山口 匡

Abstract This study investigates the dependence of the translational velocity of lipid-coated microbubbles in an ultrasound field on the viscosity of the surrounding Newtonian fluid. Plane burst waves with a center frequency of 7.34 MHz were used to uniformly drive microbubbles with a radius of 1.4 ± 0.3 m (mean ± standard deviation) in a flow channel. Bubbles were detected using the Doppler method using pulse waves with a center frequency of 5.2 MHz, and the velocities of individual bubbles were analyzed by tracking them in consecutive images. Examinations were conducted at various viscosities from 1 to 3 mPa∙s. The experimentally determined velocity–viscosity relationship qualitatively agreed with numerical simulations. This was written as a power-law dependence and used as a calibration curve to evaluate the local viscosity coefficient for the trajectories of individual bubbles. We succeeded in demonstrating viscosity imaging by multiplying the obtained viscosity coefficient with the bubble trajectories, convoluted with the point spread function of ultrasound imaging.

Abstract We conducted a fundamental study to elucidate the relationship between acoustic and electrical properties in the context of liver steatosis. The speed of sound, attenuation coefficient, conductivity, and relative permittivity were measured in rat livers with varying degrees of fat deposition. Fat deposition result in a decrease in the speed of sound, an increase in the attenuation coefficient, and reductions in conductivity and relative permittivity. However, no linear correlation was observed between these properties and fat content or droplet size individually. However, a notable correlation between changes in acoustic and electrical properties was identified when the structural and organizational effects of fat were considered in combination. Especially, attenuation changes were found to correlate with corresponding changes in electrical properties. These findings underscore the importance of comprehensively considering structural factors, such as fat droplet size and distribution, to better understand the physical mechanisms underlying the relationship between acoustic and electrical properties.

Hemorheological properties, such as erythrocyte aggregation can be assessed by ultrasonic backscatter coefficient analysis. In this study, a data-acquisition sequence with dual-frequency (dual-f) excitation was proposed to expand the ultrasonic frequency bandwidth with high-frame-rate imaging. The approach was experimentally validated using ex vivo porcine blood measurements and in vivo human imaging. The center frequency of the excitation wave was alternated between 7.8 (f1) and 12.5 (f2) MHz in the frequency spectral analysis using the reference phantom method. The frequency spectra revealed that the dual-f sequence achieved a bandwidth of 4.5-15 MHz at -20 dB, almost equivalent to those achieved with conventional single-frequency excitation (5.0-15 MHz) with a short-duration wave at 10 MHz (mono-f) in reference media with the sufficient condition of signal-to-noise ratio. The aggregation and disaggregation states of porcine blood suspended in high-molecular-weight dextran were determined by the isotropic diameter and packing factor using the structure factor size estimator. The discrimination performance of the dual-f approach increased, owing to the broadband frequency responses, in contrast with the limited performance of mono-f due to a low signal-to-noise ratio. This approach incorporating dual-f sequence is beneficial for obtaining robustly frequency spectra of hemorheological properties from in vivo scenarios.

Abstract Purpose Early detection and quantitative evaluation of liver steatosis are crucial. Therefore, this study investigated a method for classifying ultrasound images to fatty liver grades based on echo-envelope statistics (ES) and convolutional neural network (CNN) analyses. Methods Three fatty liver grades, i.e., normal, mild, and moderate-to-severe, were defined using the thresholds of the magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). There were 10 cases of each grade, totaling 30 cases. To visualize the texture information affected by the deposition of fat droplets within the liver, the maps of first- and fourth-order moments and the heat maps formed from both moments were employed as parametric images derived from the ES. Several dozen to hundreds of regions of interest (ROIs) were extracted from the liver region in each parametric image. A total of 7680 ROIs were utilized for the transfer learning of a pretrained VGG-16 and classified using the transfer-learned VGG-16. Results The classification accuracies of the ROIs in all types of the parametric images were approximately 46%. The fatty liver grade for each case was determined by hard voting on the classified ROIs within the case. In the case of the fourth-order moment maps, the classification accuracy of the cases through hard voting mostly increased to approximately 63%. Conclusions The formation of parametric images derived from the ES and the CNN classification of the parametric images were proposed for the quantitative diagnosis of liver steatosis. In more than 60% of the cases, the fatty liver grade could be estimated solely using ultrasound images.

The objective of this work is to address the need for versatile and effective tissue characterization in abdominal ultrasound diagnosis using a simpler system. We evaluated the backscattering coefficient (BSC) of several tissue-mimicking phantoms utilizing three different ultrasonic probes: a single-element transducer, a linear array probe for clinical use, and a laboratory-made annular array probe. The single-element transducer, commonly used in developing fundamental BSC evaluation methods, served as a benchmark. The linear array probe provided a clinical comparison, while the annular array probe was tested for its potential in high-frequency and high-resolution ultrasonic observations. Our findings demonstrate that the annular array probe meets clinical demands by providing accurate BSC measurements, showcasing its capability for high-frequency and high-resolution imaging with a simpler, more versatile system.

Abstract Analysis of the envelope statistics of ultrasound echo signals contributes to quantitative tissue characterization in medical ultrasound. Many probability distribution model functions have been studied, and the model function that should be used for tissue characterization depends on the type of disease, even in the same organ. Thus, an appropriate model selection is important for an accurate diagnosis. In this study, we aimed to select a model using threshold processing for modeling errors instead of a simple selection by minimizing the modeling error. For this purpose, we compared several indicators of modeling errors using random number simulations, ultrasonic simulation, and phantom experiment. The results validated that the Mahalanobis distance of moments is an appropriate indicator because it enables the use of a constant threshold value, regardless of the type of model function and data length.

Abstract The double–Nakagami (DN) model provides a method for analyzing the amplitude envelope statistics of quantitative ultrasound (QUS). In this study, the relationship between the sound field characteristics and the robustness of QUS evaluation was evaluated using five HF linear array probes and tissue-mimicking phantoms. Compound plane-wave imaging (CPWI) was used to acquire echo data. Five phantoms containing two types of scatterers were used to mimic fatty liver tissue. After clarifying the relationship between the sound field characteristics of the probes and QUS parameters, DN QUS parameters in 10 rat livers with different lipidification were evaluated using one HF linear array probe. For both phantom and in situ liver analyses, correlations between fat content and multiple QUS parameters were confirmed, suggesting that the combination of CPWI using a HF linear array probe with the DN model is a robust method for quantifying fatty liver and has potential clinical diagnostic applications.

Abstract Backscatter coefficient analysis methods for biological tissues have been clinically applied but assume a homogeneous scattering medium. In addition, there are few examples of actual measurement studies in the HF band, and the consistency with theory has not been sufficiently confirmed. In this paper, the effect of correlations among scatterer positions on backscattering was investigated by performing experiments on inhomogeneous media having two types of scattering source with different structural and acoustic properties. In the echo data of phantoms containing two types of scatterer acquired by multiple sensors, the power and frequency dependence of the backscatter coefficient were different from theoretical calculations due to the interference effects of each scatterer. The effect of interference between the two types of scatterer was confirmed to be particularly strong for echoes acquired by the sensor at high intensity and HF, or for a higher number density of strong scatterers.

OBJECTIVE: Hepatic fibrosis has recently been evaluated using ultrasonography or magnetic resonance elastography. Although the shear wave velocity (SWV) obtained using point shear wave elastography (pSWE) provides a valuable measure of fibrosis, underlying steatosis may affect its measurement. METHODS: Using hepatic fibrosis samples, this study evaluated the effect of steatosis on the shear wave velocity of pSWE (Vs) and viscoelastic properties (assessed by dynamic mechanical analysis) of rat liver. Fifty rats with various grades of steatosis and fibrosis underwent open abdominal in vivo Vs measurements using a commercial ultrasound scanner. The mechanical properties of hepatic tissue were also characterized under ex vivo conditions using dynamic mechanical analysis and the Zener model of viscoelasticity. RESULTS: Fibrosis and steatosis progression influenced Vs and elasticity. The SWV computed using the Zener model and Vs showed a substantial correlation (r > 0.8). Fibrosis progression increased SWV. Steatosis was also related to SWV. Steatosis progression obscured the SWV change associated with fibrosis progression. CONCLUSION: We conclude that steatosis progression affects the evaluation of fibrosis progression. This finding could aid discrimination of non-alcoholic steatohepatitis from non-alcoholic fatty liver disease using SWV.

We propose burst-wave-aided, contrast-enhanced, active Doppler ultrasonography for visualizing lymph vessels. This technique forces ultrasound contrast agents (UCAs) to move using the acoustic radiation force induced by burst waves with low amplitude while suppressing their destruction. Using a flow phantom, we measured the average, decrease rate of echo intensity [i.e., pulse intensity integral (PII)], and the velocity of individual contrast agents, which directly affects the performance of imaging and tracking contrast agents under stationary flow conditions. Comparison with pulse-inversion Doppler without exposure to the burst wave demonstrated that the velocity of the contrast agents could be enhanced up to several tens of millimeters per second by the effect of the burst wave, maximizing the echo intensity extracted by a clutter filter. The contrast ratio (CR), defined as the ratio of the contrast echo to the phantom echo outside the channel, did not change appreciably, even when the lower cut-off velocity of the clutter filter was increased up to 10 mm/s. This implies a better robustness against the motion of the tissue. In addition, the performance for detecting contrast agents (i.e., echo intensity) was superior or similar to that of pulse-inversion Doppler, even in undesirable conditions where the flow had a velocity component in the opposite direction to that of the acoustic radiation force. The echo intensity was lower or the same as that in pulse-inversion Doppler, demonstrating the potential for suppressing the destruction of contrast agents and enabling long-term observations. From these results, we expect that the proposed method will be beneficial for visualizing lymph vessels.

Purpose: Quantitative diagnosis of the degree of fibrosis progression is currently a focus of attention for fatty liver in nonalcoholic steatohepatitis (NASH). However, previous studies have focused on either lipid droplets or fibrotic tissue, and few have reported the evaluation of both in patients whose livers contain adipose and fibrous features. Our aim was to evaluate fibrosis tissue and lipid droplets in the liver. Methods: We used an analytical method combining the multi-Rayleigh (MRA) model and a healthy liver structure filter (HLSF) as a technique for statistical analysis of the amplitude envelope to estimate fat and fibrotic volumes in clinical datasets with different degrees of fat and fibrosis progression. Results: Fat mass was estimated based on the non-MRA fraction corresponding to the signal characteristics of aggregated lipid droplets. Non-MRA fraction has a positive correlation with fat mass and is effective for detecting moderate and severe fatty livers. Progression of fibrosis was estimated using MRA parameters in combination with the HLSF. The proposed method was used to extract non-healthy areas with characteristics of fibrotic tissue. Fibrosis in early fatty liver suggested the possibility of evaluation. On the other hand, fat was identified as a factor that reduced the accuracy of estimating fibrosis progression in moderate and severe fatty livers. Conclusion: The proposed method was used to simultaneously evaluate fat mass and fibrosis progression in early fatty liver, suggesting the possibility of quantitative evaluation for discriminating between lipid droplets and fibrous tissue in the early fatty liver.

An extraction of fibrotic signals in fibrotic liver will contribute to diagnosis of liver fibrosis. As the fibrotic signals show higher variance of envelope amplitudes compared to that of norma tissue signals, the extraction of higher amplitude signals can extract a part of fibrotic signals. A constant false alarm rate (CFAR) processing is one of the thresholding methods to extract higher amplitude signals with quantitatively setting a threshold to be that the false alarm rate, that is, the false extraction probability of background signals, becomes constant. In a previous study, a Rayleigh based CFAR processing was proposed to extract the fibrotic signals because a probability density function (PDF) of normal liver tissue can be modeled by a Rayleigh distribution. However, in a progressive liver fibrosis, the PDF greatly deviates from the Rayleigh distribution; therefore, the PDF of background signals cannot be modeled by the Rayleigh distribution. In this study, we examined a multi-Rayleigh based CFAR processing. The multi-Rayleigh model is a PDF model for fibrotic liver and can extract the normal tissue component. Therefore, the threshold value was set to be that the false alarm rate of PDF of normal tissue component in the multi-Rayleigh model becomes constant. The in vivo data analysis showed that the multi-Rayleigh based CFAR processing increased the extracted rate of fibrotic signals for the liver fibrosis without increasing that for the non-fibrotic liver. Thus, the multi-Rayleigh based CFAR processing has a potential to improve the sensitivity of extraction of fibrotic signals, that will contribute to the higher-sensitivity detection of liver fibrosis.

Introduction: Assessing the stage of liver fibrosis during the diagnosis and follow-up of patients with diffuse liver disease is crucial. The tissue structure in the fibrotic liver is reflected in the texture and contrast of an ultrasound image, with the pixel brightness indicating the intensity of the echo envelope. Therefore, the progression of liver fibrosis can be evaluated non-invasively by analyzing ultrasound images. Methods: A convolutional-neural-network (CNN) classification of ultrasound images was applied to estimate liver fibrosis. In this study, the colorization of the ultrasound images using echo-envelope statistics that correspond to the features of the images is proposed to improve the accuracy of CNN classification. In the proposed method, the ultrasound image is modulated by the 3rd- and 4th-order moments of pixel brightness. The two modulated images and the original image were then synthesized into a color image of RGB representation. Results and Discussion: The colorized ultrasound images were classified via transfer learning of VGG-16 to evaluate the effect of colorization. Of the 80 ultrasound images with liver fibrosis stages F1–F4, 38 images were accurately classified by the CNN using the original ultrasound images, whereas 47 images were classified by the proposed method.

Abstract Previous studies have shown that shear wave elastography of liver tissue can be unstable due to factors such as uncertainties in the acoustic radiation force (ARF) irradiation due to the influence of tissues near the surface and the complexity of the liver’s structure and its physical properties. This study aims to verify the influence of near-surface tissues on ARF and the effect of tissue structure on shear wave propagation and shear wave velocity (SWV) evaluation using the wave propagation simulations by the elastic finite-difference time domain method. It is found that the ARF becomes weakly focused on multiple locations due to refraction of longitudinal waves by near-surface tissues, and multiple shear waves of small amplitude are propagated. However, a macroscopic SWV assessment, as in clinical practice, reduces the influence of near-surface tissues because the microscopic assessment results are averaged over the near-surface tissues.

Abstract We attempted to visualize a single microbubble driven by acoustic radiation force using a combination of pulse inversion Doppler and plane wave imaging. Commercial microbubbles, Sonazoid^® underwent ultrasound exposure with a center frequency of 5.2 MHz, a pulse repetition frequency of 4 kHz, and a negative peak sound pressure of 1.59 MPa. It succeeded in separately detecting individual microbubbles with high sensitivity. The disappearance of freely-translating microbubbles could be observed as a broadened spectrum of Doppler signal, i.e. a pseudo-Doppler effect. However, the trend was not apparent in the case of wall-colliding microbubbles.

Abstract We compared the evaluation accuracy of amplitude envelope statistics under the transmission and reception conditions of compounded plane wave imaging (CPWI) and focused beam imaging (FBI). In a basic study using a homogeneous phantom, we found that the amplitude gradient in the depth direction and the point spread function in the lateral direction spread in the FBI reduced the accuracy of evaluation in amplitude envelope statistics. On the other hand, CPWI showed a more stable evaluation than FBI because of the elimination of sound field characteristics. In CPWI, the multi-Rayleigh model discriminated signals from two types of scatterer with high accuracy in the evaluation using phantoms mimicking fatty liver. It was confirmed that the combination of CPWI and the multi-Rayleigh model is effective for detecting early fatty liver disease. The results show that CPWI is effective for improving the robustness of amplitude envelope statistics.

Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications. Thermal ablation, which includes radiofrequency ablation and microwave ablation, is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with ≤3 lesions measuring ≤3 cm and preserved liver function. The short- and long-term outcomes of patients are comparable with those achieved with surgical resection. Despite their nonmalignant nature, some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement. Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment. This review describes the recent concepts, progress, and limitations of ablation-based treatment for benign liver tumors.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4-12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from -36 to -49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s-1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

PURPOSE: The aim of this study was to elucidate the frequency dependence of the speed of sound (SoS) and attenuation coefficients in phantoms with controlled attenuation properties (scatterer density, scatterer size, absorption control material) and rat livers. METHODS: The frequency dependence of SoS and attenuation coefficients were evaluated with ultrasound (1-15 MHz) by observing multiple phantoms with different scatterer sizes, densities, and presence or absence of evaporated milk as absorbing media. Normal and fatty model rat livers were examined with the same protocol. RESULTS: The phantom results revealed that the scatterer density and SoS of the base media were the dominant factors causing the changes in SoS. Frequency dependence was not observed in SoS. Assessment of the attenuation coefficient showed that the frequency dependence was mainly affected by absorption attenuation when the scatterer was as small as a hepatocyte (i.e. ≤ 10 µm). Scattering attenuation was also observed to affect frequency dependence when the scatterer was as large as lipid droplets (i.e. ≤ 40 µm). CONCLUSION: Assuming a consistent size of the main scatterers in the evaluation medium, the frequency dependence of the SoS and attenuation coefficients may provide insight into the scatterer density and the contribution of absorption and scattering attenuation. Further studies in the higher frequency band (up to about 50 MHz) are expected to advance the clinical application of high-frequency ultrasound.

Abstract This study investigates how the translational velocity of phospholipid-coated bubbles caused by acoustic radiation force depends on their size. The translations of bubbles with mean radii of 0.9–5 μm were experimentally evaluated at five ultrasound frequency conditions (3.5, 5, 7.5, 10, and 15 MHz). We compared experimental data with theoretical prediction using a viscoelastic interfacial rheological model and a model suitable for high amplitude oscillation. The results suggested that the translation of bubbles could be enhanced for a mean radius of 1–3 μm but echo intensity could not.

This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the International Society of Lymphology (ISL) stage. Ultrasonic measurements were made around the middle thigh (n = 150). Radiofrequency data were acquired using a clinical scanner and 8-MHz linear probe. Envelope statistical analysis was performed using constant false alarm rate processing and homodyned K (HK) distribution. The attenuation coefficient was calculated using the spectral log-difference technique. The backscatter coefficient (BSC) was obtained by the reference phantom method with attenuation compensation according to the attenuation coefficients in the dermis and hypodermis, and then effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated with a Gaussian model. Receiver operating characteristic curves of QUS parameters were obtained using a linear regression model. A single QUS parameter with high area under the curve (AUC) differed between the dermis (ESD and EAC) and hypodermis (HK) parameters. The combinations with ESD and EAC in the dermis, HK parameters in the hypodermis and typical features (dermal thickness and echogenic regions in the hypodermis) improved classification performance between ISL stages 0 and ≥I (AUC = 0.90 with sensitivity of 75% and specificity of 91%) in comparison with ESD and EAC in the dermis (AUC = 0.82) and HK parameters in the hypodermis (AUC = 0.82). In vivo QUS assessment by BSC and envelope statistical analyses can be valuable for non-invasively classifying an extremely early stage of lymphedema, such as ISL stage I, and following its progression.

PURPOSE: To quantify the bias of shear wave speed (SWS) measurements in a viscoelastic phantom across six different ultrasound (US) systems and to compare the SWS with those from transient elastography (TE) and magnetic resonance elastography (MRE). METHODS: A viscoelastic phantom of stiffness representing fibrotic liver or healthy thyroid was measured with nine (linear probe) and 10 (convex probe) modes of six different US-based shear wave elastography (SWE) systems using linear and convex probes. SWS measurements of three regions of interest were repeated thrice at two focal depths, coupling the probe to the phantom using a jig. An MRE system using three motion-encoding gradient frequencies of 60, 90, and 120 Hz and TE were also used to measure the stiffness of the phantom. RESULTS: The SWS from different SWE systems had mean coefficients of variation of 9.0-9.2% and 5.4-5.6% with linear and convex probes, respectively, in viscoelastic phantom measurement. The focal depth was a less significant source of SWS variability than the system. The total average SWS obtained with US-SWE systems was 19.9% higher than that obtained with MRE at 60 Hz, which is commonly used in clinical practice, and 31.5% higher than that obtained with TE using the M probe. CONCLUSIONS: Despite the measurement biases associated with the SWE systems, biases were not necessarily consistent, and they changed with the probes used and depth measured. The SWS of the viscoelastic phantom obtained using different modalities increased according to the shear wave frequency used.

Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension.

BACKGROUND: Increased skin and subcutaneous tissue stiffness in patients with early-stage lymphedema has been reported. The purpose of this study was to examine the use of shear wave elastography (SWE) for evaluating lower extremity lymphedema (LEL). METHODS: For 10 lower extremities of normal controls and 72 limbs of patients with gynecological cancer whose lymphatic function was categorized into six stages based on the range of dermal backflow (DBF) observed in indocyanine green (ICG) lymphography, SWE was performed and shear wave velocity (SWV) of the dermis and three layers of subcutaneous tissue at the thigh and calf were recorded. Twenty-five patients underwent thigh tissue histological and dermal thickness examinations. RESULTS: The strongest correlation between the ICG DBF stage and SWV during SWE was observed on the dermal layer of the thigh (p < 0.01, R = 0.67). There was a significant correlation between the dermal thickness of the thigh and the ICG DBF stage (p < 0.01, R = 0.87) and also between the dermal thickness of the thigh and SWV (p < 0.01, R = 0.73). CONCLUSION: Noninvasive, objective evaluation of LEL severity using SWE was well correlated with lymphatic function as determined by ICG lymphography. The DBF changes in the dermis of the thigh best reflected the changes in lymphatic function. Dermal thickness variations may partially account for differences in SWV.

In the field of clinical ultrasound, the full digitalization of diagnostic equipment in the 2000s enabled the technological development of quantitative ultrasound (QUS), followed by multiple diagnostic technologies that have been put into practical use in recent years. In QUS, tissue characteristics are quantified and parameters are calculated by analyzing the radiofrequency (RF) echo signals returning to the transducer. However, the physical properties (and pathological level structure) of the biological tissues responsible for the imaging features and QUS parameters have not been sufficiently verified as there are various conditions for observing living tissue with ultrasound and inevitable discrepancies between theoretical and actual measurements. A major issue of QUS in clinical application is that the evaluation results depend on the acquisition conditions of the RF echo signal as the source of the image information, and also vary according to the model of the diagnostic device. In this paper, typical examples of QUS techniques for evaluating attenuation, speed of sound, amplitude envelope characteristics, and backscatter coefficient in living tissues are introduced. Exemplary basic research and clinical applications related to these technologies, and initiatives currently being undertaken to establish the QUS method as a true tissue characterization technology, are also discussed.

Lipid-coated microbubbles (MBs) with an indocyanine green (ICG) derivative were fabricated for ultrasound and near-infrared (NIR) fluorescence dual imaging. We characterized the NIR-fluorescence intensity, stability and viscoelastic properties of the encapsulating lipid shell, focusing on the influence of the ICG derivative and lipid compositions. In terms of the NIR fluorescence intensity, the fluorescence intensity of the MBs (with the ICG derivative) was significantly affected by the lipid composition of the MB shell. Regarding the contrast agent used for ultrasound imaging, the stability of the MBs and viscoelastic properties of shell also depended on the lipid compositions, while the incorporation of the ICG derivative into the MB shells had a negligible effect. The performance of this contrast agent for ultrasound and NIR fluorescence dual-imaging exhibited a significant trade-off relationship for the lipid composition.

We investigated the differences between the transmission (Tx)/reception (Rx) sound fields for target and reference signals using a reference phantom method (RPM) to assess the stability of backscattering coefficient (BSC) evaluation. A clinical ultrasound scanner and two types of phased linear array transducer with low and high frequencies were used to evaluate the BSCs for two types of homogenous phantom with different attenuation coefficients and BSCs. Different Tx/Rx sound fields were reproduced using different combinations of Tx focus depths and aperture sizes. Target signals with Tx conditions that were both the same as and different from those for the reference signals were used to produce signals with different Tx/Rx sound fields. The differences in the Tx/Rx sound fields affected the depth dependence of the evaluated BSC. It was concluded that this can be a factor creating variation in the BSC for homogenous targets.

Previous studies have shown that evaluation results of shear wave elastography were unstable due to factors such as liver structure and complexity of physical properties. The present study attempts to verify the influence of liver microstructure (fat droplets and fibrous tissue) on the shear wave and shear wave velocity (SWV) evaluation using a shear wave propagation simulation by the elastic finite-difference time-domain method. It was found that disruption of the shear wave causes variations in the SWV of the liver around fat droplets, and the SWV of the fibrous tissue depends on the shear wave propagation direction and the tissue shape. In a nonalcoholic steatohepatitis liver, which contains fat and fiber, the influences of these two tissues are synergistically reflected in the SWV evaluation.

In previous studies, the double-Nakagami (DN) model has been proposed for fatty liver assessment and applied to in vivo rat livers and clinical data sets. The healthy liver structure filter (HLSF) method, which extracts non-healthy areas using two DN parameters, has also been proposed. In this paper, we first verify the accuracy of the DN model and the HLSF method for acoustic fields at 15 and 5 MHz, which were reproduced using numerical simulation. We then apply the method to clinical data sets of livers observed using a frequency of 3 MHz and investigate the method's clinical usefulness. A positive correlation (r = 0.28) was found between the ratio of the non-healthy area and fat mass. Although the results were inferior to the results produced using 15 MHz ultrasound (r = 0.96), we found that it was possible to detect the difference between a normal liver and a fatty liver even at a lower frequency. (C) 2021 The Japan Society of Applied Physics

Hepatocellular carcinoma (HCC) is a common cancer worldwide. Recent international guidelines request an identification of the stage and patient background/condition for an appropriate decision for the management direction. Radiomics is a technology based on the quantitative extraction of image characteristics from radiological imaging modalities. Artificial intelligence (AI) algorithms are the principal axis of the radiomics procedure and may provide various results from large data sets beyond conventional techniques. This review article focused on the application of the radiomics-related diagnosis of HCC using radiological imaging (computed tomography, magnetic resonance imaging, and ultrasound (B-mode, contrast-enhanced ultrasound, and elastography)), and discussed the current role, limitation and future of ultrasound. Although the evidence has shown the positive effect of AI-based ultrasound in the prediction of tumor characteristics and malignant potential, posttreatment response and prognosis, there are still a number of issues in the practical management of patients with HCC. It is highly expected that the wide range of applications of AI for ultrasound will support the further improvement of the diagnostic ability of HCC and provide a great benefit to the patients.

In order to quantitatively evaluate the properties of biological tissues from the body surface using ultrasound, it is necessary to comprehensively understand the acoustic properties of both microscopic acoustic properties at the cell level and tissues with macroscopic structure. This chapter introduces the results of evaluating the frequency dependence of the speed of sound of multiple organs using ultrasound in an extremely wide frequency band.

Objective: Hepatic steatosis causes nonalcoholic fatty liver disease and may progress to fibrosis. Ultrasound is the first-line approach to examining hepatic steatosis. Fatty droplets in the liver parenchyma alter ultrasound radiofrequency (RF) signal statistical properties. This study proposes using sample entropy, a measure of irregularity in time-series data determined by the dimension [Formula: see text] and tolerance [Formula: see text], for ultrasound parametric imaging of hepatic steatosis and fibrosis. Methods: Liver donors and patients were enrolled, and their hepatic fat fraction (HFF) ([Formula: see text]), steatosis grade ([Formula: see text]), and fibrosis score ([Formula: see text]) were measured to verify the results of sample entropy imaging using sliding-window processing of ultrasound RF data. Results: The sample entropy calculated using [Formula: see text] 4 and [Formula: see text] was highly correlated with the HFF when a small window with a side length of one pulse was used. The areas under the receiver operating characteristic curve for detecting hepatic steatosis that was [Formula: see text]mild, [Formula: see text]moderate, and [Formula: see text]severe were 0.86, 0.90, and 0.88, respectively, and the area was 0.87 for detecting liver fibrosis in individuals with significant steatosis. Discussion/Conclusions: Ultrasound sample entropy imaging enables the identification of time-series patterns in RF signals received from the liver. The algorithmic scheme proposed in this study is compatible with general ultrasound pulse-echo systems, allowing clinical fibrosis risk evaluations of individuals with developing hepatic steatosis.

A better understanding of ultrasound scattering in a three-dimensional (3D) medium can provide more accurate methods for ultrasound tissue characterization. The possibility of using two-dimensional impedance maps (2DZMs) based on correlation coefficients has shown promise in the case of isotropic and sparse medium [Luchies and Oelze, J. Acoust. Soc. Am. 139, 1557-1564 (2016)]. The present study investigates the use of 2DZMs in order to quantify 3D scatterer properties of dense media from two-dimensional (2D) histological slices. Two 2DZM approaches were studied: one based on the correlation coefficient and the other based on the 2D Fourier transform of 2DZMs. Both 2DZM approaches consist in estimating the backscatter coefficient (BSC) from several 2DZMs, and then the resulting BSC was fit to the theoretical polydisperse structure factor model to yield 3D scatterer properties. Simulation studies were performed to evaluate the ability of both 2DZM approaches to quantify scattering of a 3D medium containing randomly distributed polydisperse spheres or monodisperse ellipsoids. Experimental studies were also performed using the histology photomicrographs obtained from HT29 cell pellet phantoms. Results demonstrate that the 2DZM Fourier transform-based approach was more suitable than the correlation coefficient-based approach for estimating scatterer properties when using a small number of 2DZMs.

Ultrasound imaging is a first-line assessment tool for hepatic steatosis. Properties of tissue microstructures correlate with the statistical distribution of ultrasound backscattered signals, which can be described by the Nakagami distribution (a widely adopted approximation of backscattered statistics). The double Nakagami distribution (DND) model, which combines two Nakagami distributions, was recently proposed for using high-frequency ultrasound to analyze backscattered statistics corresponding to lipid droplets in the fat-infiltrated liver. This study evaluated the clinical feasibility of the DND model in ultrasound parametric imaging of hepatic steatosis by conducting clinical experiments using low-frequency ultrasound dedicated to general abdominal examinations. A total of 204 patients were recruited, and ultrasound image raw data were acquired using a 3.5 MHz array transducer for DND parametric imaging using the sliding window technique. The DND parameters were compared with hepatic steatosis grades identified histologically. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. The results indicated that DND parametric imaging constructed using a sliding window with the side length of five times the pulse length of the transducer provided stable and reliable DND parameter estimations and visualized changes in the backscattered statistics caused by hepatic steatosis. The DND parameter increased with the hepatic steatosis grade. The areas under the ROC curve for identifying hepatic steatosis were 0.76 (>= mild), 0.81 (>= moderate), and 0.82 (>= severe). When using low-frequency ultrasound, DND imaging allows the clinical detection of hepatic steatosis and reflects information associated with lipid droplets in the fat-infiltrated liver.

We studied the effect of acoustic and histopathological features on the ultrasound backscatter properties of lymphedema (LE) dermis. Experimental effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were calculated from a backscatter coefficient using the reflector method for backscattered signals. Predicted parameters were also analyzed using two-dimensional Fourier transforms of the acoustic impedance and histopathological distributions. Backscattered signals were obtained from ex vivo human tissues negative (n = 5) and positive (n = 5) for LE using a laboratory-made scanner with a 14 MHz transducer. Acoustic impedance was analyzed using scanning acoustic microscopy with a 68 MHz transducer, and histopathological features, such as fiber number density and thickness, were assessed with digital histopathology. Both experimental and predicted EACs showed differences (in the range 25.7%-102%) between negative and positive LE. Although the mean and standard deviation of the acoustic impedance were related to the difference in EACs, the ESD and histopathological features were the same regardless of the presence of LE. (C) 2020 The Japan Society of Applied Physics

Clinical ultrasound is widely used for quantitative diagnosis. To clarify the relationship between anatomical and acoustic properties, high resolution imaging using high-frequency ultrasound (HFU) is required. However, when tissue properties are evaluated using HFU, the depth of field (DOF) is limited. To overcome this problem, an annular array transducer, which has a simple structure and produces high-quality images, is applied to HFU measurement. In previous phantom experiments, we demonstrated that the HFU annular array extends the DOF compared to that of a single-element transducer for quantitative ultrasound (QUS) analysis. Here, we extend that work by applying QUS methods to an ex vivo rat liver. The present study demonstrates that an annular array extends the region and improves the resolution for tissue characterization for an excised healthy rat liver. Amplitude envelope statistics and spectral-based analysis are used as QUS methods. (C) 2020 The Japan Society of Applied Physics

The dependence of the speed of sound (SoS) in sliced rat organs on the spatial resolution was investigated through ultrasound analysis at high frequencies (80 and 250 MHz). The radio-frequency echo signals from target were acquired by a scanning acoustic microscopy system developed by the authors that can observe a sample with a transducer. The SoS was evaluated by correcting for the time of flight difference obtained from the wide area measurement. The dependency of the SoS on the spatial resolution was evaluated by applying different filtering methods. Stable analysis was possible after time correction, and fine textures reflecting the microstructure could be observed. The application of different filters to the results obtained at 250 MHz resulted in average SoS values that were similar to those obtained at 80 MHz. These results suggest that the primary targets evaluated 80 and 250 MHz are connective tissue and single cells, respectively. (C) 2020 The Japan Society of Applied Physics

Contrast-enhanced ultrasound imaging using acoustic radiation force, called contrast-enhanced active Doppler ultrasound (CEADUS) imaging, has been proposed for visualizing lymph channels filled with stationary fluid. Based on optical observations and acoustical evaluation, the behaviour of bubbles in a simulated channel during ultrasound exposure was investigated under four conditions for negative peak sound pressure (P-np), at centre frequency of ultrasound and pulse repetition frequency of 15 MHz and 1 kHz, respectively. There was good correlation between the time changes of mean translational velocity for optical evaluation (V-OPT) and acoustical evaluation (V-US). In addition, the maxima of V-OPT and V-US were correlated (R = 0.665) and showed a similar trend proportional to the square of Pnp. These results strongly suggest that the acoustically-evaluated bubble translation has information equal to optically-evaluated one, meaning that the simultaneous observation system is useful to understand the bubble behaviours under CEADUS imaging. (C) 2020 The Japan Society of Applied Physics

Quantitative ultrasound (QUS) methods have been widely used for soft tissue characterization. Spatial resolution (i.e. ultrasound frequency) is an important factor for QUS methods. In a previous study, a double Nakagami (DN) distribution model to echo signals from fatty livers using a 15 MHz transducer was used to permit fine-resolution QUS. This study used a filtering approach to quantify steatosis progression using three QUS parameters obtained by fitting a DN distribution model to experimental envelope data. The filter was designed using QUS parameters obtained from three healthy liver. A strong correlation (r = 0.96, p < 0.001) was found between histologically quantified steatosis percentage and the percentage of the liver having non-healthy liver features. This approach was able to successfully diagnose fatty livers (>20% steatosis percentage) in a dataset of 12 livers ranging from 0% to 90% steatosis. (C) 2020 The Japan Society of Applied Physics

BACKGROUND: To examine in vitro acoustic property of nonalcoholic fatty disease in mouse and human liver to identify nonalcoholic steatohepatitis (NASH). METHODS: The acoustic impedance (× 106 kg/m2/s) was measured in 35 free fatty acids (FFAs, 500 mmol/L) and histologically-diagnosed liver samples of twelve mice (four control, four simple steatosis [SS], and four NASH) and eight humans (two control, three SS, and three NASH), using 80-MHz acoustic microscopy. The sum of percentage (SP) composition of FFAs (SP-FFAs) was also assessed. RESULTS: Median impedance of all FFAs was 0.7 (5 FFAs with impedance 0.7); 17 FFAs with impedance < 0.7 were classified as low-impedance group; and, 13 FFAs with impedance > 0.7 were classified as high-impedance group. The median impedance of the mouse liver decreased from control (1.715), to SS (1.68), to NASH (1.635) (control versus NASH, p = 0.039 without significant differences for the other comparisons, p ≥ 0.1). Similarly, the median impedance of human liver showed decreased from control (1.825), to SS (1.788), to NASH (1.76) (control versus SS, p = 0.023; control versus NASH, p = 0.003; SS versus NASH, p = 0.050). The ratio of SP-FFAs between the low-impedance and high-impedance groups showed an increase in both mice and humans, with significant differences in mice (control versus SS, p < 0.001; control versus NASH, p < 0.001; SS versus NASH, p = 0.003), without significant differences in humans (p ≥ 0.671). CONCLUSION: Lower acoustic impedance based on the intrahepatic composition of FFAs may be characteristic of NASH.

Purpose The backscatter coefficient (BSC) indicates the absolute scatterer property of a material, independently of clinicians and system settings. Our study verified that the BSC differed among the scanners, transducers, and beamforming methods used for quantitative ultrasound analyses of biological tissues. Methods Measurements were performed on four tissue-mimicking homogeneous phantoms containing spherical scatterers with mean diameters of 20 and 30 mu m prepared at concentrations of 0.5 and 2.0 wt%, respectively. The BSCs in the different systems were compared using ultrasound scanners with two single-element transducers and five linear high- or low-frequency probes. The beamforming methods were line-by-line formation using focused imaging (FI) and parallel beam formation using plane wave imaging (PWI). The BSC of each system was calculated by the reference phantom method. The mean deviation from the theoretical BSC computed by the Faran model was analyzed as the benchmark validation of the calculated BSC. Results The BSCs calculated in systems with different properties and beamforming methods well concurred with the theoretical BSC. The mean deviation was below +/- 2.8 dB on average, and within the approximate standard deviation (+/- 2.2 dB at most) in all cases. These variations agreed with a previous study in which the largest error among four different scanners with FI beamforming was 3.5 dB. Conclusion The BSC in PWI was equivalent to those in the other systems and to those of FI beamforming. This result indicates the possibility of ultra-high frame-rate BSC analysis using PWI.