion in a structured phantom with higher CNR over a larger axial range than single-push VisR or conventional acoustic radiation force impulse (ARFI) ultrasound. Finally, 2-D in vivo double-push VisR images in normal canine semitendinosus muscle were compared with spatially matched histochemistry to corroborate lower double-push VisR τ σ values in highly collagenated connective tissue than in muscle, suggesting double-push VisR's in vivo relevance to diagnostic imaging, particularly in muscle. The key advantages and disadvantages to VisR, including lack of compensation for inertial terms, are discussed.