Relationship between transmission/reception conditions of high-frequency plane wave compounding and evaluation accuracy of extended amplitude envelope statistics.

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.

Detection of Individual Microbubbles by Burst-Wave-Aided Contrast-Enhanced Active Doppler Ultrasonography.

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.

Modified multi-Rayleigh model-based statistical analysis of ultrasound envelope for quantification of liver steatosis and fibrosis.

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.

Release of liposomally formulated near-infrared fluorescent probes included in giant cluster vesicles by ultrasound irradiation.

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.

Assessment of the frequency dependence of acoustic properties on material, composition, and scatterer size of the medium.

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.

Analysis of fluctuation for pixel-pair distance in co-occurrence matrix applied to ultrasonic images for diagnosis of liver fibrosis.

PURPOSE: Chronic liver disease requires careful follow-up during long-term treatment, and development of a quantitative diagnosis method for liver fibrosis based on an ultrasonic imaging system is highly desired. METHODS: Texture analysis using a co-occurrence matrix was applied to both clinical and simulated ultrasonic images of fibrotic livers. A sequence of matrices was generated for pixel-pair distance, r, and texture feature contrast was chosen to examine the response to r in combination with statistical analysis of echo amplitude distribution using a multi-Rayleigh model. RESULTS: The contrast converged with a larger value and fluctuated more significantly in response to r as fibrosis progressed in both the clinical and simulated ultrasonic images. The convergent value rapidly increased at the early stage of fibrosis, and the fluctuation became larger at the advanced stage of fibrosis. Analysis using simulated ultrasonic images with a known fibrous tissue structure theoretically clarified the relationship between contrast behavior and fibrosis progression. CONCLUSION: It was revealed that contrast convergent value and contrast fluctuation provided information on the fibrous tissue structure, and they are expected to be used for quantitative diagnosis of the degree of liver fibrosis.

Ultrasonic distance and velocity measurement using a pair of LPM signals for cross-correlation method: improvement of Doppler-shift compensation and examination of Doppler velocity estimation.

Real-time distance measurement of a moving object with high accuracy and high resolution using an ultrasonic wave is difficult due to the influence of the Doppler effect or the limit of the calculation cost of signal processing. An over-sampling signal processing method using a pair of LPM signals has been proposed for ultrasonic distance and velocity measurement of moving objects with high accuracy and high resolution. The proposed method consists of cross correlation by single-bit signal processing, high-resolution Doppler velocity estimation with wide measurement range and low-calculation-cost Doppler-shift compensation. The over-sampling cross-correlation function is obtained from cross correlation by single-bit signal processing with low calculation cost. The Doppler velocity and distance of the object are determined from the peak interval and peak form in the cross-correlation function by the proposed method of Doppler velocity estimation and Doppler-shift compensation. In this paper, the proposed method of Doppler-shift compensation is improved. Accuracy of the determined distance was improved from approximately within ±140µm in the previous method to approximately within ±10µm in computer simulations. Then, the proposed method of Doppler velocity estimation is evaluated. In computer simulations, accuracy of the determined Doppler velocity and distance were demonstrated within ±8.471mm/s and ±13.87µm. In experiments, Doppler velocities of the motorized stage could be determined within ±27.9mm/s.