Carolina Amador Carrascal

Noninvasive In vivo assessment of renal tissue elasticity during graded renal ischemia using MR elastography.

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 6 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 6 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 with controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, P = 0.3), despite histologic 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.

Phase Aberration and Attenuation Effects on Acoustic Radiation Force-Based Shear Wave Generation

Elasticity is measured by shear wave elasticity imaging (SWEI) 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, the 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 fast object-oriented C++ ultrasound simulator (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%-90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, and the resulting Pearsons 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.

Ultrasound-based shear wave evaluation in transverse isotropic tissue mimicking phantoms and muscle

Ultrasound radiation force-based methods often neglect the inherent anisotropy nature of tissue. Measurements were made in four cube-shaped phantoms composed of fibrous or fishing line material embedded in 8% and 14% gelatin concentrations and in pork tenderloin. Measurements were made at different angles relative to the transducer. For the fibrous phantom, the mean and standard deviations of the shear wave speeds for 8% and 14% gelatin along the fibers were (3.60 ± 0.03 and 4.10 ± 0.11 m/s) and across the fibers were (3.18 ± 0.12 and 3.90 ± 0.02 m/s), respectively. For the fishing line material phantom the shear wave speeds for 8% and 14% gelatin along the fibers were (2.86 ± 0.20 and 3.40 ± 0.09 m/s) and across the fibers were (2.44 ± 0.24 and 2.84 ± 0.14 m/s), respectively. For the pork muscle, the shear wave speeds along the fibers at two different locations were (3.83 ± 0.16 and 3.86 ± 0.12 m/s ) and across the fibers were (2.73 ± 0.18 and 2.70 ± 0.16 m/s), respectively. The fibrous gelatin-based phantoms and the fishing line gelatin-based phantoms exhibited anisotropy that resembles that observed in pork muscle.

Low–Energy Shockwave Therapy Improves Ischemic Kidney Microcirculation

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.

Application of shear wave imaging and shear wave dispersion ultrasound vibrometry in assessing viscoelastic properties of human thyroid: In vivo pilot study

Thyroid cancer is the fastest growing age and gender adjusted cancer in 2011 according the American Cancer Society. The majority of the clinically diagnosed thyroid nodules are benign while less than 5% represent intrathyroidal cancers. Currently, the clinical gold-standard procedure for assessing the thyroid nodules is needle biopsy, a procedure that is associated with significant financial burden as well as pain and risk for patients. Therefore, a noninvasive, affordable, and potentially widely available method to differentiate between benign and malignant thyroid nodules can play an important role in reducing the number of unnecessary biopsies. In this study, we investigate the feasibility of two acoustic radiation force elastography techniques, shear wave dispersion ultrasound vibrometry (SDUV) and comb-push ultrasound shear wave elastography (CUSE imaging), in identifying thyroid nodules (imaging) and differentiating between benign and malignant pathologies based on their elasticity and viscosity (SDUV measurements). Our preliminary results show that the measured shear elasticity and shear viscosity parameters depend on tissue type; hence, these measurements may be utilized to differentiate between healthy normal thyroid tissue, benign nodules, and malignant nodules. Further studies on a large population of patients is required to better evaluate the role of the combination of elasticity and viscosity properties of tissue in differentiating various thyroid nodules.

Robust Phase Velocity Dispersion Estimation of Viscoelastic Materials Used for Medical Applications Based on the Multiple Signal Classification Method

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

Evaluation of the nonlinear modulus in renal transplant patients using progressive and regressive compression and shear wave measurements

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Improved Shear Wave Group Velocity Estimation Method Based on Spatiotemporal Peak and Thresholding Motion Search

-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.

Low-energy extracorporeal shock wave therapy, preclinical and clinical studies

End-stage renal disease (ESRD) is an irreversible deterioration in the renal function in which the body loses its ability to maintain the fluid and metabolic balance. Transplantation is the treatment of choice for patients with ESRD. After transplantation, biopsies are performed to monitor the function of the kidney transplant over time. Due to the invasive nature of biopsies, we are investigating the potential of noninvasive shear wave based methods such as acoustoelasticity (AE) to estimate the nonlinear mechanical properties of tissues. Using AE by compressing a medium and measuring the shear wave speed at different compression levels, we can estimate the third order nonlinear coefficient, A. The goal of this study was to evaluate the feasibility of performing AE using two directions of compression and to evaluate the potential of A as an indicator of the presence of renal fibrosis in the transplanted kidney.

Evaluating arterial and plaque elasticity with shear wave elastography in an ex vivo porcine model

Quantitative ultrasound elastography is increasingly being used in the assessment of chronic liver disease. Many studies have reported ranges of liver shear wave velocity 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, ultrasound scanners, scanning protocols, and ultrasound image quality. 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 paper, 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 with 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 with conventional TTP.