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Imaging tissue mechanical properties has shown promise in non-invasive assessment of numerous pathologies. Researchers have successfully measured many linear tissue mechanical properties in laboratory and clinical settings. Currently, multiple complex mechanical effects such as frequency-dependence, anisotropy and nonlinearity are being investigated separately. However, a concurrent assessment of these complex effects may enable a more complete characterization of tissue biomechanics and offer improved diagnostic sensitivity. In this work we report for the first time a method to map the frequency-dependent nonlinear parameters of soft tissues on a local scale. We recently developed a nonlinear elastography model that combines strain measurements from arbitrary tissue compression with radiation-force based broadband shear wave speed measurements. Here, we extended this model to incorporate local measurements of frequency-dependent shear modulus. This combined approach provides a local frequency dependent nonlinear parameter that can be obtained with arbitrary, clinically realizable tissue compression. Initial assessments using simulations and phantoms validate the accuracy of this approach. We also observed improved contrast in nonlinearity parameter at higher frequencies. Results from ex-vivo liver experiments show 32 dB, 25 dB, dB, 34 dB, and 38 dB higher contrast in elastograms than traditional linear elasticity, elastic nonlinearity, viscosity and strain imaging methods, respectively. A lesion, artificially created by injection of glutaraldehyde into a liver specimen, showed a 59% increase in the frequency dependent nonlinear parameter and 17% increase in contrast ratio.

OBJECTIVES—: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS—: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS—: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a − 0.27 ± 0.027-m/s (−12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS—: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

The acoustic radiation force impulse (ARFI) has been widely used in transient shear wave elasticity imaging (SWEI). For SWEI based on focused ARFI, the highest image quality exists inside the focal zone due to the limitation of the depth of focus and diffraction. Consequently, the areas outside the focal zone and in the near field present poor image quality. To address the limitations of the focused beam, we introduce Bessel apodized ARFI that enhances image quality and improves the depth of focus. The objective of this study is to evaluate the feasibility of SWEI based on Bessel ARF in simulation and experiment. We report measurements of elastogram image quality and depth of field in tissue-mimicking phantoms and ex vivo liver tissue. Our results demonstrate improved depth of field, image quality, and shear wave speed (SWS) estimation accuracy using Bessel push beams. As a result, Bessel ARF enlarges the field of view of elastograms. The signal-to-noise ratio (SNR) of Bessel SWEI is improved 26% compared with focused SWEI in homogeneous phantom. The estimated SWS by Bessel SWEI is closer to the measured SWS from a clinical scanner with an error of 0.3% compared to 2.4% with a focused beam. In heterogeneous phantoms, the contrast-to-noise ratios (CNRs) of shallow and deep inclusions are improved by 8.79 and 3.33 dB, respectively, under Bessel ARF. We also compare the results between Bessel SWEI and supersonic shear imaging (SSI), and the SNR of Bessel SWEI is improved by 8.1%. Compared with SSI, Bessel SWEI shows more accurate SWS estimates in high stiffness inclusions. Finally, Bessel SWEI can generate higher quality elastograms with less energy than conventional SSI.

INTRODUCTION AND OBJECTIVES: There is a scarcity of high-fidelity, life-like, standardized and anatomically correct polymer-based kidney models for robot-assisted partial nephrectomy (RAPN) simulation training. The purpose of this technical report is to present mechanical and functional testing data as evidence for utilizing a perfused hydrogel kidney model created utilizing 3D printed injection casts for RAPN simulation and training. METHODS: Anatomically correct tumor-laden kidney models were created from 3D-printed casts designed from a patients CT scan and injected with poly-vinyl alcohol (PVA). A variety of testing methods, quantified Young’s modulus in addition to comparing the functional effects of bleeding and suturing among fresh porcine kidneys and various formulations of PVA kidneys. RESULTS: 7% PVA at 3 freeze-thaw cycles (7%−3FT) was found to be the formula that best replicates the mechanical properties of fresh porcine kidney tissue, where mean(+−SD) values of Young’s modulus of porcine tissue vs 7%−3FT samples were calculated to be 85.97(±35) kPa vs 80.97(± 9.05) kPa, 15.7(± 1.6) kPa vs 74.56(± 10) kPa and 87.46(± 2.97) kPa vs 83.4(± 0.7) kPa for unconfined compression, indentation and elastography testing respectively. No significant difference was seen in mean suture tension during renorrhaphy necessary to achieve observable hemostasis and capsular violation during a simulated perfusion at 120 mm Hg. CONCLUSIONS: This is the first study to utilize extensive material testing analyses to determine the mechanical and functional properties of a perfused, inanimate simulation platform for RAPN, fabricated using a combination of image segmentation, 3D printing and PVA casting.

Nonlinear elasticity imaging provides additional information about tissue behavior that is potentially diagnostic and avoids errors inherent in applying a linear elastic model to tissue under large strains. Nonlinear elasticity imaging is challenging to perform due to the large deformations required to obtain sufficient tissue strain to elicit nonlinear behavior. This work uses a method of axial and lateral displacement tracking to estimate local axial strain with simultaneous measurement of shear modulus at multiple compression levels. By following the change in apparent shear modulus and the stress deduced from the strain maps, we are able to accurately quantify nonlinear shear modulus. We have validated our technique with a mechanical nonlinear shear modulus measurement system. Our results demonstrate that 2D tracking provides more consistent nonlinear shear modulus estimates than those obtained by 1D (axial) tracking alone, especially where lateral motion is significant. The elastographic contrast to noise ratio in heterogeneous phantoms was 12.5%−60% higher using our method compared to 1D tracking. Our method is less susceptible to mechanical variations, with deviations in mean elastic values of 2–4% versus 5–37% for 1D tracking.

Measurement of corneal biomechanical properties can aid in predicting corneal responses to diseases and surgeries. For delineation of spatially resolved distribution of corneal elasticity, high-resolution elastography system is required. In this study, we demonstrate a high-resolution elastography system using high-frequency ultrasound for ex-vivo measurement of intraocular pressure (IOP)-dependent corneal wave speed. Tone bursts of 500 Hz vibrations were generated on the corneal surface using an electromagnetic shaker. A 35-MHz single-element transducer was used to track the resulting anti-symmetrical Lamb wave in the cornea. We acquired spatially resolved wave speed images of the cornea at IOPs of 7, 11, 15, 18, 22, and 29 mmHg. The IOP dependence of corneal wave speed is apparent from these images. Statistical analysis of measured wave speed as a function of IOP revealed a linear relation between wave speed and IOP cs = 0.37 + 0.22 × IOP, with the coefficient of determination R2 = 0.86. We also observed depth-dependent variations of wave speed in the cornea, decreasing from anterior toward posterior. This depth dependence is more pronounced at higher IOP values. This study demonstrates the potential of high-frequency ultrasound elastography in the characterization of spatially resolved corneal biomechanical properties.

Acoustic radiation force (ARF) induced Shear wave elasticity imaging (SWEI) is a noninvasive method to characterize pathological tissues. Conventionally, ARF is generated by focused beam with limited depth of focus. Supersonic shear imaging (SSI) uses multiple push-beam foci to achieve larger depth of field (DoF) elastograms. Here, we propose a SWEI method based on Bessel apodized ARF to generate larger DoF with lower energy. As a result, Bessel elastogram in gel phantom shows 19% higher contrast-to-noise ration (CNR) and 95% lower energy than SSI. Furthermore, Bessel elastogram in porcine liver shows 61% higher signal-to-noise ratio (SNR) and 56% lower energy than SSI.

Biological tissues exhibit frequency-dependent shear wave dispersion ( $c_{ph}(\omega)$ ) and absorption ( $\alpha(\omega)$ ), which carries potential diagnostic value. However, the frequency content in different elastographic excitation and tracking schemes varies, presenting systematic uncertainty and biases in quantitative shear wave imaging. We propose a maximum aposteriori probability (MAP) estimator for a single track location (STL) elastogra-phy scheme to represent shearwave propagation. The estimator accommodates wavefront and rheological modeling to arrive at material property estimates for tissue mimicking phantoms. We show that a combination of cylindrical wave (CW) geometry and fractional Kelvin-Voigt rheology demonstrate consistent estimates across acquisition parameters. We report a reduction $c_{ph}$ reconstruction bias over a range of shear wave frequencies (200–800 Hz). Results are compared with an existing 2D Fourier transform-based inversion approach and group velocity as the state-of-the-art.

Accoustic in-homogeneities within biological tissues are known to degrade image quality in elastography. Previous work has demonstrated the potential of Bessel apodized acoustic radiation force (ARF) beams in elasticity reconstructions. Bessel offers advantages, such as enlarged depth-of-field (DOF) and high diffractive immunity over conventionally focused pushes. In this study, we demonstrate Bessel ARF's ability to generate broader bandwidths for phase velocity recovery. Performance was evaluated against matched supersonic shear imaging (SSI) experiments on commercial and custom viscous phantoms. Bessel's ability to “heal”, after being disrupted by an obstacle makes it a potential candidate for developing better phase reconstruction in the presence of heterogeneity.

Imaging of tissue nonlinear elastic properties has shown potentials in providing additional information for disease diagnosis alongside traditional linear elastic properties. However, accurate local quantification of nonlinear elasticity requires precise imaging and registration of tissue strain at multiple incremental strain levels. Furthermore, it requires imaging of local stress which is measured from cumulative sum of shear wave speed squared times the differential strain. To solve this problem, here, we report measurements of shear wave speed ratio to evaluate elastic nonlinearity of tissues. In this study, we evaluate the ratio of shear wave speed (SWS) image at incremental global local strain levels to the SWS image at undeformed state of the medium. The shear wave speed ratio imaging at global strain does not require local tracking of tissue motion. On the other hand, shear wave speed ratio imaging at local strain requires local strain estimation, however, it does not require estimation of cumulative stress. Thus errors and noise associated with traditional quantitative nonlinear elasticity imaging are more compared to shear wave speed ratio imaging.

Compressional or quasi-static elastography has demonstrated the capability to detect occult cancers in a variety of tissue types, however it has a serious limitation in that the resulting elastograms are generally qualitative whereas other forms of elastography, such as shear-wave, can produce absolute measures of elasticity for histopathological classification. We address this limitation by introducing a stochastic method using an extended Kalman filter and robot-assistance to obtain quantitative elastograms which are resilient to measurement noise and system uncertainty. In this paper, the probabilistic framework is described, which utilizes many ultrasound acquisitions obtained from multiple palpations, to fuse data and uncertainty from a robotic manipulator’s joint encoders and force/torque sensor directly into the inverse reconstruction of the elastogram. Quantitative results are demonstrated over homogeneous and inclusion gelatin phantoms using a seven degree of freedom manipulator for a range of initial elasticity assumptions. Results imply resilience to poorly assumed initial conditions as all trials were within 5 kPa of the elasticity measured by a mechanical testing system. Moreover, the presence or absence of an inclusion is clear in all reconstructed elastograms even when artifacts are present in displacement fields, indicating further robustness to measurement noise. The proposed stochastic method allows fusion of data from a robot’s sensors directly into compressional elastography image reconstruction which may stabilize optimization and improve accuracy. This approach provides a mathematical framework to readily incorporate measurements from additional sensors in future applications which may extend the capabilities of compressional elastography beyond that of producing quantitative elasticity measurements.

The goal of non-linear ultrasound elastography is to characterize tissue mechanical properties under finite deformations. Existing methods produce high contrast non-linear elastograms under conditions of pure uni-axial compression, but exhibit bias errors of 10–50 % when the applied deformation deviates from the uni-axial condition. Since freehand transducer motion generally does not produce pure uniaxial compression, a motion-agnostic non-linearity estimator is desirable for clinical translation. Here we derive an expression for measurement of the Non-Linear Shear Modulus (NLSM) of tissue subject to combined shear and axial deformations. This method gives consistent nonlinear elasticity estimates irrespective of the type of applied deformation, with a reduced bias in NLSM values to 6–13 %. The method combines quasi-static strain imaging with Single-Track Location-Shear Wave Elastography (STL-SWEI) to generate local estimates of axial strain, shear strain, and Shear Wave Speed (SWS). These local values were registered and non-linear elastograms reconstructed with a novel nonlinear shear modulus estimation scheme for general deformations. Results on tissue mimicking phantoms were validated with mechanical measurements and multiphysics simulations for all deformation types with an error in NLSM of 6–13 %. Quantitative performance metrics with the new compound-motion tracking strategy reveal a 10–15 dB improvement in Signal-to-Noise Ratio (SNR) for simple shear versus pure compressive deformation for NLSM elastograms of homogeneous phantoms. Similarly, the Contrast-to-Noise Ratio (CNR) of NLSM elastograms of inclusion phantoms improved by 25–30 % for simple shear over pure uni-axial compression. Our results show that high fidelity NLSM estimates may be obtained at ~ 30 % lower strain under conditions of shear deformation as opposed axial compression. The reduction in strain required could reduce sonographer effort and improve scan safety.

Nonlinear shear modulus (NLSM) can potentially distinguish between benign and malignant breast lesions. Although studies have demonstrated the potentials of quantitative NLSM mapping techniques, the prospect of using these techniques in clinic is limited due to the challenges they pose during data acquisition. NLSM imaging requires large tissue deformation and measurement of both tissue strain and shear wave speed involving two different types of elastography techniques. It is challenging to acquire such data at multiple compression levels while maintaining the speckle correlation within a plane. Additionally, deformation induced from free-hand scanning is compound in nature, containing both compression and shear components, which is not well-modeled. In this work, we developed a freehand NLSM imaging technique that overcomes these challenges. First, we utilized a recently developed analytic model that estimates NLSM at lower levels of compound motion. Second, we developed acquisition sequences that allow rapid acquisition of strain and shear wave elastographic data.

Shear wave elasticity imaging (SWEI) has been developed to characterize the elasticity of tissue that B-mode imaging cannot. However, focused push beam has its limitation of short focal zone due to the diffraction of the wave. To improve the depth of push beam, we proposed a non-diffractive Bessel push beam induced shear wave method and used it in SWEI. In this work, a simulation study presents the superiorities of Bessel push beam over focused push beam. From the results, Bessel beam shows a larger beam depth than focused beam. Also, Bessel push beam improves the accuracy and contrast of shear wave speed images of homogeneous digital phantom. In addition, this work presents scaling factor of Bessel beam is the main parameter affecting the beam depth.

Imaging of tissue biomechanical properties like viscosity or nonlinear elasticity provide additional information about tissue composition through its contrast imaging capability. Most nonlinear elasticity imaging techniques consider group shear wave speed (SWS) changes with stress to determine the elastic nonlinearity. However, due to viscosity tissue exhibits dispersive behavior and SWS changes with frequency. Consequently, nonlinear elastic parameters change with excitation frequency. This change in nonlinear elasticity with excitation frequency is different for different tissues types. Imaging of local spectral nonlinear elastic properties could provide additional contrast compared to group shear velocity based nonlinear elastograms and help in early diagnosis.

Tissue mimicking phantoms are important components for performance testing and characterization of medical ultrasound systems. This article aims to develop a viable phantom model that can represent the acoustic properties of a fatty abdominal wall, which degrades image quality in patients who are classified as hard-to-image. Scans on a standard ultrasound phantom in the presence of the aberrating layer has revealed a marked reduction in image quality metrics. Development of a phantom surrogate that can mimic clutter and aberration similar to the fat layer can help address imaging challenges.

Single track location shear wave elasticity imaging (STL-SWEI) is immune to speckle bias, but the quality of the images is depth-dependent. We hypothesize that plane wave imaging can reduce the depth dependency of STL-SWEI. To test this hypothesis, we developed a novel technique known as plane-wave single track location shear wave elasticity imaging (pSTL-SWEI). To evaluate the pSTL-SWEI’s potential, we performed studies on phantoms and excised murine pancreatic tumors. The mean shear wave speeds (SWS) measured with STL-SWEI and pSTL-SWEI were similar. However, the elastographic signal-to-noise ratio (SNRe ) of pSTL-SWEI elastograms was noticeably higher than that produced with STL-SWEI. Specifically, we observed an improvement in SNRe ranging from 39.9%−55.1%, depending on tissue stiffness. The spatial resolution of pSTL-SWEI elastograms was 2.7%−12.1% lower than that produced with STL-SWEI. pSTL-SWEI elastograms displayed higher contrast-to-noise ratio (CNRe ) than those produced with STL-SWEI, especially when imaging was performed with low push pulse intensities and low pulse durations.

We developed an iOS-based app with a transmitter/disposable sensor and corresponding manualized intervention for children with autism spectrum disorder. The app signaled the onset of urination, time-stamped accidents for analysis, reminded parents to reinforce intervals of continence, provided a visual outlet for parents to communicate reinforcement, and afforded opportunity for timely feedback from clinicians. We compared this intervention with an intervention that uses standard behavioral treatment in a pilot randomized controlled trial of 33 children with autism spectrum disorder aged 3–6 years with urinary incontinence. Parents in both groups received initial training and four booster consultations over 3 months. Results support the feasibility of parent-mediated toilet training studies (e.g., 84% retention rate, 92% fidelity of parent-implemented intervention). Parents used the app and related technology with few difficulties or malfunctions. There were no statistically significant group differences for rate of urine accidents, toilet usage, or satisfaction at close of intervention or 3-month follow-up; however, the alarm group trended toward greater rate of skill acquisition with significantly less day-to-day intervention. Further development of alarm and related technology and future comparative studies with a greater number of participants are warranted.

The clinical use of elastography for monitoring fibrosis progression is challenged by the subtle changes in liver stiffness associated with early stage fibrosis, and the comparatively large variance of stiffness estimates provided by elastography. Single Tracking Location Shear Wave Elasticity Imaging (STL-SWEI) is an ultrasound elastography technique that was previously demonstrated to provide improved estimate precision compared to Multiple Tracking Location (MTL) SWEI. As a result of improved precision, it is reasonable to expect that STL-SWEI would provide improved ability to differentiate liver fibrosis stage compared to MTL-SWEI. However, this expectation has not been previously challenged rigorously. In this work, the performance of STL- and MTL-SWEI in the setting of a rat model of liver fibrosis is characterized and the advantages of STL-SWEI in staging fibrosis are explored. The purpose of this study is to determine what advantages, if any, arise from utilizing STL-SWEI instead of MTL-SWEI in the characterization of fibrotic liver. Thus, the ability of STL-SWEI to differentiate livers at various METAVIR fibrosis scores, for ex vivo, post-mortem measurements, is explored. In addition, we examine the effect of the common confounding factor of fluid versus solid boundary conditions in SWEI experiments. Sprague-Dawley rats are treated with carbon tetrachloride over several weeks to produce liver disease of varying severity. STL and MTL stiffness measurements were performed ex vivo and compared to the METAVIR score from histological analysis and the duration of treatment. A strong association was observed between liver stiffness and weeks of treatment with the liver toxin carbon tetrachloride. Direct comparison of STL- and MTL-SWEI measurements show no significant difference in ability to differentiate fibrosis stages based on SWEI image mean values. However, image interquartile range is greatly improved in the case of STL-SWEI imaging compared to MTL-SWEI at small beam spacings.

Nonlinear elasticity imaging provides additional information about tissue behavior that is potentially diagnostic and can lead to better tissue characterization. Nonlinear elastic properties of tissue become apparent upon application of large deformation to the medium. The majority of nonlinear elasticity estimation techniques rely on uni-axial compression. Here, we study the change in shear wave speed with the medium subjected to simple shear stress and also pure uniaxial compressive stress. Axial and lateral deformation of the tissue was tracked using quasi-static strain elastography. The local stress map is computed from cumulative sum of apparent shear modulus (measured by shear wave elastography) times the estimated differential strain. By fitting the change in local stress obtained to the estimated strain, nonlinear shear modulus is mapped. The rate of the change in local stress distribution in the medium differs with different deformations applied. However, the absolute value of nonlinear shear modulus obtained for different deformations applied were similar, thereby demonstrating the ability to give a quantitative measure of material non-linearity irrespective of subjected deformations.

In this study, a novel enuresis alarm device using a miniaturized radio frequency module and disposable sensors made with inexpensive conductive ink was used to teach toilet use for urination with three participants with severe intellectual disability (two males and one female; aged 7–15 years) in a private special education school setting. At study entry, the participants did not use the toilet for urination independently, despite prior training attempts using standard behavioral interventions. For each participant, the enuresis alarm was used as part of a manualized behavior modification program. Two of the participants progressed markedly in the acquisition of toileting skills during participation in the program, but results for the third participant were less clear. Data suggest high staff satisfaction with the device and procedure and several possible advantages over standard behavioral intervention. Thus, an enuresis alarm that comprises state-of-the-art technology may be useful for teaching toileting skills in classroom settings for some individuals with developmental disabilities.

Elastography provides tissue stiffness information that attempts to characterize the elastic properties of tissue. However, there is still limited literature comparing elastographic modalities for tissue characterization. This study focuses on two quantitative techniques using different vibration sources that have not been compared to date: crawling wave sonoelastography (CWS) and single tracking location shear wave elasticity imaging (STL-SWEI). To understand each technique’s performance, shear wave speed (SWS) was measured in homogeneous phantoms and ex vivo beef liver tissue. Then, the contrast, contrast-to-noise ratio (CNR), and lateral resolution were measured in an inclusion and two-layer phantoms. The SWS values obtained with both modalities were validated with mechanical measurements (MM) which serve as ground truth. The SWS results for the three different homogeneous phantoms (10%, 13%, and 16% gelatin concentrations) and ex vivo beef liver tissue showed good agreement between CWS, STL-SWEI, and MM as a function of frequency. For all gelatin phantoms, the maximum accuracy errors were 2.52% and 2.35% using CWS and STL-SWEI, respectively. For the ex vivo beef liver, the maximum accuracy errors were 9.40% and 7.93% using CWS and STL-SWEI, respectively. For lateral resolution, contrast, and CNR, both techniques obtained comparable measurements for vibration frequencies less than 300 Hz (CWS) and distances between the push beams ( $\Delta x$ ) between 3 mm and 5.31 mm (STL-SWEI). The results obtained in this study agree over an SWS range of 1–6 m/s. They are expected to agree in perfectly linear, homogeneous, and isotropic materials, but the SWS overlap is not guaranteed in all materials because each of the three methods have unique features.

The placenta is the critical interface between the mother and the developing fetus and is essential for survival and growth. Despite the widespread use of ultrasound imaging and Doppler in obstetrics and gynecology and the recent growth of elastographic technologies, little is known about the biomechanical (elastic shear wave) properties of the placenta and the range of normal and pathologic parameters that are present. This study uses a well-developed protocol for perfusing whole placentas, post-delivery, to maintain tissue integrity and function for hours. In this model, the placenta is living, whole and maintained within normal physiologic parameters such as flow, arterial pressure and oxygen, throughout examination by ultrasound, Doppler and shear wave elastography. The preliminary results indicate that normal placental tissue on the fetal side has shear wave speeds on the order of 2 m/s, in a range similar to those of animal livers. Some abnormalities are found outside this range, and thus, elastographic measures of the placenta may provide useful assessments related to the state of the tissue.

The physical environment of engineered tissues can influence cellular functions that are important for tissue regeneration. Thus, there is a critical need for noninvasive technologies capable of monitoring mechanical properties of engineered tissues during fabrication and development. This work investigates the feasibility of using single tracking location shear wave elasticity imaging (STL-SWEI) for quantifying the shear moduli of tissue-mimicking phantoms and engineered tissues in tissue engineering environments. Scholte surface waves were observed when STL-SWEI was performed through a fluid standoff, and confounded shear moduli estimates leading to an underestimation of moduli in regions near the fluid-tissue interface.

A challenge in the clinical application of shear wave elastography is the level of measurement variance or noise compared to clinically significant changes in shear wave speed. For instance, liver fibrosis staging is challenged by the relatively high variance of shear wave velocity estimates in comparison to the modulus difference between early (F1-F3) fibrosis stages. Recent work has shown that ultrasound speckle can be a significant source of noise in shear wave elasticity imaging (SWEI) when small tracking windows and beam spacings are employed to achieve high spatial resolution. Single tracking location (STL) methods which use multiple or shaped push beams to generate shear waves of known wavelength, and which estimate the speed of these shear waves by timing their arrival at a single tracking location, appear to be nearly immune to speckle noise. Multiple tracking location (MTL) methods are more sensitive to speckle noise, but can allow for more rapid image formation. The objective of this study is to quantify the effects of transmit beamforming parameters on STL and MTL image noise. These data will provide guidance for selection of STL or MTL in a particular imaging situation.

In ultrasound-based elastography methods, the estimation of shear wave velocity typically involves the tracking of speckle motion due to an applied force. The errors in the estimates of tissue displacement, and thus shear wave velocity, are generally attributed to electronic noise and decorrelation due to physical processes. We present our preliminary findings on another source of error, namely, speckle-induced bias in phase estimation. We find that methods that involve tracking in a single location, as opposed to multiple locations, are less sensitive to this source of error since the measurement is differential in nature and cancels out speckle-induced phase errors.

We present a novel method for ultrasound backscatter image formation wherein lateral resolution of the target is obtained by using traveling shear waves to encode the lateral position of targets in the phase of the received echo. We demonstrate that the phase modulation as a function of shear wavenumber can be expressed in terms of a Fourier transform of the lateral component of the target echogenicity. The inverse transform, obtained by measurements of the phase modulation over a range of shear wave spatial frequencies, yields the lateral scatterer distribution. Range data are recovered from time of flight as in conventional ultrasound, yielding a B-mode- like image. In contrast to conventional ultrasound imaging, where mechanical or electronic focusing is used and lateral resolution is determined by aperture size and wavelength, we demonstrate that lateral resolution using the proposed method is independent of the properties of the aperture. Lateral resolution of the target is achieved using a stationary, unfocused, single-element transducer. We present simulated images of targets of uniform and non-uniform shear modulus. Compounding for speckle reduction is demonstrated. Finally, we demonstrate image formation with an unfocused transducer in gelatin phantoms of uniform shear modulus.

Single Tracking Location (STL) Shear wave Elasticity Imaging (SWEI) is a method for detecting elastic differences between tissues. It has the advantage of intrinsic speckle bias suppression compared to Multiple Tracking Location (MTL) variants of SWEI. However, the assumption of a linear model leads to an overestimation of the shear modulus in viscoelastic media. A new reconstruction technique denoted Single Tracking Location Viscosity Estimation (STL-VE) is introduced to correct for this overestimation. This technique utilizes the same raw data generated in STL-SWEI imaging. Here, the STL-VE technique is developed by way of a Maximum Likelihood Estimation (MLE) for general viscoelastic materials. The method is then implemented for the particular case of the Kelvin-Voigt Model. Using simulation data, the STL-VE technique is demonstrated and the performance of the estimator is characterized. Finally, the STL-VE method is used to estimate the viscoelastic parameters of ex-vivo bovine liver. We find good agreement between the STL-VE results and the simulation parameters as well as between the liver shear wave data and the modeled data fit.

Acoustic Radiation Force Impulse (ARFI) imaging has been used clinically to study the dynamic response of lesions relative to their background material to focused, impulsive acoustic radiation force excitations through the generation of dynamic displacement field images. Dynamic displacement data are typically displayed as a set of parametric images, including displacement immediately after excitation, maximum displacement, time to peak displacement, and recovery time from peak displacement. To date, however, no definitive trends have been established between these parametric images and the tissue's mechanical properties. This work demonstrates that displacement magnitude, time to peak displacement, and recovery time are all inversely related to the Young's modulus of a homogeneous elastic media. Experimentally, pulse repetition frequency during displacement tracking limits stiffness resolution using the time to peak displacement parameter. The excitation pulse duration also impacts the time to peak parameter, with longer pulses reducing the inertial effects present during impulsive excitations. Material density affects tissue dynamics, but is not expected to play a significant role in biological tissues. The presence of an elastic spherical inclusion in the imaged medium significantly alters the tissue dynamics in response to impulsive, focused acoustic radiation force excitations. Times to peak displacement for excitations within and outside an elastic inclusion are still indicative of local material stiffness; however, recovery times are altered due to the reflection and transmission of shear waves at the inclusion boundaries. These shear wave interactions cause stiffer inclusions to appear to be displaced longer than the more compliant background material. The magnitude of shear waves reflected at elastic lesion boundaries is dependent on the stiffness contrast between the inclusion and the background material, and the stiffness and size of the inclusion dictate when shear wave reflections within the lesion will interfere with one another. Jitter and bias associated with the ultrasonic displacement tracking also impact the estimation of a tissue's dynamic response to acoustic radiation force excitation.

Acoustic radiation force impulse (ARFI) imaging techniques were used to monitor radiofrequency (RF) ablation of ovine cardiac tissue in vivo. Additionally, ARFI M-mode imaging methods were used to interrogate both healthy and ablated regions of myocardial tissue. Although induced cardiac lesions were not visualized well in conventional B-mode images, ARFI images of ablation procedures allowed determination of lesion location, shape, and relative size through time. The ARFI M-mode images were capable of distinguishing differences in behavior through the cardiac cycle between healthy and damaged tissue regions. As conventional sonography is often used to guide ablation catheters, ARFI imaging, which requires no additional equipment, may be a convenient modality for monitoring lesion formation in vivo.

Ultrasound Shearwave Elasticity Imaging (SWEI) is a set of methods for measuring the elastic properties of biological tissues. Since the elastic properties of tissue are known to change with disease state, the application of these methods to clinical staging of disease is an active area of research. However, the fundamental signal generation and processing techniques required to make these elastic property measurements are still being developed. Our technique, Single Track Location Acoustic Radiation Force Impulse (STL-ARFI) imaging, was developed to address spatial uncertainties in the tracking of the shearwaves. Yet, to apply the method in a clinical setting, real-time processing is required. In this work, we develop a signal processing package that provides real-time STL-ARFI elastic images using Graphic Processing Units (GPUs). This acceleration is achieved by way of a highly optimized Windowed Normalized Cross-Correlation (WNCC) algorithm achieving over 5000 frames per second of displacement estimation.

We present simulation and phantom studies demonstrating a strong correlation between errors in shear wave arrival time estimates and the lateral position of the local speckle pattern in targets with fully developed speckle. We hypothesize that the observed arrival time variations are largely due to the underlying speckle pattern, and call the effect speckle bias. Arrival time estimation is a key step in quantitative shear wave elastography, performed by tracking tissue motion via cross-correlation of RF ultrasound echoes or similar methods. Variations in scatterer strength and interference of echoes from scatterers within the tracking beam result in an echo that does not necessarily describe the average motion within the beam, but one favoring areas of constructive interference and strong scattering. A swept-receive image, formed by fixing the transmit beam and sweeping the receive aperture over the region of interest, is used to estimate the local speckle pattern. Metrics for the lateral position of the speckle are found to correlate strongly (r > 0.7) with the estimated shear wave arrival times both in simulations and in phantoms. Lateral weighting of the swept-receive pattern improved the correlation between arrival time estimates and speckle position. The simulations indicate that high RF echo correlation does not equate to an accurate shear wave arrival time estimate—a high correlation coefficient indicates that motion is being tracked with high precision, but the location tracked is uncertain within the tracking beam width. The presence of a strong on-axis speckle is seen to imply high RF correlation and low bias. The converse does not appear to be true—highly correlated RF echoes can still produce biased arrival time estimates. The shear wave arrival time bias is relatively stable with variations in shear wave amplitude and sign (−20 μm to 20 μm simulated) compared with the variation with different speckle realizations obtained along a given tracking vector. We show that the arrival time bias is weakly dependent on shear wave amplitude compared with the variation with axial position/ local speckle pattern. Apertures of f/3 to f/8 on transmit and f/2 and f/4 on receive were simulated. Arrival time error and correlation with speckle pattern are most strongly determined by the receive aperture.

Shear wave induced phase encoding (SWIPE) imaging generates ultrasound backscatter images of tissue-like elastic materials by using traveling shear waves to encode the lateral position of the scatters in the phase of the received echo. In contrast to conventional ultrasound B-scan imaging, SWIPE offers the potential advantages of image formation without beam focusing or steering from a single transducer element, lateral resolution independent of aperture size, and the potential to achieve relatively high lateral resolution with low frequency ultrasound. Here a Fourier series description of the phase modulated echo signal is developed, demonstrating that echo harmonics at multiples of the shear wave frequency reveal target k-space data at identical multiples of the shear wavenumber. Modulation transfer functions of SWIPE imaging systems are calculated for maximum shear wave acceleration and maximum shear constraints, and compared with a conventionally focused aperture. The relative signal-to-noise ratio of the SWIPE method versus a conventionally focused aperture is found through these calculations. Reconstructions of wire targets in a gelatin phantom using 1 and 3.5 MHz ultrasound and a cylindrical shear wave source are presented, generated from the fundamental and second harmonic of the shear wave modulation frequency, demonstrating weak dependence of lateral resolution with ultrasound frequency.

The thin film phantom is a new type of ultrasound resolution test object. It consists of a thin planar substrate that is acoustically matched to the surrounding media. Precisely located scatterers on the surface of the substrate generate echo signals. The patterning of scatterers on the substrate allows echogenicity to be controlled as a function of position, which enables the production of a test object with highly reproducible and controllable scattering characteristics. We show that by vibrating the substrate in a suitable manner, an echo signal may be generated that simulates bidirectional flow. We demonstrate that a vibration of low amplitude at frequency f/sub 0/ produces a Doppler spectral signal at f/sub 0/ and -f/sub 0/, within the limits of aliasing. Furthermore, by driving the film with a bandlimited noise signal, we illustrate how a velocity distribution may be simulated. A time-varying flow velocity may be simulated by varying the noise bandwidth with time. Finally, using this technique, we demonstrate a system that simulates an arterial flow pattern, including its characteristic velocity distribution in forward and reverse directions simultaneously.

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

Stereotactically placed guidewires are used for indicating the location of a nonpalpable carcinoma in breast-conserving surgery. Pathologists use the end of the embedded guidewire to guide sectioning during intraoperative margin assessment, but they do not currently have a tool to indicate the location of the guidewire end for informed sectioning. We present analysis and experimental testing of two optical methods for localizing the end of an embedded fiber-optic guidewire: the first uses irradiance emitted from the fiber to indicate the location of the guidewire end, while the second system uses the fiber optic to create a photoacoustic pulse for localization. Both systems locate the end of the guidewire within ±5 mm, which ensures that the lesion of interest is bisected during sectioning. The accuracy of the irradiance-based beacon is influenced by standard margin paints, so the photoacoustic beacon proved more useful under current tissue-handling protocols.

SWIPE is a novel method for ultrasonic image reconstruction that uses echo phase modulation induced by traveling shear waves to decipher lateral k-space image data. Our prior experimental work has demonstrated lateral resolution with SWIPE at higher than expected sidelobe levels. Here we examine the effect of the location of the mechanical excitation source used in SWIPE. Surface and internal sources were simulated using finite element modeling. The interaction of shear and surface (Rayleigh) waves was found to degrade the SWIPE point spread function when surface excitation was employed. Internal excitation was not negatively affected and yielded near-ideal results. Regions of ideal performance, simulated point spread functions, and phase non-linearity measurements for the two methods are presented. The results indicate that internal sources, e.g. acoustic radiation force, can be expected to yield high-quality SWIPE images.