Reverberant shear wave elastography (R-SWE) evaluates tissue stiffness by creating a reverberant shear wave field in all directions and estimating the shear wave speed (SWS). A previous study established a linear relationship between the field's phase and the local wave number through the phase gradient (PG) method. This study introduces regularization into R-SWE to enhance the quality of the SWS maps across frequencies. Two regularization methods were analyzed: the single-channel Total Variation (TV) and the multi-frequency channel-based Total Nuclear Variation (TNV). The regularization framework involves unwrapping the phase in axial and lateral directions, calculating the l(2)-norm of the phase gradient, and proposing a minimizing cost function to address the denoising problem. Metrics were compared to PG with data from simulated and breast phantoms. Results show that regularized methods visually improved the quality of the SWS images while reducing the variability of the estimations. The contrast-to-noise ratio (CNR) was used as an overall metric. For the simulations, the average CNR values were 7.58 (PG-TNV), 2.38 (PG-TV) and 0.88 (PG). For the breast phantom, the CNR values were 4.36 (PG-TNV), 3.01 (PG-TV) and 2.39 (PG). These results suggest that regularization in R-SWE improves SWS imaging, with PG-TNV producing the best SWS maps across all frequency channels, enhancing the trade-off between variability and spatial resolution by incorporating information from multiple frequencies.

The utilization of a reverberant shear-wave field in shear-wave elastography has emerged as a promising technique for achieving robust shear-wave speed (SWS) estimation. However, many types of estimators cannot accurately measure SWS within such a complicated 3D wave field. This study introduces an advanced autocorrelation estimator based on angular integration known as the angular integral autocorrelation (AIA) approach to address this issue. The AIA approach incorporates all the autocorrelation data from various angles during measurements, resulting in enhanced robustness to both noise and imperfect distributions in SWS estimation. The effectiveness of the AIA estimator for SWS estimation is first validated using a k-Wave simulation of a stiff branching tube in a uniform background. Furthermore, the AIA estimator is applied to ultrasound elastography experiments, magnetic resonance imaging (MRI) experiments, and optical coherence tomography (OCT) studies across a range of different excitation frequencies on tissues and phantoms, including in vivo scans. The results verify the capacity of the AIA approach to enhance the accuracy of SWS estimation and the signal-to-noise ratio (SNR), even within an imperfect reverberant shear-wave field. Compared to simple autocorrelation approaches, the AIA approach can also successfully visualize and define lesions while significantly improving the estimated SWS and SNR in homogeneous background materials and providing improved elastic contrast between structures within the scans. These findings demonstrate the robustness and effectiveness of the AIA approach across a wide range of applications, including ultrasound elastography, magnetic resonance elastography (MRE), and optical coherence elastography (OCE), for accurately identifying the elastic properties of biological tissues in diverse excitation scenarios.

There are a growing set of ultrasound and viscoelastic measures that can be correlated with fat or fibrosis in the liver. We find that fat and fibrosis jointly influence important properties of the liver and can be considered as confounding cofactors within most simple measures. For example, shear wave attenuation is sensitive to the accumulation of viscous fat, but is also influenced by the degree of fibrosis, so attenuation by itself is insufficient for accurate estimation of liver fat. However, using some robust elastography techniques to assess both the shear wave phase velocity and the shear wave attenuation in a region of the liver, these measured values are found to be sufficient information for solving for both the unknown fat percent volume and the liver stiffness related to fibrosis score. A classical theory of composite viscoelastic materials is used to solve for the unknowns. Examples from human clinical studies are shown to correspond to biopsy proven grades of steatosis and fibrosis.

This study explores reverberant shear wave elastography to create accurate magnetic resonance elastograms. The reverberant elastography technique utilizes the complex wave field originating from multiple point sources or reflected from various angles and superimposed with each other. The study was conducted on a calibrated brain phantom. Results showed that reverberant elastography produced accurate elastograms with an accuracy range of 84-97% and contrast-to-noise ratios of 24 dB, compared to an accuracy range of 86-97.7% and contrast-to-noise ratios of 25 dB for the established subzone inversion method.

Non-alcoholic fatty liver disease (NAFLD) is a significant cause of diffuse liver disease, morbidity and mortality worldwide. Early and accurate diagnosis of NALFD is critical to identify patients at risk of disease progression. Liver biopsy is the current gold standard for diagnosis and prognosis. However, a non-invasive diagnostic tool is desired because of the high cost and risk of complications of tissue sampling. Medical ultrasound is a safe, inexpensive and widely available imaging tool for diagnosing NAFLD. Emerging sonographic tools to quantitatively estimate hepatic fat fraction, such as tissue sound speed estimation, are likely to improve diagnostic accuracy, precision and reproducibility compared with existing qualitative and semi-quantitative techniques. Various pulse-echo ultrasound speed of sound estimation methodologies have been investigated, and some have been recently commercialized. We review state-of-the-art in vivo speed of sound estimation techniques, including their advantages, limitations, technical sources of variability, biological confounders and existing commercial implementations. We report the expected range of hepatic speed of sound as a function of liver steatosis and fibrosis that may be encountered in clinical practice. Ongoing efforts seek to quantify sound speed measurement accuracy and precision to inform threshold development around meaningful differences in fat fraction and between sequential measurements.

Reverberant elastography provides fast and robust estimates of shear modulus; however, its reliance on multiple mechanical drivers hampers clinical utility. In this work, we hypothesize that for constrained organs such as the brain, reverberant elastography can produce accurate magnetic resonance elastograms with a single mechanical driver. To corroborate this hypothesis, we performed studies on healthy volunteers (n= 3); and a constrained calibrated brain phantom containing spherical inclusions with diameters ranging from 4-18 mm. In both studies (i.e. phantom and clinical), imaging was performed at frequencies of 50 and 70 Hz. We used the accuracy and contrast-to-noise ratio performance metrics to evaluate reverberant elastograms relative to those computed using the established subzone inversion method. Errors incurred in reverberant elastograms varied from 1.3% to 16.6% when imaging at 50 Hz and 3.1% and 16.8% when imaging at 70 Hz. In contrast, errors incurred in subzone elastograms ranged from 1.9% to 13% at 50 Hz and 3.6% to 14.9% at 70 Hz. The contrast-to-noise ratio of reverberant elastograms ranged from 63.1 to 73 dB compared to 65 to 66.2 dB for subzone elastograms. The average global brain shear modulus estimated from reverberant and subzone elastograms was 2.36 ± 0.07 kPa and 2.38 ± 0.11 kPa, respectively, when imaging at 50 Hz and 2.70 ± 0.20 kPa and 2.89 ± 0.60 kPa respectively, when imaging at 70 Hz. The results of this investigation demonstrate that reverberant elastography can produce accurate, high-quality elastograms of the brain with a single mechanical driver.

Verasonics, in partnership with Sonic Concepts (Bothell, WA, USA), has developed a turnkey platform for Ultrasound-Guided Focused Ultrasound (USgFUS) therapy with performance over a wide range of acoustic regimes. Built around the Verasonics Vantage HIFU ultrasound research system, it uses a 150 mm diameter, f1 HIFU transducer with 64 (0.5 MHz) or 128 (1.1 and 2 MHz) elements arranged in a spiral pattern that produce a highly focused field with low sidelobes over a 3D steering volume. Guidance and monitoring are provided by a coaxially mounted 128-element broadband phased array imaging transducer that can be rotated about the HIFU axis. Coupling to the subject is achieved by means of a membrane sealed water-filled cone through which degassed and temperature regulated water is circulated. The USgFUS applicator is mounted on an articulated arm that can be mechanically locked with a button actuated servo mechanism. Graphical software enables a conventional therapeutic workflow including imaging with any of several B-Mode and Doppler modalities, positioning of the applicator, focal zone exposure planning, therapy delivery, interleaved ultrasound monitoring using any supplied imaging mode or with Thermal Strain Imaging (TSI), and post-therapy imaging. This talk will describe the platform and provide examples of its capabilities using experiments in scattering phantoms and ex vivo tissues.

Introduction: The purpose of this study was to investigate the association between the mechanical properties of plantar soft tissue and diabetes status. Method: 51 (M/F: 21/30) participants with prediabetes onset (fasting blood sugar [FBS] level > 100 mg/dL), age >18 years, and no lower limb amputation were recruited after ethical approval was granted from Pontificia Universidad Catolica del Peru ethical review board. Ultrasound reverberant shear wave elastography was used to assess the soft tissue stiffness at the 1st metatarsal head (MTH), 3rd MTH, and the heel at both feet. Results: Spearman’s rank-order correlation (rho) test indicated a significant ( P < .05) positive correlations between FBS level and the plantar soft tissue shear wave speed at the 1st MTH: rho = 0.402 (@400 Hz), rho = 0.373 (@450 Hz), rho = 0.474 (@500 Hz), rho= 0.395 (@550 Hz), and rho = 0.326 (@600 Hz) in the left foot and rho = 0.364 (@450 Hz) in the right foot. Mann-Whitney U test indicated a significantly ( P < .05) higher shear wave speed in the plantar soft tissue with the following effect sizes (r) at the 1st MTH of the left foot at all tested frequencies: r = 0.297 (@450 Hz), r = 0.345 (@500 Hz), r = 0.322 (@550 Hz), and r = 0.275 (@600 Hz), and at the 1st MTH of right foot r = 0.286 (@400 Hz) in diabetes as compared with the age and body mass index matched prediabetes group. Conclusion: An association between fasting blood sugar level and the stiffness of the plantar soft tissue with higher values of shear wave speed in diabetes versus prediabetes group was observed. This indicated that the proposed approach can improve the assessment of the severity of diabetic foot complications with potential implications in patient stratification.

Elastography researchers have utilized several rheological models to characterize soft tissue viscoelasticity over the past thirty years. Due to the frequency-dependent behavior of viscoelastic parameters as well as the different techniques and frequencies employed in various studies of soft tissues, rheological models have value in standardizing disparate techniques via explicit mathematical representations. However, the important question remains: which of the several available models should be considered for widespread adoption within a theoretical framework? We address this by evaluating the performance of three well established rheological models to characterize ex vivo bovine liver tissues: the Kelvin-Voigt (KV) model as a 2-parameter model, and the standard linear solid (SLS) and Kelvin-Voigt fractional derivative (KVFD) models as 3-parameter models. The assessments were based on the analysis of time domain behavior (using stress relaxation tests) and frequency domain behavior (by measuring shear wave speed (SWS) dispersion). SWS was measured over a wide range of frequency from 1 Hz to 1 kHz using three different tests: (i) harmonic shear tests using a rheometer, (ii) reverberant shear wave (RSW) ultrasound elastography scans, and (iii) RSW optical coherence elastography scans, with each test targeting a distinct frequency range. Our results demonstrated that the KVFD model produces the only mutually consistent rendering of time and frequency domain data for liver. Furthermore, it reduces to a 2-parameter model for liver (correspondingly to a 2-parameter "spring-pot" or power-law model for SWS dispersion) and provides the most accurate predictions of the material viscoelastic behavior in time ( > 98% accuracy) and frequency ( > 96% accuracy) domains.

The reverberant shear wave (RSW) technique offers a promising framework for elastography. In this study, to characterize fibrotic fatty livers at different fibrotic stages, we employed an autocorrelation (AC) estimator within the RSW framework to evaluate shear wave speed (SWS) of viscoelastic media. To this end, we utilized both simulation and experimental approaches and excited the RSW field in a medium within each approach at the frequency of 150 Hz: (i) the finite element (FE) simulation of a RSW field in a 3D model of a whole organ fatty liver and (ii) the RSW experiments on two castoroil- in-gelatin phantoms fabricated in the lab. In the FE simulations, to represent a more realistic liver model, a thin adipose fat layer and a muscle layer were added as viscoelastic power-law materials on top of the liver model. The SWS estimation from the RSW simulation was compared with predictions from the theory of composite media for verification. For the RSW experiments on phantoms, the SWS estimations were compared with the SWS results obtained from performing the stress relaxation test as an independent modality. The simulation results showed that the RSW-based AC estimator provides good estimates of SWS, within >90% accuracy compared with theory. Also, the RSW estimator results from the phantom experiments at different background stiffness levels provided some experimental support for the utility of the RSW estimator. These results demonstrated that the AC estimator is sensitive to the changes in viscoelastic properties of viscoelastic media.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

The quantification of liver fat as a diagnostic assessment of steatosis remains an important priority for non-invasive imaging systems. We derive a framework in which the unknown fat volume percentage can be estimated from a pair of ultrasound measurements. The precise estimation of ultrasound speed of sound and attenuation within the liver is found to be sufficient for estimating fat volume assuming a classic model of the properties of a composite elastic material. In this model, steatosis is represented as a random dispersion of spherical fat vacuoles with acoustic properties similar to those of edible oils. Using values of speed of sound and attenuation from the literature in which normal and steatotic livers were studied near 3.5 MHz, we describe agreement of the new estimation method with independent measures of fat. This framework holds the potential for translation to clinical scanners with which the two ultrasound measurements can be made and used for improved quantitative assessment of steatosis.

S FROM THE 2021 INTERNATIONAL SYMPOSIUM ON ULTRASONIC IMAGING AND TISSUE CHARACTERIZATION Virtual Conference 02 to 04 June 2021 https://doi.org/10.1177/01617346211031090 Ultrasonic Imaging 2021, Vol. 43(4) 187 –233 © The Author(s) 2021 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/01617346211031090 journals.sagepub.com/home/uix Abstracts In vivo Lag-one Coherence Measurements Using Matrix Arrays Rifat Ahmed1, Nick Bottenus2, James Long1, David Bradway1, and Gregg Trahey1 1Dept. of Biomed. Eng., Duke University, NC, USA and 2Dept. of Mech. Eng., University of Colorado Boulder, CO, USA, rifat.ahmed@duke.edu Objectives: Diffuse reverberation is a significant source of image degradation in abdominal ultrasound. Clutter induced by reverberation is often considered to be spatially incoherent. The nearest element correlation of backscatter signals provides a robust measure of such incoherent clutter [1]. We recently presented Lag-one Spatial Coherence Adaptive Normalization (LoSCAN) [2], an image formation technique that adaptively compensates for the SNR loss due to incoherent clutter. Here, we present in vivo LoSCAN images obtained with a 1024-element matrix array and explore the benefits of 2D clutter reduction. Methods: We developed a 2D LoSCAN framework applicable to matrix arrays. We validated this framework using Field II-simulated cyst phantoms of varying native contrasts and channel SNR, with a modeled 64x64 symmetric 2D array. Using these simulated data, we studied the impact of partially correlated noise (PCN) with controlled spatial correlation lengths (1λ to 3λ). Sub-aperture beamforming and a short-lag version of LoSCAN were explored as strategies to circumvent the PCN-induced contrast loss. We also acquired experimental data using a custom 64x16 2D array connected to a 1024-channel Verasonics system. We acquired fundamental and harmonic channel data from the liver of two healthy volunteers and performed 2D spatial coherencebased clutter analysis. Results: Compared to B-mode imaging, matrix LoSCAN preserved the native contrast and improved the lesion detectability, measured with the generalized contrast-to-noise ratio (gCNR), over a wider range of channel SNR. In vivo observations demonstrated the anisotropy of reverberation-noise correlation length. Matrix LoSCAN also improved the gCNR of abdominal anechoic targets from 0.92 to 0.97 in fundamental images and from 0.91 to 0.97 in harmonic images. Conclusions: Matrix LoSCAN effectively suppressed the incoherent clutter in abdominal ultrasound images. In vivo examples demonstrated the advantages of multi-dimensional clutter analysis. [1] Long et al., IEEE-TUFFC, 2018 [2] Long et al., IEEE-TUFFC, 202

A framework is developed for estimating the volume fraction of fat in steatotic livers from viscoelastic measures of shear wave speed and attenuation. These measures are emerging on clinical ultrasound systems' elastography options so this approach can become widely available for assessing and monitoring steatosis. The framework assumes a distribution of fat vesicles as spherical inhomogeneities within the liver and uses a composite rheological model (Christensen 1969J. Mech. Phys. Solids1723-41) to determine the shear modulus as a function of increasing volume of fat within the liver. We show that accurate measurements of shear wave speed and attenuation provide the necessary and sufficient information to solve for the unknown fat volume and the underlying liver stiffness. Extension of the framework to compression wave measurements is also possible. Data from viscoelastic phantoms, human liver studies, and steatotic animal livers are shown to provide reasonable estimates of the volume fraction of fat.

There are a variety of approaches used to create elastography images. Techniques based on shear wave propagation have received significant attention. However, there remain some limitations and problems due to shear wave reflections, limited penetration in highly viscous media, requirements for prior knowledge of wave propagation direction, and complicated propagation in layers where surface acoustic waves and guided waves are dominant. To overcome these issues, reverberant shear wave elastography (RSWE) was proposed as an alternative method which applies the concept of a narrow-band diffuse field of shear waves within the tissue. Since 2017, the RSWE approach has been implemented in ultrasound (US) and optical coherence tomography (OCT). Specifically, this approach has been implemented in these imaging modalities because they are similar in image formation principles and both share several approaches to estimate the biomechanical properties in tissues. Moreover, they cover different spatial-scale and penetration depth characteristics. RSWE has shown promising results in the elastic and viscoelastic characterization of multiple tissues including liver, cornea, and breast. This review summarizes the 4-year progress of the RSWE method in US and OCT. Theoretical derivations, numerical simulations, and applications in ex vivo and in vivo tissues are shown. Finally, we emphasize the current challenges of RSWE in terms of excitation methods and estimation of biomechanical parameters for tissue-specific cases and discuss future pathways for the in vivo and in situ clinical implementations.

Reverberant shear wave fields are produced when multiple sources and multiple reflections establish a complex three-dimensional wave field within an organ. The expected values are assumed to be isotropic across all directions and the autocorrelation functions for velocity are expressed in terms of spherical Bessel functions. These results provide the basis for adroit implementations of elastography from imaging systems that can map out the internal velocity or displacement of tissues during reverberant field excitations. By examining the phase distribution of the reverberant field, additional estimators can be derived. In particular, we demonstrate that the reverberantphase gradientis shown to be proportional to the local value of wavenumber. This phase estimator is less sensitive to imperfections in the reverberant field distribution and requires a smaller support window, relative to earlier estimators based on autocorrelation. Applications are shown in simulations, phantoms, andin vivoliver.

Plantar soft tissue stiffness provides relevant information on biomechanical characteristics of the foot. Therefore, appropriate monitoring of foot elasticity could be useful for diagnosis, treatment or health care of people with complex pathologies such as a diabetic foot. In this work, the reliability of reverberant shear wave elastography (RSWE) applied to plantar soft tissue was investigated. Shear wave speed (SWS) measurements were estimated at the plantar soft tissue at the first metatarsal head, the third metatarsal head and the heel from both feet in five healthy volunteers. Experiments were repeated for a test-retest analysis with and without the use of gel pad using a mechanical excitation frequency range between 400 and 600 Hz. Statistical analysis was performed to evaluate the reliability of the SWS estimations. In addition, the results were compared against those obtained with a commercially available shear wave-based elastography technique, supersonic imaging (SSI). The results indicate a low coefficient of variation for test-retest experiments with gel pad (median: 5.59%) and without gel pad (median: 5.83%). Additionally, the values of the SWS measurements increase at higher frequencies (median values: 2.11 m/s at 400 Hz, 2.16 m/s at 450 Hz, 2.24 m/s at 500 Hz, 2.21 m/s at 550 Hz and 2.31 m/s at 600 Hz), consistent with previous reports at lower frequencies. The SWSs at the plantar soft tissue at the first metatarsal head, third metatarsal head and heel were found be significantly (p<0.05) different, with median values of 2.42, 2.16 and 2.03 m/s, respectively which indicates the ability of the method to differentiate between shear wave speeds at different anatomical locations. The results indicated better elastographic signal-to-noise ratios with RSWE compared to SSI because of the artifacts presented in the SWS generation. These preliminary results indicate that the RSWE approach can be used to estimate the plantar soft tissue elasticity, which may have great potential to better evaluate changes in biomechanical characteristics of the foot.

Although muscle echo intensity (EI) has been proposed as a biomarker for the diagnosis of frailty, so far no studies have explored it ́s diagnostic performance. Fractal dimension (FD) can play an important role for modeling different organs in ultrasound studies, and since muscles have fractal properties, it could help to characterize muscle further with imaging. We assessed muscle EI and FD from muscle ultrasound to determine the relationship between the two variables, and their diagnostic capability to identify frailty phenotype. A retrospective interpretation of ultrasound scans from a previous cohort was performed. The sample included healthy participants <60 years old, and participants ≥60 divided into robust, pre-frail, and frail groups according to Fried frailty criteria. A region of interest of the rectus femoris from the ultrasound scan was segmented, and histogram function was applied to obtain EI. Images were also processed using twodimensional box-counting techniques to calculate FD. Statistical analyses were performed with diagnostic performance tests. A hundred and two participants (mean age 63±16, 57 men) were evaluated. The main results showed that muscle FD correlated with EI (r = 0.38, P <0.01) and showed different patterns according to frailty phenotype. The diagnostic performance for EI to categorize frailty as present or absent was good (AUC of 0.69 95%CI 0.59-0.78, P = 0.001). However, the diagnostic performance for the combination of both EI and FD resulted in no improvement of the diagnostic performance (AUC of 0.58 A.U., 95%CI: 0.46-0.68, P = 0.18). In conclusion, we determined that EI was useful to identify individuals at risk of frailty, and while FD did not improve the detection of frailty, it was able to characterize the individuals further by reflecting changes in the muscle that likely reflects the known frailty-related muscle dysfunction secondary to degeneration of the muscle architecture. This allowed us to dichotomize our sample in the most appropriate way for the identification of frailty and improve EI as a possible diagnostic tool for frailty phenotype. Ultrasonic attenuation as a biomarker for liver steatosis: an AIUM/QIBA perspective K. Nam1, M. Alexander1, S. Audiere1, C. X. Baiu1, J. Bamber1, T. Bigelow1, P. Carson1, A. Chauhan1, S. Chen1, Y. Chen1, G. Cloutier1, C. De Korte1, A. Engel1, T. Erpelding1, R. Esquivel-Sirvent1, B. Fowlkes1, J. Gao1, J. Gay1, Z. Hah1, T. Hall1, J-P. Henry1, A. Lex1, T. Liu1, T. Lynch1, J. Mamou1, R. Managuli1, L. Mankowski-Gettle1, S. McAleavy1, G. McLauglin1, A. Milkowski1, G. Ng1, N. Obuchowski1, J. Ormachea1, S. Ouhda1, M. Robbin1, B. Rogozinski1, J. Rubin1, L. Sandrin1, A. Sanyal1, P. Sidhu1, K. Thomenius1, M. Thornton1, X. Wang1, K. Wear1, J. Zagzebski1, A. Han2, R. Lavarello2, T. Tuthill2, T. Pierce3, S. Rosenzweig3, D. Fetzer4, T. Stiles4, I. Rosado-Mendez5, M. Wang5, A. Samir5, R. Barr6, G. Ferraioli6, A. Ozturk6, V. Kumar6* The high prevalence of Non-alcoholic fatty liver disease (NAFLD), about 25% of the global population, has necessitated quantitative imaging tools [1]. NAFLD is characterized by steatosis, excessive deposition of fat in the liver, commonly referred to as a fatty liver disease. Liver biopsy is the clinical standard for diagnosing NAFLD and grading steatosis. However, the biopsy is limited by cost, high sampling variability, and procedureassociated morbidity restricting repetitive use. Although ultrasound is the first line of imaging modality for diagnosing NAFLD, the current practice is based on sonographic hepatorenal index leveraging the increased liver brightness due to fat deposition in comparison to the kidney. The practice suffers from user subjectivity, non-quantitative, and low sensitivity in the detection of mild steatosis, 60.9%-65% [2, 3]. Ultrasonic attenuation is the loss of ultrasound energy as the acoustic wave propagates in soft tissue. Estimation of local ultrasonic attenuation provides information regarding the underlying nature of the soft tissue. Fatty tissue is known to be more attenuative than normal liver tissue; thus, a local attenuation estimate can act as a surrogate marker for liver steatosis. With the maturity of technology, the stage for attenuation to become clinically adopted has been set. Ultrasound vendors are following suit and most of the ultrasound vendors have already introduced attenuation estimation techniques in their flagship models. However, before the wide clinical adoption of attenuation as a biomarker for fatty liver disease, there is a need to standardize attenuation measurement, understand sources of bias and variance, improve data quality, and reach a consensus on reporting attenuation values. The AIUM/QIBA Pulse-Echo Quantitative Ultrasound (PEQUS) attenuation workgroup is seeking to provide guidance on key attenuation parameters such as transmit center frequency, region of interest, depth, and frame rate. In addition, good practices guidance for acquiring attenuation estimates, displaying results, and calibrating systems will be provided. Finally, the attenuation variability within a system, between systems, and between operators will be documented using customized, well-characterized phantoms. 1. Younossi, Z.M., et al., Global epidemiology of non-alcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016. 64(1): p. 73-84. 2. Dasarathy, S., et al., Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. Journal of hepatology, 2009. 51(6): p. 1061-1067. 3. van Werven, J.R., et al., Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. Radiology, 2010. 256(1): p. 159-168. Ultrasonic parametric imaging of brain tissue using the backscatter difference technique Will R. Newman1, Cecille Labuda2, Claudia K. M. Chambliss2 and Brent K. Hoffmeister1, Rhodes College Department of Physics, Memphis, TN 38112, Department of Physics and Astronomy, University of Mississippi, University, MS 38677. newwr-21@rhodes.edu Background & Objective: Transcranial ultrasonic backscatter can, in principle, be used to analyze brain tissue properties non-invasively. The main challenge involves errors associated with ultrasonic attenuation and distortion of the ultrasonic wave front by the skull. A newly developed backscatter difference technique may be relatively insensitive to these errors. The goal of this study was to generate parametric images of brain tissue based on three backscatter difference parameters called the normalized mean, slope and intercept of the backscatter difference (nMBD, nSBD and nIBD respectively). Each parameter measures an aspect of a power spectrum derived from the spectral difference between two portions of the same backscatter signal. Methods: Tissue specimens used in the study were 1 cm thick slices of preserved sheep brain prepared from the coronal, sagittal and transverse anatomic planes. Pulse-echo measurements were performed in vitro using broadband, single-element transducers with center frequencies of 3.5, 5.0, 7.5 and 10 MHz. The transducers were mechanically scanned with a step size equal to one-half of a beam diameter to acquire data from all locations on each slice. Values of nMBD, nSBD and nIBD measured at each location were used to produce parametric images of the brain specimens. Results: Structures visible in the parametric images were consistent with anatomic features of the brain. Depending on the tissue slice and transducer frequency, measured mean values ranged between -0.134 and 2.04 dB⸱μs-1 for nMBD, -0.245 and 1.523 dB⸱μs-1⸱MHz-1 for nSBD, and 0.425 and 2.152 dB⸱μs-1 for nIBD. Conclusions: These results lay the groundwork for transcranial ultrasonic backscatter measurements of the brain by providing baseline measurements of nMBD, nSBD and nIBD for brain tissue. Future work will compare these results to measurements made through skull bone. Quantitative Viscoelastic Response (QVisR) ultrasound in mechanically heterogeneous inclusions Joseph Richardson1, Caterina Gallippi2, 1Electrical and Computer Engineering, North Carolina State University, 2Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, jbricha5@ncsu.edu Background: Point-wise, on-axis estimation of viscoelasticity would allow a finer resolution and relaxed region homogeneity assumptions when compared with shear wave based elastography methods. QVisR was previously validated in silico with mechanically homogeneous, isotropic, linearly viscoelastic materials. This work extends QVisR to mechanically heterogeneous materials, in silico. Methods: We simulated viscoelastic materials with spherical inclusions subject to an applied double-push VisR sequence with ultrasonic tracking using a combination of Field II and Ansys LS-DYNA. A Siemens VF73 transducer was modeled to push and track at focal depths from 15-35mm in steps of 5mm. The double-push VisR sequence was applied to 16 material combinations where the background shear elastic and viscous moduli were fixed (8.7kPa and 0.78Pa.s) while the inclusion shear elastic and viscous moduli varied (5.18-12.22 kPa, 0.003-1.30 Pa.s). The inclusion was shifted laterally in 4 increments (0, 2.5, 4, 7mm) to interrogate the effects of the lateral inclusion boundary on the applied force distribution. The resulting FEM nodal displacements were translated to 5 randomly initialized scatterer fields and then ultrasonically tracked. White Gaussian electronic noise (20-50dB SNR) was added to the simulated RF lines before tracking with normalized cross correlation. In total, 11.2 million tracked displacement time series were simulated, added to the previous QVisR homogeneous material dataset, and then split into train/validation/test sets for machine learning model training and evaluation.

Reverberant shear wave elastography (RSWE) has become a promising approach to quantifying soft tissues' viscoelastic properties by the propagating shear wave speed (SWS) estimation based on the particle velocity autocorrelation. In this work, three different practical settings were evaluated for the SWS estimation by numerical simulations of an isotropic, homogenous, and elastic medium: first, the 2D representation of the particle velocity, second, the spatial autocorrelation computation, and third, the selection of the curve fitting domain. We conclude that the 2D autocorrelation function using the Wiener-Khinchin theorem provides up to 127 times faster results than traditional autocorrelation methods. Additionally, we state that extracting the magnitude and phase from the Fourier transform of the temporal domain, applying the 2D-autocorrelation on a mobile square window sized at least two wavelengths, and fitting the monotonically decreasing part of the autocorrelation profile's central lobe results in more accurate (13.2% of bias) and precise (5.3% of CV) estimations than other practical settings.Clinical relevance- Affections in soft tissues' biomechanical properties are related to pathologies, such as tumor cancer, muscular degenerative diseases, or fibrosis. These changes are quantified by the SWS and its derived viscoelastic parameters. RSWE is a promising approach for their characterization. In this work, we evaluated alternative elections of practical settings within the methodology. Numerical simulations indicate they lead to faster and more reliable local SWS estimations than conventional settings.

From the development of x-ray imaging in the late 19th century, the field of medical imaging developed an impressive array of modalities. These can measure and image a variety of physical parameters from absorption coefficients to spin-spin relaxations. However, throughout most of the 20th century, the intrinsic biomechanical properties of tissues remained hidden from conventional radiology. This changed around 1990 when it was demonstrated that medical ultrasound systems with their fast pulse repetition rate and high sensitivity to motion could create images related to the stiffness of tissues and their shear wave properties. From there, vigorous development efforts towards imaging the elastic properties of tissues were launched across different modalities. These progressed from the research phase, through implementation on clinical scanners, through extensive clinical trials of selected diagnostic tasks, to government approvals, payer approvals, international standards statements, and into routine clinical practice around the globe. This review covers highlights of some major topics of the technical and clinical developments over the last 30 years with brief pointers to some of the remaining issues for the next decade of development.