Pulse-echo ultrasound attenuation tomography.

Objective.We present the first fully two-dimensional attenuation imaging technique developed for pulse-echo ultrasound systems. Unlike state-of-the-art techniques, which use line-by-line acquisitions, our method uses steered emissions to constrain attenuation values at each location with multiple crossing wave paths, essential to resolve the spatial variations of this tissue property.Approach.At every location, we compute normalized cross-correlations between the beamformed images that are obtained from emissions at different steering angles. We demonstrate that their log-amplitudes provide the changes between attenuation-induced amplitude losses undergone by the different incident waves. This allows us to formulate a linear tomographic problem, which we efficiently solve via a Tikhonov-regularized least-squares approach.Main results.The performance of our tomography technique is first validated in numerical examples and then experimentally demonstrated in custom-made tissue-mimicking phantoms with inclusions of varying size, echogenicity, and attenuation. We show that this technique is particularly good at resolving lateral variations in tissue attenuation and remains accurate in media with varying echogenicity.Significance.Based on a similar principle, this method can be easily combined with computed ultrasound tomography in echo mode for speed-of-sound imaging, paving the way towards a multi-modal ultrasound tomography framework characterizing multiple acoustic tissue properties simultaneously.

First-in-human diagnostic study of hepatic steatosis with computed ultrasound tomography in echo mode.

BACKGROUND: Non-alcoholic fatty liver disease is rapidly emerging as the leading global cause of chronic liver disease. Efficient disease management requires low-cost, non-invasive techniques for diagnosing hepatic steatosis accurately. Here, we propose quantifying liver speed of sound (SoS) with computed ultrasound tomography in echo mode (CUTE), a recently developed ultrasound imaging modality adapted to clinical pulse-echo systems. CUTE reconstructs the spatial distribution of SoS by measuring local echo phase shifts when probing tissue at varying steering angles in transmission and reception. METHODS: In this first-in-human phase II diagnostic study, we evaluated the liver of 22 healthy volunteers and 22 steatotic patients. We used conventional B-mode ultrasound images and controlled attenuation parameter (CAP) to diagnose the presence (CAP≥ 280 dB/m) or absence (CAP < 248 dB/m) of steatosis in the liver. A fully integrated convex-probe CUTE implementation was developed on the ultrasound system to estimate liver SoS. We investigated its diagnostic value via the receiver operating characteristic (ROC) analysis and correlation to CAP measurements. RESULTS: We show that liver CUTE-SoS estimates correlate strongly (r = -0.84, p = 8.27 × 10-13) with CAP values and have 90.9% (95% confidence interval: 84-100%) sensitivity and 95.5% (81-100%) specificity for differentiating between normal and steatotic livers (area under the ROC curve: 0.93-1.0). CONCLUSIONS: Our results demonstrate that liver CUTE-SoS is a promising quantitative biomarker for diagnosing liver steatosis. This is a necessary first step towards establishing CUTE as a new quantitative add-on to diagnostic ultrasound that can potentially be as versatile as conventional ultrasound imaging.

Non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation in the liver, is rapidly becoming the most common cause of chronic liver disease worldwide. Therefore, there is an urgent need to develop accurate diagnostic techniques that are inexpensive, non-invasive, and broadly available. Ultrasound imaging systems, which use sound waves to produce images of internal body structures, possess these qualities but cannot currently diagnose NAFLD accurately. Here, we propose to use a recently developed technique called computed ultrasound tomography in echo mode (CUTE). It measures the speed at which ultrasound waves propagate in tissues, a property that substantially varies with the fat content. We show that CUTE measurements allow us to accurately distinguish the livers of healthy people from those of individuals diagnosed with NAFLD. This promising finding encourages the integration of CUTE into standard ultrasound systems.

Excluding Echo Shift Noise in Real-Time Pulse-Echo Speed-of-Sound Imaging.

Computed ultrasound tomography in echo mode (CUTE) allows real-time imaging of the tissue speed of sound (SoS) using handheld ultrasound. The SoS is retrieved by inverting a forward model that relates the spatial distribution of the tissue SoS to echo shift maps detected between varying transmit and receive angles. Despite promising results, in vivo SoS maps often show artifacts due to elevated noise in echo shift maps. To minimize artifacts, we propose a technique where an individual SoS map is reconstructed for each echo shift map separately, as opposed to a single SoS map from all echo shift maps simultaneously. The final SoS map is then obtained as a weighted average over all SoS maps. Due to the partial redundancy between different angle combinations, artifacts that appear only in a subset of the individual maps can be excluded via the averaging weights. We investigate this real-time capable technique in simulations using two numerical phantoms, one with a circular inclusion and one with two layers. Our results demonstrate that the SoS maps reconstructed using the proposed technique are equivalent to the ones using simultaneous reconstruction when considering uncorrupted data but show significantly reduced artifact level for data that are corrupted by noise.

Impact of Breathing Phase, Liver Segment, and Prandial State on Ultrasound Shear Wave Speed, Shear Wave Dispersion, and Attenuation Imaging of the Liver in Healthy Volunteers.

OBJECTIVES: Measurement location and patient state can impact noninvasive liver assessment and change clinical staging in ultrasound examinations. Research into differences exists for Shear Wave Speed (SWS) and Attenuation Imaging (ATI), but not for Shear Wave Dispersion (SWD). The aim of this study is to assess the effect of breathing phase, liver lobe, and prandial state on SWS, SWD, and ATI ultrasound measurements. METHODS: Two experienced examiners performed SWS, SWD, and ATI measurements in 20 healthy volunteers using a Canon Aplio i800 system. Measurements were taken in the recommended condition (right lobe, following expiration, fasting state), as well as (a) following inspiration, (b) in the left lobe, and (c) in a nonfasting state. RESULTS: SWS and SWD measurements were strongly correlated (r = 0.805, p < 0.001). Mean SWS was 1.34 ± 0.13 m/s in the recommended measurement position and did not change significantly under any condition. Mean SWD was 10.81 ± 2.05 m/s/kHz in the standard condition and significantly increased to 12.18 ± 1.41 m/s/kHz in the left lobe. Individual SWD measurements in the left lobe also had the highest average coefficient of variation (19.68%). No significant differences were found for ATI. CONCLUSION: Breathing and prandial state did not significantly affect SWS, SWD, and ATI values. SWS and SWD measurements were strongly correlated. SWD measurements in the left lobe showed a higher individual measurement variability. Interobserver agreement was moderate to good.

Toward Speed-of-Sound Anisotropy Quantification in Muscle With Pulse-Echo Ultrasound.

The velocity of ultrasound longitudinal waves (speed of sound) is emerging as a valuable biomarker for a wide range of diseases, including musculoskeletal disorders. Muscles are fiber-rich tissues that exhibit anisotropic behavior, meaning that velocities vary with the wave-propagation direction. Therefore, quantifying anisotropy is essential to improve velocity estimates while providing a new metric related to muscle composition and architecture. For the first time, this work presents a method to estimate speed-of-sound anisotropy in transversely isotropic tissues using pulse-echo ultrasound. We assume elliptical anisotropy and consider an experimental setup with a flat reflector parallel to the linear probe, with the muscle in between. This setup allows us to measure first-arrival reflection traveltimes using multistatic operation. Unknown muscle parameters are the orientation angle of the anisotropy symmetry axis and the velocities along and across this axis. We derive analytical expressions for the nonlinear relationship between traveltimes and anisotropy parameters, including reflector inclinations. These equations are exact for homogeneous media and are useful to estimate the effective average anisotropy in muscles. To analyze the structure of this forward problem, we formulate the inversion statistically using the Bayesian framework. We demonstrate that anisotropy parameters can be uniquely constrained by combining traveltimes from different reflector inclinations. Numerical results from wide-ranging acquisition and anisotropy properties show that uncertainties in velocity estimates are substantially lower than expected velocity differences in the muscle. Thus, our approach could provide meaningful muscle anisotropy estimates in future clinical applications.

Speed of sound and shear wave speed for calf soft tissue composition and nonlinearity assessment.

BACKGROUND: The purpose of this study was threefold: (I) to study the correlation of speed-of-sound (SoS) and shear-wave-speed (SWS) ultrasound (US) in the gastrocnemius muscle, (II) to use reproducible tissue compression to characterize tissue nonlinearity effects, and (III) to compare the potential of SoS and SWS for tissue composition assessment. METHODS: Twenty gastrocnemius muscles of 10 healthy young subjects (age range, 23-34 years, two females and eight males) were prospectively examined with both clinical SWS (GE Logiq E9, in m/s) and a prototype system that measures SoS (in m/s). A reflector was positioned opposite the US probe as a timing reference for SoS, with the muscle in between. Reproducible tissue compression was applied by reducing probe-reflector distance in 5 mm steps. The Ogden hyperelastic model and the acoustoelastic theory were used to characterize SoS and SWS variations with tissue compression and extract novel metrics related to tissue nonlinearity. The body fat percentage (BF%) of the subjects was estimated using bioelectrical impedance analysis. RESULTS: A weak negative correlation was observed between SWS and SoS (r=-0.28, P=0.002). SWS showed an increasing trend with increasing tissue compression (P=0.10) while SoS values decayed nonlinearly (P<0.001). The acoustoelastic modeling showed a weak correlation for SWS (r=-0.36, P<0.001) but a very strong correlation for SoS (r=0.86, P<0.001), which was used to extract the SoS acoustoelastic parameter. SWS showed higher variability between both calves [intraclass correlation coefficient (ICC) =0.62, P=0.08] than SoS (ICC =0.91, P<0.001). Correlations with BF% were strong and positive for SWS (r=0.60, P<0.001), moderate and negative for SoS (r=-0.43, P=0.05), and moderate positive for SoS acoustoelastic parameter (r=0.48, P=0.03). CONCLUSIONS: SWS and SoS provide independent information about tissue elastic properties. SWS correlated stronger with BF% than SoS, but measurements were less reliable. SoS enabled the extraction of novel metrics related to tissue nonlinearity with potential complementary information.

Sources of Variability in Shear Wave Speed and Dispersion Quantification with Ultrasound Elastography: A Phantom Study.

There is a growing interest in quantifying shear-wave dispersion (SWD) with ultrasound shear-wave elastography (SWE). Recent studies suggest that SWD complements shear-wave speed (SWS) in diffuse liver disease diagnosis. To accurately interpret these metrics in clinical practice, we analyzed the impact of operator-dependent acquisition parameters on SWD and SWS measurements. Considered parameters were the acquisition depth, lateral position and size of the region of interest (ROI), as well as the size of the SWE acquisition box. Measurements were performed using the Canon Aplio i800 system (Canon Medical Systems, Otawara, Tochigi, Japan) and four homogeneous elasticity phantoms with certified stiffness values ranging from 3.7 to 44 kPa. In general, SWD exhibited two to three times greater variability than SWS. The acquisition depth was the main variance-contributing factor for both SWS and SWD, which decayed significantly with depth. The lateral ROI position contributed as much as the acquisition depth to the total variance in SWD. Locations close to the initial shear-wave excitation pulse were more robust to biases because of inaccurate probe-phantom coupling. The size of the ROI and acquisition box did not introduce significant variations. These results suggest that future guidelines on multiparametric elastography should account for the depth- and lateral-dependent variability of measurements.

Optimal experimental design for joint reflection-transmission ultrasound breast imaging: From ray- to wave-based methods.

Ultrasound computed tomography (USCT) is an emerging modality to image the acoustic properties of the breast tissue for cancer diagnosis. With the need of improving the diagnostic accuracy of USCT, while maintaining the cost low, recent research is mainly focused on improving (1) the reconstruction methods and (2) the acquisition systems. D-optimal sequential experimental design (D-SOED) offers a method to integrate these aspects into a common systematic framework. The transducer configuration is optimized to minimize the uncertainties in the estimated model parameters, and to reduce the time to solution by identifying redundancies in the data. This work presents a formulation to jointly optimize the experiment for transmission and reflection data and, in particular, to estimate the speed of sound and reflectivity of the tissue using either ray-based or wave-based imaging methods. Uncertainties in the parameters can be quantified by extracting properties of the posterior covariance operator, which is analytically computed by linearizing the forward problem with respect to the prior knowledge about parameters. D-SOED is first introduced by an illustrative toy example, and then applied to real data. This shows that the time to solution can be substantially reduced, without altering the final image, by selecting the most informative measurements.