Urban, Matthew W.

Renal transplant is a long-term therapy for patients in end-stage renal disease. Renal transplant health is monitored using laboratory tests and renal biopsy. However, renal biopsy is invasive and has issues with sampling errors. Ultrasound-based shear wave elastography (SWE) is being evaluated in renal transplants to identify patients with early stages of interstitial fibrosis and inflammation. We are exploring the use of new image reconstruction approaches such as local phase velocity imaging (LPVI) to evaluate viscoelasticity in a cohort of 23 renal transplants. Additionally, from point SWE measurements we have compiled results from 97 patients and have used various machine learning approaches to differentiate patients without disease such as interstitial fibrosis, inflammation, or interstitial fibrosis with tubular atrophy (IFTA). The LPVI method provides two-dimensional maps of phase velocity and images of viscoelastic parameters after fitting to a rheological model. The machine learning approaches combine multiple elastographic parameters to provide differentiation with high sensitivity, specificity, and accuracy (∼ 85%–90%). These approaches could have substantial benefit for patients for identifying early disease in renal transplants that my precede changes in laboratory test results.

In recent years, work has been done to understand the mechanisms of Doppler ultrasound twinkling artifacts (TAs) and why they appear over kidney stones. In this work, twinkling artifacts were evaluated as a possible method of locating and characterizing kidney stones. Doppler ultrasound scanning was used to evaluate 47 stones of different types and sizes. An isolated stone study was used to understand the behavior of the TAs while varying transmit voltages. An ex vivo kidney study was conducted to determine if TAs were localized to the stones. An ex vivo randomized stone placement study was used to evaluate the robustness of detecting and locating stones. The TAs were also shown to be isolated to the stone when placed in an ex vivo kidney. The randomized stone placement study showed that this method could find all 47 used stones with only two false positives. A few limitations to this method were found with issues accurately sizing stones as well as difficulties in specificity for characterizing the stones. Further work will be done on these limitations by improving the Doppler acquisition and processing code as well as evaluating the use of TAs in human studies.

Wormlike micellar (WM) fluids exhibit a self-assembly property and viscoelastic behavior which make them a promising material for representing biological fluids, ultrasoft tissue phantoms and drug delivery carriers. Although WM biochemistry has been investigated, the mechanical properties have been rarely discussed because of the complexity of soft matter systems. Here, we demonstrate that optical coherence elastography (OCE) is capable of measuring Rayleigh wave of micellar fluids. Three solutions with concentrations of 100, 200, 300 and 400 mM, were considered in the study. Ultrasound excitation to produce Rayleigh waves was accomplished using 7.5 MHz burst excitation signals of length 4.0 ms repeated at a rate of 19 Hz. The optical coherence tomography (OCT) acquisition was set to 50 lateral positions and 4000 A-scans for each lateral position at a 76 kHz scan rate for total acquisition time of 52.6 ms. Ultrasound-based shear wave elastography, implemented on a Verasonics system, was used to obtain group and phase velocity of the shear wave in all micellar fluids as reference. Our research results demonstrated that Rayleigh wave in micellar fluids can be evaluated by OCE and mechanical properties like Young’s modulus can be assessed. A wide of concentration ranges of WM fluids would provide a more realistic model to mimic biological fluids and tissues.

Patients with chronic kidney disease (CKD) and renal transplant rejection are at high risk to develop advanced pathology including glomerular sclerosis and renal interstitial fibrosis. The elasticity of kidney tissues is associated with the disease progression and can be evaluated with ultrasound elastography. Understanding how tissue pathology changes the renal mechanical properties is crucial. Optical coherence elastography (OCE) might be a promising tool for evaluating renal tissues due to higher resolution. A phantom with 8% gelatin and 2% cellulose (50 mm) was fabricated to validate the ability of OCE to bulk materials and the results were confirmed by comparing the dataset obtained with an ultrasound-based Verasonics system as the ground truth. Excitation signals, composed with 4 cycles of a 400 Hz harmonic wave repeated at a rate of 38 Hz, were directly applied to the surface area with two directions and cortical regions of ex vivo porcine kidneys that had been cut open. Preliminary results showed that the velocity of surface wave on the cortical regions was near 1 m/s and corresponded with the result of shear waves from Verasonics system (1.2 m/s). Our study demonstrated that OCE has an ability to assess the mechanical properties of bulk materials and is a promising tool to evaluate mechanical properties of renal tissue with high resolution and sensitivity.

Local Phase Velocity Imaging (LPVI) is a novel method of shear wave elastography (SWE) analysis, which provides phase velocity images at multiple frequencies. The primary components of this method include using two acoustic radiation force (ARF) pushes near the edges of the field-of-view. Fourier analysis of the spatiotemporal data is conducted to obtain maps of the phase velocity at multiple frequencies. A robustness study was conducted to evaluate the effectiveness of LPVI in elastic and viscoelastic phantoms with different mechanical properties, ARF focal depths and F-numbers, and shear wave frequencies using a linear array transducer. The results showed effective phase velocity reconstructions for most scanning parameters in the phantoms evaluated. We evaluated mean and standard deviations of phase velocities in the different phantoms for regions-of-interest defined in the images. Issues were seen with shear wave signal being distorted from the incident push when using low F-numbers as well as issues with attenuating shear waves with higher F-numbers and deeper focal depths. Future directions of this work will be to evaluate the robustness of LPVI in inclusion phantoms as well as testing on a curved array transducer.

Shear wave elastography (SWE) is a method used in several clinical applications for assessment of soft tissue viscoelastic properties. SWE uses an acoustic radiation force (ARF) to produce laterally propagating shear waves to obtain the wave velocity. Here, we present a two-point shear wave attenuation coefficient measurement method without using a rheological model. The technique uses information related to the magnitude spectrum frequency shift of shear waves measured at only two lateral locations. We examined how the distance from the start of the ARF push and the distance between the two locations affected the attenuation coefficient estimates. We tested this method on digital phantom data created using local interaction simulation approach in viscoelastic media and on data acquired from phantom and ex vivo liver experiments. We compared the results from the two-point method with other two techniques used for assessing shear wave attenuation: the frequency-shift-based (FS) method and attenuation measuring ultrasound shearwave elastography. In comparison with the FS method, our technique does not assume that the shape parameter of the Gamma function is constant over a lateral distance. Tests conducted showed that the proposed method is feasible to provide robust attenuation estimates based on two measurement points in tissue-mimicking materials and ex vivo liver tissue.

Optoacoustic, or photoacoustic, imaging combines the penetration capabilities of ultrasound imaging with the contrast mechanism of optical absorption related to the photoacoustic effect. To enable modeling of photoacoustic measurements and imaging applications, the problem can be divided into modeling of the optical photon propagation and the resulting acoustic wave propagation. In highly scattering media such as soft tissues, Monte Carlo (MC) methods are used to evaluate photon propagation, absorption and the subsequent generation of a heat source that produces the photoacoustic effect. Acoustic wave equations are then used to model the propagation of the sound in the medium. However, if the appropriate physics could be modeled with a single tool, there would be advantages of consistency in spatial and temporal domains as well as easier integration of the optical and acoustic simulations. We propose using MC methods for optical photon propagation and for the acoustic wave propagation. The simulations are split into two stages for the optical photon propagation and the acoustic phonon propagation. We describe how the same MC framework is used to model photon propagation and acoustic phonon propagation. We will then demonstrate this new combined MC framework in models of photoacoustic problems in homogeneous and heterogeneous cases. These results will be compared with results from using k-Wave models for the acoustic wave propagation. The correspondence between k-Wave the acoustic MC model are shown to be in good agreement.

The time-of-flight approach estimates the shear elasticity in tissue mimicking elastography phantoms and in soft tissue. The time-of-flight approach is effective in elastic phantoms, but the time-of-flight approach tends to overestimate the shear elasticity in viscoelastic phantoms and in viscoelastic soft tissues. To characterize errors in estimated parameters for different values of the shear elasticity and the shear viscosity, three-dimensional (3D) shear wave simulations are evaluated for twelve different parameter combinations. The 3D acoustic radiation force is calculated for an L7-4 transducer using the fast nearfield method and the angular spectrum approach, and then, 3D shear wave propagation in a viscoelastic medium is simulated with Green's functions for a Kelvin-Voigt model. The time-of-flight method is then evaluated within a two-dimensional plane. The results show that the accuracy of the time-of-flight method depends on the values of the shear elasticity and the shear viscosity. In particular, the error in the estimated shear elasticity increases as the shear viscosity increases, where the largest errors are observed when larger values of the shear viscosity are combined with smaller values of the shear elasticity. [Work supported in part by NIH Grants DK092255, EB023051, and EB012079.]

To characterize the attenuation and dispersion behavior of shear waves in excised swine liver samples, the complex shear modulus was measured with a Rheospectris C500 + from 10 Hz to 2000 Hz. The shear wave attenuation and shear wave speed were calculated from the complex modulus measurements. A power law fit was evaluated for the shear wave attenuation, and a power law fit with and without a constant offset was evaluated for the shear wave speed. The power law closely matches the measured shear wave attenuation over most of the frequency range evaluated, although some differences are observed in several of the samples below 400 Hz. The power law without the constant offset closely matches the measured shear wave speed above 200 Hz in all measurements, where the addition of the constant offset achieves a much closer fit in all measurements that contain discrepancies below 200 Hz. The results demonstrate that shear wave attenuation in swine liver follows a power law and that a power law with a constant offset is an effective model for the shear wave speed in swine liver. [Work supported in part by NIH Grants DK092255, EB023051, and EB012079.]