吉田 憲司

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.

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 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.

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.

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

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.

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