吉田 憲司

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 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.

The article “Modified multi-Rayleigh model-based statistical analysis of ultrasound envelope for quantification of liver steatosis and fibrosis”, written by Yuki Ujihara, Kazuki Tamura, Shohei Mori, Dar-In Tai, Po-Hsiang Tsui, Shinnosuke Hirata, Kenji Yoshida, Hitoshi Maruyama and Tadashi Yamaguchi, was originally published Online First without Open Access. After publication in volume 51, issue 1, pages 5–16 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2023 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0. The original article has been corrected.

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.

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.

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.

Detection of tumors and regional lymph nodes during surgery has been proposed in the diagnosis of lymphatic metastasis and the surgical treatment of malignant diseases. Giant cluster vesicles (GCVs), including liposomally formulated indocyanine green (LP-ICG) derivatives, are a possible candidate for agents to realize the two contradictory properties, i.e., retention in tissue for lesion-marking and trace for sentinel lymph nodes (SLNs) identification. We attempted to release the LP-ICG derivatives from GCVs using ultrasound contrast agents (UCAs) under ultrasound irradiation. An absorption spectrophotometer quantitatively evaluated the amounts of released LP-ICG derivatives. As a result, we demonstrated that it depended on conditions for sound pressure, burst length, and number density of UCAs, and had a sound pressure threshold independent of burst length and number density of UCAs. The results will aid to determine appropriate conditions to maximize the released amount of LP-ICG derivatives while keeping safety.

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.

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 In a previous study, an annular-array transducer was employed to characterize homogeneous scattering phantoms and excised rat livers using backscatter envelope statistics and frequency domain analysis. A sound field correction method was also applied to take into account the average attenuation of the entire scattering medium. Here, we further generalized the evaluation of backscatter coefficient (BSC) using the annular array in order to study skin tissues with a complicated structure. In layered phantoms composed of two types of media with different scattering characteristics, the BSC was evaluated by the usual attenuation correction method, which revealed an expected large difference from the predicted BSC. In order to improve the BSC estimate, a correction method that applied the attenuation of each layer as a reference combined with a method that corrects based on the attenuation of the analysis position were applied. It was found that the method using the average attenuation of each layer is the most effective. This correction method is well adapted to the extended depth of field provided by an annular array.

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.

Abstract In contrast enhancement ultrasound (CEUS), the vasculature image can be formed from nonlinear echoes arising from microbubbles in a blood flow. The use of binary-coded pulse compression is promising for improving the contrast of CEUS images by suppressing background noise. However, the amplitudes of nonlinear echoes can be reduced, and sidelobes by nonlinear echoes can occur depending on the binary code. Optimal Golay codes with slight nonlinear-echo reduction and nonlinear sidelobe have been proposed. In this study, CEUS images obtained by optimal Golay pulse compression are evaluated through experiments using Sonazoid microbubbles flowing in a tissue-mimicking phantom.

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.

Abstract A blood mimicking fluid (BMF) is imperative for the evaluation of Doppler ultrasound. Doppler ultrasound still causes errors due to some artifacts such as aliasing and presence of grating lobes. One of the other velocimeters is the optical particle image velocimeter (PIV). This study initially developed an in vitro measurement system for analyzing flowing BMF with ultrasonic and optical PIVs. The acoustic properties such as speed of sound, attenuation, and backscatter coefficient of BMF equivalent to the human blood, used for both ultrasonic and optical PIVs were analyzed in a frequency range of 4-12 MHz. The velocity profiles were estimated by ultrasonic and optical PIVs using a block matching method. A difference between velocities obtained by ultrasonic and optical data was within 4.0% using BMF with 20 µm polyamide particle at 0.2% concentration that realized the acoustic properties and speckle patterns similar to those in ultrafast ultrasound blood flow imaging.

高速超音波イメージングは血管や循環器系における血流速ベクトル評価に応用されている.流速推定値は,エイリアシングやグレーティングローブなどの超音波固有のアーチファクトによって推定誤差が表れる場合がある.粒子分布を可視化し速度計測を行える他のシステムの一つとして,光学的粒子画像追跡法(particle image velocimetry:PIV)が挙げられる.本報告では超音波・光学システムを併用した流れ場観察システムを構築し,複数種の血液模擬溶液の流速を評価した.また,超音波・光学システムでの安定した速度推定が可能な粒子径や濃度条件を整理するとともに,基礎的な音響特性(音速・減衰係数・後方散乱係数)を評価し,IEC規格が示す血液模擬溶液の推奨値と比較した.超音波および光学システムにおいて推定した流速は,直径20μmのポリアミド粒子が溶液中に0.2%存在している場合,同等(誤差4.0%)であるとともにIEC規格が示す音響特性の推奨値の範囲内かつ超音波像においてスペックルパタンが保持されていることを確認した.(著者抄録)

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

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.

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.

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.

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

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

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

Purpose Radio-frequency (RF) signals from the most dominant scatterer in a dermis, i.e., collagen fibers, are collected as backscattered signals. We aim to confirm the frequency dependence of the spatial distribution of features in ultrasound images, as well as the attenuation coefficient (AC) and backscatter coefficient (BSC) of skin tissue without [LE (-)] and with lymphedema [LE (+)]. Methods Measurement samples (n = 13) were excised from human skin tissue with LE (-) and middle severity LE (+). A laboratory-made scanner and single-element concave transducers (range 9-47 MHz) were used to measure RF data. A localized AC was computed from the normalized power spectrum using the linear least squares technique. The reflector method and compensation technique of the attenuation of tissue were applied to calculate the BSC. In addition, effective scatterer diameter (ESD), effective acoustic concentration (EAC), and integrated BSC (IBS) were calculated from the BSC as the benchmark to differentiate LE (-) and LE (+) tissues. Results High-frequency ultrasound displayed different echogenicity and texture compared between LE (-) and LE (+) in all transducers. The AC for LE (-) (0.22 dB/mm/MHz) and LE (+) (0.29 dB/mm/MHz) was comparable. BSC in LE (-) and LE (+) increased linearly with each transducer. The difference of intercept of the BSC between LE (-) and LE (+) indicated that both EAC and IBS of LE (+) were higher than that of LE (-). In contrast, ESD correlated with the slope of the BSC demonstrated the same tendency for both LE (-) and LE (+). These tendencies appeared for each transducer independent of the frequency bandwidth. Conclusion Frequency independence of AC and BSC in LE (-) and LE (+) was confirmed. Several 9- to 19-MHz ultrasound beams are sufficient for BSC analysis to discriminate LE (-) and LE (+) in terms of the penetration depth of the ultrasound.

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.

In this report, a method is proposed to quantify the translation of ultrasound contrast agent (UCA) microbubbles driven by acoustic radiation for the detection of channels filled with stationary fluid. The authors subjected UCA microbubbles in a channel with diameters of 0.1 and 0.5 mm to ultrasound pulses with a center frequency of 14.4 MHz. The translational velocity of the UCA microbubbles increased with the sound pressure and pulse repetition frequency (PRF) of the transmitted ultrasound. The mean translational velocity reached 0.75 mm/s at a negative peak sound pressure of 2.76 MPa and a PRF of 2 kHz. This trend agreed with the theoretical prediction, which indicated that the translational velocity was proportional to the square of the sound pressure and the PRF. Furthermore, an experiment was carried out with a phantom that mimics tissue and found that the proposed method aided in detection of the channel, even in the case of a low contrast-echo to tissue-echo ratio. The authors expect to develop the proposed method into a technique for detecting lymph vessels.

Microbubbles shelled with soft materials are expected to find applications as ultrasound-sensitive drug delivery systems, including through sonoporation. Microbubbles with specific vibrational characteristics and long intravascular persistence are required for clinical uses. To achieve this aim, the kinetics of the microbubble shell components at the gas/liquid interface while being subjected to ultrasound need to be better understood. This paper investigates the vibration characteristics and lifetime of single microbubbles coated with a poloxamer surfactant, Pluronic F-68, and 1,2-dimyristoyl-snglycero-3-phosphocholine (DMPC) under ultrasound irradiation. Air-and perfluorohexane (PFH)-filled microbubbles coated with Pluronic F-68 and DMPC at several concentrations (0 to 10(-2) mol L-1) were produced. An optical measurement system using a laser Doppler vibrometer and microscope was used to observe the radial vibration mode of single microbubbles. The vibrational displacement amplitude and resonance radius of Pluronic- or DMPC-coated microbubbles were found to depend very little on the concentrations. The resonance radius was around 65 mu m at 38.8 kHz under all the experimental conditions investigated. The lifetime of the microbubbles was investigated simultaneously by measuring their temporal change in volume, and it was increased with Pluronic concentration. Remarkably, the oscillation amplitude of the bubble has an effect on the bubble lifetime. In other words, larger oscillation under the resonance condition accelerates the diffusion of the inner gas.

High-frequency ultrasound (HFU, >20 MHz) and quantitative ultrasound (QUS) methods permit a means to understand the relationship between anatomical and acoustic characteristics. In our previous research, we showed that analyzing the acoustic scattering with HFU was an effective method for noninvasive diagnosis. However, the depth of field (DOF) of HFU transducers was limited, which constrains the range of QUS analysis. In this study, we seek to improve the accuracy of HFU, QUS-based parameters on the envelope statistics and frequency-based analysis by using an annular array that allows for an extended DOF. A 20-MHz annular-array transducer with five elements was employed to obtain signals which were beamformed in post-processing. Two kinds of low concentration scattering phantoms were scanned with 30-μm step size. Two QUS analysis techniques were employed: the Nakagami distribution and the reflector method. The results demonstrated that the annular array provides a stable analysis over an extended axial range.

We aim to develop an ultrasonic tissue characterization method for the follow-up of healing ulcers by diagnosing collagen fibers properties. In this paper, we demonstrated a computer simulation with simulation phantoms reflecting irregularly distributed collagen fibers to evaluate the relationship between physical properties, such as number density and periodicity, and the estimated characteristics of the echo amplitude envelope using the homodyned-K distribution. Moreover, the consistency between echo signal characteristics and the structures of ex vivo human tissues was verified from the measured data of normal skin and nonhealed ulcers. In the simulation study, speckle or coherent signal characteristics are identified as periodically or uniformly distributed collagen fibers with high number density and high periodicity. This result shows the effectiveness of the analysis using the homodyned-K distribution for tissues with complicated structures. Normal skin analysis results are characterized as including speckle or low-coherence signal components, and a nonhealed ulcer is different from normal skin with respect to the physical properties of collagen fibers. (C) 2018 The Japan Society of Applied Physics