Principle of contrast-enhanced ultrasonography

Sonazoid, an ultrasound contrast agent, has been covered by insurance in Japan since January 2007 for the diagnosis of hepatic mass lesions and is widely used for diagnosing not only primary liver cancer but also liver metastases such as those from breast cancer and colorectal cancer. Contrast-enhanced ultrasound for breast mass lesions has been covered by insurance since August 2012 after phase II and phase III clinical trials showed that the diagnostic performance was significantly superior to that of B-mode and contrast-enhanced magnetic resonance imaging. This paper describes the principles of imaging techniques in contrast-enhanced ultrasonography including the filter, pulse inversion, amplitude modulation, and amplitude-modulated pulse inversion methods. The pulse inversion method, which visualizes the second-harmonic component using the nonlinear scattering characteristics of the contrast agent, is widely used regardless of the contrast agent and target organ because of its high resolution. Sonazoid has a stiffer shell and requires a higher acoustic amplitude than Sonovue to generate nonlinear vibrations. The higher transmitted sound pressure generates more tissue harmonic components. Since pulse inversion allows visualization of the tissue harmonic components, amplitude modulation and amplitude-modulated pulse inversion, which include few tissue harmonic components, are primarily used. Amplitude modulation methods detect nonlinear signals from the contrast agent in the fundamental band. The mechanism of the amplitude modulation is considered to be changes in the echo signal's phase depending on the sound pressure. Since the tissue-derived component is minor in amplitude modulation methods, good contrast sensitivity can be obtained.