On the Prediction of the Subharmonic Threshold of an Ultrasound Contrast Agent

TL;DR

This paper presents a theoretical analysis of the subharmonic threshold in ultrasound contrast agents, explaining experimental observations through nonlinear resonance and damping effects, and examining the influence of shell parameters.

Contribution

It introduces an analytical method based on energy balancing and instability analysis to better understand subharmonic thresholds in UCAs, addressing previous experimental inconsistencies.

Findings

Subharmonic threshold depends on shell parameters and nonlinear resonance.

Amplitude-dependent nonlinear resonance explains low-pressure subharmonic shifts.

Nonspherical oscillations influence subharmonic emissions.

Abstract

Subharmonics emitted from microbubble-based ultrasound contrast agents (UCA) are considered as a noninvasive indicator for diagnostic applications in medical fields. Contrast ultrasound imaging using the modality of subharmonics could be also better than that of using harmonics. Unlike the harmonics of an UCA that increase with increasing the amplitude of excitation pressure, subharmonics occur only when the excitation pressure exceeds a threshold value. The excitation pressure inducing the onset of subharmonic components from the UCA during nonlinear oscillations is known as the subharmonic threshold. Although numerous studies on the subharmonics of free bubbles or UCAs have been carried out for decades, several experimental observations, such as the shift of the subharmonic resonance and subharmonic threshold at low excitation pressures, cannot be well characterized by existing theories. An analytical method for resolving these inconsistencies remains incomplete. The present article theoretically investigates the subharmonic threshold of an UCA through the techniques of energy balancing in the phase plane and instability analysis of subharmonic-free oscillations. The influence of shell parameters of the UCA on the subharmonic threshold is studied. Those experimental observations are explained by the amplitude-dependent nonlinear resonance and damping. The effect of nonspherical oscillations on subharmonic emissions is also discussed.