Objectives Magnetic Resonance Elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors. This study tested the hypothesis that renal blood flow (RBF) is an important determinant of renal stiffness as measured by MRE. Material and Methods In six anesthetized pigs MRE studies were performed to determine cortical and medullary elasticity during acute graded decreases in RBF (by 20, 40, 60, 80, and 100% of baseline) achieved by a vascular occluder. Three sham-operated swine served as time control. Additional pigs were studied with MRE six weeks after induction of chronic unilateral RAS (n=6) or control (n=3). Kidney fibrosis was subsequently evaluated histologically by trichrome staining. Results During acute RAS the stenotic cortex stiffness decreased (from 7.4 ± 0.3 to 4.8 ± 0.6 kPa, p=0.02 vs. baseline) as RBF decreased. Furthermore, in pigs with chronic RAS (80±5.4% stenosis) in which RBF was decreased by 60±14% compared to controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, p=0.3), despite histological evidence of renal tissue fibrosis. Conclusion Hemodynamic variables modulate kidney stiffness measured by MRE and may mask the presence of fibrosis. These results suggest that kidney turgor should be considered during interpretation of elasticity assessments.

Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low-energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low-energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low-energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo A 3-week low-energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low-energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low-energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.

Currently, dynamic elastography techniques estimate the linear elastic shear modulus of different body tissues. New methods that investigate other properties of soft tissues such as anisotropy, viscosity, and shear nonlinearity would provide more information about the structure and function of the tissue and might provide a better contrast than tissue stiffness and hence provide more effective diagnostic tools for some diseases. It has previously been shown that shear wave velocity in a medium changes due to an applied stress, a phenomenon called acoustoelasticity (AE). Applying a stress to compress a medium while measuring the shear wave velocity versus strain provides data with which the third-order nonlinear shear modulus can be estimated. To evaluate the feasibility of estimating , we evaluated ten ex vivo porcine kidneys embedded in 10% porcine gelatin to mimic the case of a transplanted kidney. Under assumptions of an elastic incompressible medium for AE measurements, the shear modulus was quantified at each compression level and the applied strain was assessed by measuring the change in the thickness of the kidney cortex. Finally, was calculated by applying the AE theory. Our results demonstrated that it is possible to estimate a nonlinear shear modulus by monitoring the changes in strain and due to kidney deformation. The magnitudes of are higher when the compression is performed progressively and when using a plate attached to the transducer. Nevertheless, the values obtained for are similar to those previously reported in the literature for breast tissue.

Ultrasound shear wave elastography (SWE) is emerging as a promising imaging modality for the noninvasive evaluation of tissue mechanical properties. One of the ways to explore the viscoelasticity is through analyzing the shear wave velocity dispersion curves. To explore the dispersion, it is necessary to estimate the shear wave velocity at each frequency. An increase of the available spectrum to be used for phase velocity estimation is significant for a tissue dispersion analysis in vivo. A number of available methods suffer because the available spectrum that one can work with is limited. We present an alternative method to the classical 2-D Fourier transform (2D-FT) that uses the multiple signal classification (MUSIC) technique to provide robust estimation of the -space and phase velocity dispersion curves. We compared results from the MUSIC method with the 2D-FT technique twofold: by searching for maximum peaks and gradient-based strategy. We tested this method on digital phantom data created using finite-element methods (FEMs) in viscoelastic media as well as on the experimental phantoms used in the Radiological Society of North America Quantitative Imaging Biomarker Alliance effort for the standardization of shear wave velocity in liver fibrosis applications. In addition, we evaluated the algorithm with different levels of added noise for FEMs. The MUSIC algorithm provided dispersion curves estimation with lower errors than the conventional 2D-FT method. The MUSIC method can be used for the robust evaluation of shear wave velocity dispersion curves in viscoelastic media.

Quantitative ultrasound elastography is increasingly being used in the assessment of chronic liver disease. Many studies have reported ranges of liver shear wave velocities values for healthy individuals and patients with different stages of liver fibrosis. Nonetheless, ongoing efforts exist to stabilize quantitative ultrasound elastography measurements by assessing factors that influence tissue shear wave velocity values, such as food intake, body mass index (BMI), ultrasound scanners, scanning protocols, ultrasound image quality, etc. Time-to-peak (TTP) methods have been routinely used to measure the shear wave velocity. However, there is still a need for methods that can provide robust shear wave velocity estimation in the presence of noisy motion data. The conventional TTP algorithm is limited to searching for the maximum motion in time profiles at different spatial locations. In this study, two modified shear wave speed estimation algorithms are proposed. The first method searches for the maximum motion in both space and time (spatiotemporal peak, STP); the second method applies an amplitude filter (spatiotemporal thresholding, STTH) to select points with motion amplitude higher than a threshold for shear wave group velocity estimation. The two proposed methods (STP and STTH) showed higher precision in shear wave velocity estimates compared to TTP in phantom. Moreover, in a cohort of 14 healthy subjects STP and STTH methods improved both the shear wave velocity measurement precision and the success rate of the measurement compared to conventional TTP.

Tissue elasticity is measured by shear wave elasticity imaging methods using acoustic radiation force to create the shear waves. Phase aberration and tissue attenuation can hamper the generation of shear waves for in vivo applications. In this study effects of phase aberration and attenuation in ultrasound focusing for creating shear waves were explored. This includes the effects of phase shifts and amplitude attenuation on shear wave characteristics such as shear wave amplitude, shear wave speed, shear wave center frequency and bandwidth. Two samples of swine belly tissue were used to create phase aberration and attenuation experimentally. To explore the phase aberration and attenuation effects individually, tissue experiments were complemented with ultrasound beam simulations using FOCUS and shear wave simulations using Finite Element Model (FEM) analysis. The ultrasound frequency used to generate shear waves was varied from 3.0 to 4.5 MHz. Results The measured acoustic pressure and resulting shear wave amplitude decreased approximately 40% to 90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, the resulting Pearson’s correlation coefficients were 0.99 and 0.97. Analysis of shear wave generation with tissue samples (Phase Aberration and Attenuation case), measured phase screen (Only Phase Aberration case) and FOCUS/FEM model (Only Attenuation case) showed that tissue attenuation affected the shear wave generation more than tissue aberration. Decreasing the ultrasound frequency helped maintain a focused beam for creation of shear waves in the presence of both phase aberration and attenuation.

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Ultrasound shear wave elastography is a promising noninvasive, low cost, and clinically viable tool for liver fibrosis staging. Current shear wave imaging technologies on clinical ultrasound scanners ignore shear wave dispersion and use a single group velocity measured over the shear wave bandwidth to estimate tissue elasticity. The center frequency and bandwidth of shear waves induced by acoustic radiation force depend on the ultrasound push beam (push duration, -number, etc.) and the viscoelasticity of the medium, and therefore are different across scanners from different vendors. As a result, scanners from different vendors may give different tissue elasticity measurements within the same patient. Various methods have been proposed to evaluate shear wave dispersion to better estimate tissue viscoelasticity. A rheological model such as the Kelvin-Voigt model is typically fitted to the shear wave dispersion to solve for the elasticity and viscosity of tissue. However, these rheological models impose strong assumptions about frequency dependence of elasticity and viscosity. Here, we propose a new method called Acoustic Radiation Force Induced Creep-Recovery (ARFICR) capable of quantifying rheological model-independent measurements of elasticity and viscosity for more robust tissue health assessment. In ARFICR, the creep-recovery time signal at the focus of the push beam is used to calculate the relative elasticity and viscosity (scaled by an unknown constant) over a wide frequency range. Shear waves generated during the ARFICR measurement are also detected and used to calculate the shear wave velocity at its center frequency, which is then used to calibrate the relative elasticity and viscosity to absolute elasticity and viscosity. In this paper, finite-element method simulations and experiments in tissue mimicking phantoms are used to validate and characterize the extent of viscoelastic quantification of ARFICR. The results suggest that ARFICR can measure tissue viscoelasticity reliably. Moreover, the results showed the strong frequency dependence of viscoelastic parameters in tissue mimicking phantoms and healthy liver.