Investigating the resonance response of a system of two ultrasound-driven lipid encapsulated microbubbles

Abstract

Ultrasound-stimulated microbubbles are clinical imaging agents and being developed for therapeutic applications. Here, we aim to understand the behaviour of two individual phospholipid-encapsulated microbubbles in close proximity to each other, typically the case given clinical doses. We developed a finite element model to study the radial resonance response of each microbubble within a two-microbubble system from 1–8 MHz with bubble diameters ranging from 2 to 4 μm, bubble center-to-center distances h = 8–24 μm, and peak-negative pressures of 30–45 kPa. For two identical microbubbles, our results show the frequency of maximum response (fMR) decreases (7%–10%) and the amplitude of maximum response (AMR) increases (9%–11%) as the microbubbles approach one another. For a two-bubble system of different microbubble sizes, the larger microbubble shows no change in fMR and a slight shift of AMR (2–3%). However, the smaller microbubble exhibits an increase in fMR (7–11%) and a significant decrease of AMR (38–52%). Furthermore, when in very close proximity (h = 8 μm), smaller bubbles exhibit a secondary resonance peak corresponding to the fMR of the larger bubble with amplitudes comparable to its primary resonance peak. Our work suggests that microbubble resonance behaviour is greatly affected by the presence of nearby bubbles, which has implications in imaging and therapy.