Experimental and theoretical studies of microbubble interaction with tissue help optimize drug delivery and imaging.

Abstract

A multi‐disciplinary approach is required to engineer ultrasound contrast agents for drug delivery and imaging. These micrometer‐sized bubbles oscillate in response to acoustic energy, emitting non‐linear echoes that can be differentiated from the tissue when imaged. If large enough, the oscillations generate perturbations capable of affecting the region surrounding the bubble. Here, microbubble activity is observed in scenarios that mimic those found in vivo to provide intuition about the mechanisms for contrast‐enhanced imaging and drug delivery. High‐speed imaging of microbubble oscillation at 1 MHz within ex vivo vessels reveals that microbubble expansion is significantly reduced, and the constrained oscillation imparts a force capable of displacing the surrounding vessel wall. [Caskey et al., 122, 1191‐1200.] Bubble oscillation near a tissue‐mimicking gel boundary shows fluid jets impinging on and disrupting the gel surface at 1, 2.25, and 5 MHz. [Caskey et al., 125, EL183–EL189.] The bubble concentration and acoustic parameters associated with gel disruption and vessel displacement are examined with respect to theoretical predictions, suggesting the ratio of pressure to frequency may be a good indicator for these phenomena. Finally, we also report on extensions of this work to the interaction of targeted contrast agents with tissue.