The main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in harmonic energy in the backscattered ultrasound signal, such as energy at the subharmonic, ultraharmonic and higher harmonic frequencies. This harmonic energy is exploited for contrast enhanced imaging to discriminate the contrast agent from surrounding tissue. The amount of harmonic energy that the contrast agent bubbles generate depends on the bubble characteristics in combination with the ultrasound field applied. This paper summarizes different strategies to characterize the UCAs. These strategies can be divided into acoustic and optical methods, which focus on the linear or nonlinear responses of the contrast agent bubbles. In addition, the characteristics of individual bubbles can be determined or the bubbles can be examined when they are part of a population. Recently, especially optical methods have proven their value to study individual bubbles. This paper concludes by showing some examples of optically observed typical behavior of contrast bubbles in ultrasound fields.

Acoustic waves, Backscattered Ultrasound, Bubble characteristics, Contrast agent, Contrast-enhanced imaging, Harmonic analysis, Harmonic energy, Higher harmonics, Light transmission, Medical imaging, Microbubbles, Non-linear response, Optical methods, Resonant systems, Subharmonics, Ultrasonic characterization, Ultrasonic imaging, Ultrasonic transmission, Ultrasonics, Ultrasound contrast, acoustics, article, controlled study, definity, echo contrast medium, echography, hydrodynamics, mathematical analysis, microbubble, optics, optison, perflexane, perflubutane, perflutren, radiation energy, radiation field, radiation scattering, signal processing, sonazoid, sonovue, sulfur hexafluoride,
Medical & Biological Engineering & Computing
Erasmus MC: University Medical Center Rotterdam

de Jong, N, Emmer, M, van Wamel, A, & Versluis, M. (2009). Ultrasonic characterization of ultrasound contrast agents. Medical & Biological Engineering & Computing, 47(8), 861–873. doi:10.1007/s11517-009-0497-1