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.

In this study, the speed of sound (SOS) of two types of rat livers (eight normal livers, four cirrhotic livers) was measured with a scanning acoustic microscope using two transducers, one of which had an 80-MHz and the other a 250-MHz center frequency. The 250-MHz transducer had a better spatial resolution adapted to studying fiber or hepatic parenchymal cells. In normal livers, averages of the SOS values were from 1598 to 1677 m/s at 80-MHz and from 1568 to 1668 m/s at 250-MHz. In the fiber tissue of cirrhotic livers, averages of the SOS values were from 1645 to 1658 m/s at 80-MHz and from 1610 to 1695 m/s at 250-MHz, while the SOS values in the other tissue of cirrhotic livers ranged from 1644 to 1709 m/s at 80-MHz and from 1641 to 1715 m/s at 250-MHz. In one liver, SOS in fiber tissue was larger than that of tissues without fiber while in others it was lower. The resulting two-dimensional SOS maps provide a unique quantitative insight of liver acoustic microstructures in a healthy liver and in a cirrhotic ones. This study would be helpful to understand the complex relationship between acoustic properties and liver disease including fiber tissue.

To characterize skin ulcers for bacterial infection, quantitative ultrasound (QUS) parameters were estimated by the multiple statistical analysis of the echo amplitude envelope based on both Weibull and generalized gamma distributions and the ratio of mean to standard deviation of the echo amplitude envelope. Measurement objects were three rat models (noninfection, critical colonization, and infection models). Ultrasound data were acquired using a modified ultrasonic diagnosis system with a center frequency of 11 MHz. In parallel, histopathological images and two-dimensional map of speed of sound (SoS) were observed. It was possible to detect typical tissue characteristics such as infection by focusing on the relationship of QUS parameters and to indicate the characteristic differences that were consistent with the scatterer structure. Additionally, the histopathological characteristics and SoS of noninfected and infected tissues were matched to the characteristics of QUS parameters in each rat model.

Many methods for the analysis of amplitude envelope statistics have been proposed in recent decades to enable echo signal characterization and realize quantitative diagnosis based on these statistics. In the statistical analysis of ultrasound signals, the spatial resolution of the signal is an important factor. An analysis method that offers higher sensitivity than the current analysis model is required to allow the effective use of recently developed high-resolution ultrasonic diagnostic equipment. In this study, we propose a multi-amplitude envelope statistical model called the double Nakagami probability density function (PDF) model that assumes the physical structure of fatty liver disease under high-frequency ultrasound excitation. Application of the proposed model to actual rat livers demonstrated that it was possible to evaluate fatty liver disease at an early stage with a lower scatterer density than that of a normal liver. However, it is difficult to detect the disease at this stage using existing technology.