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.