A review on B/A measurement methods with a clinical perspective.

The nonlinear parameter of ultrasound B/A has shown to be a useful diagnostic parameter, reflecting medium content, structure, and temperature. Despite its recognized values, B/A is not yet used as a diagnostic tool in the clinic due to the limitations of current measurement and imaging techniques. This review presents an extensive and comprehensive overview of the techniques developed for B/A measurement of liquid and liquid-like media (e.g., tissue), identifying the methods that are most promising from a clinical perspective. This work summarizes the progress made in the field and the typical challenges on the way to B/A estimation. Limitations and problems with the current techniques are identified, suggesting directions that may lead to further improvement. Since the basic theory of the physics behind the measurement strategies is presented, it is also suited for a reader who is new to nonlinear ultrasound.

Acoustic characterization of tissue-mimicking materials for ultrasound perfusion imaging research.

Materials with well-characterized acoustic properties are of great interest for the development of tissue-mimicking phantoms with designed (micro)vasculature networks. These represent a useful means for controlled in-vitro experiments to validate perfusion imaging methods such as Doppler and contrast-enhanced ultrasound (CEUS) imaging. In this work, acoustic properties of seven tissue-mimicking phantom materials at different concentrations of their compounds and five phantom case materials are characterized and compared at room temperature. The goal of this research is to determine the most suitable phantom and case material for ultrasound perfusion imaging experiments. The measurements show a wide range in speed of sound varying from 1057 to 1616 m/s, acoustic impedance varying from 1.09 to 1.71 × 106 kg/m2s, and attenuation coefficients varying from 0.1 to 22.18 dB/cm at frequencies varying from 1 MHz to 6 MHz for different phantom materials. The nonlinearity parameter B/A varies from 6.1 to 12.3 for most phantom materials. This work also reports the speed of sound, acoustic impedance and attenuation coefficient for case materials. According to our results, polyacrylamide (PAA) and polymethylpentene (TPX) are the optimal materials for phantoms and their cases, respectively. To demonstrate the performance of the optimal materials, we performed power Doppler ultrasound imaging of a perfusable phantom, and CEUS imaging of that phantom and a perfusion system. The obtained results can assist researchers in the selection of the most suited materials for in-vitro studies with ultrasound imaging.

B/A Measurement of Clear Cell Renal Cell Carcinoma versus Healthy Kidney Tissue.

The acoustic parameter of non-linearity B/A has been found capable of discriminating some types of pathological tissue from healthy tissue. The literature on the utility of B/A for cancer diagnostics is very limited, with measurements on the human breast and liver. This work expands the current research on cancer diagnostics by B/A assessment of eight slices of human clear cell renal cell carcinoma (ccRCC) from two patients and four slices of healthy kidney tissue from two healthy kidney samples. The Wilcoxon test identified the B/A distribution of malignant tissue as not significantly different from that of healthy tissue. An alternative way of defining outliers resulted in median B/A values of 8.1 for ccRCC and 6.8 for healthy tissue (p < 0.05). Acoustic attenuation at 2.1 MHz was significantly greater (p < 0.05) for ccRCC (1.7 dB/cm) than for healthy tissue (1.0 dB/cm). The observed differences in the measured values suggest that B/A and acoustic attenuation may represent potential diagnostic markers of ccRCC. More data and an improved experimental design are required to provide a definitive conclusion on the utility of B/A for cancer diagnostics.

Experimental acoustic characterization of an endoskeletal antibubble contrast agent: First results.

PURPOSE: An antibubble is an encapsulated gas bubble with an incompressible inclusion inside the gas phase. Current-generation ultrasound contrast agents are bubble-based: they contain encapsulated gas bubbles with no inclusions. The objective of this work is to determine the linear and nonlinear responses of an antibubble contrast agent in comparison to two bubble-based ultrasound contrast agents, that is, reference bubbles and SonoVue TM . METHODS: Side scatter and attenuation of the three contrast agents were measured, using single-element ultrasound transducers, operating at 1.0, 2.25, and 3.5 MHz. The scatter measurements were performed at acoustic pressures of 200 and 300 kPa for 1.0 MHz, 300 kPa, and 450 kPa for 2.25 MHz, and 370 and 560 kPa for 3.5 MHz. Attenuation measurements were conducted at pressures of 13, 55, and 50 kPa for 1.0, 2.25, and 3.5 MHz, respectively. In addition, a dynamic contrast-enhanced ultrasound measurement was performed, imaging the contrast agent flow through a vascular phantom with a commercial diagnostic linear array probe. RESULTS: Antibubbles generated equivalent or stronger harmonic signal, compared to bubble-based ultrasound contrast agents. The second harmonic side-scatter amplitude of the antibubble agent was up to 3 dB greater than that of reference bubble agent and up to 4 dB greater than that of SonoVue TM at the estimated concentration of 8 × 10 4 bubbles/mL. For ultrasound with a center transmit frequency of 1.0 MHz, the attenuation coefficient of the antibubble agent was 8.7 dB/cm, whereas the attenuation coefficient of the reference agent was 7.7 and 0.3 dB/cm for SonoVue TM . At 2.25 MHz, the attenuation coefficients were 9.7, 3.0, and 0.6 dB/cm, respectively. For 3.5 MHz, they were 4.4, 1.8, and 1.0 dB/cm, respectively. A dynamic contrast-enhanced ultrasound recording showed the nonlinear signal of the antibubble agent to be 31% greater than for reference bubbles and 23% lower than SonoVue TM at a high concentration of 2 × 10 6 bubbles/mL. CONCLUSION: Endoskeletal antibubbles generate comparable or greater higher harmonics than reference bubbles and SonoVue TM . As a result, antibubbles with liquid therapeutic agents inside the gas phase have high potential to become a traceable therapeutic agent.

On the Relationship between Dynamic Contrast-Enhanced Ultrasound Parameters and the Underlying Vascular Architecture Extracted from Acoustic Angiography.

Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA.