Modeling of high-frequency ultrasound contrast agents.

Abstract

High-frequency applications of ultrasound contrast agents continue to develop with their increasing use for imaging intravascular locations as well as dermal and ocular tissue. However, conventional ultrasound contrast agents were originally designed for traditionally lower diagnostic frequencies. The optimal contrast agent design and related acoustic forcing methods for high-frequency applications are important topics of on-going research. In this respect,ultrasound contrast agent models are reviewed and, in particular, the role of the shell is highlighted for novel high-frequency applications. Shell material and related stability issues are discussed in terms of the constitutive equation assumptions. The concept of auto-resonance, which may be achieved by a slowly varying forcing frequency, is introduced as a method for enhancing the subharmonic response of free or bound agents. The phase locking characteristics of auto-resonance are analyzed using an empirical mode decomposition of the scattered signal. This provides the intrinsic mode functions from which the associated instantaneous frequencies and phases can be determined. The Shannon entropy and the variance of the phase are used to quantify the behavior. Comparisons of the numerical results are made with current experimental data. [Support from NIH-EB006372 and NIH-2G12-RR003016121.]