The "quasi-stable" lipid shelled microbubble in response to consecutive ultrasound pulses

Controlled microbubble stability upon exposure to consecutive ultrasound exposures is important for increased sensitivity in contrast enhanced ultrasound diagnostics and manipulation for localised drug release. An ultra high-speed camera operating at 13 × 10 6 frames per second is used to show that a physical instability in the encapsulating lipid shell can be promoted by ultrasound, causing loss of shell material that depends on the characteristics of the microbubble motion. This leads to well characterized disruption, and microbubbles follow an irreversible trajectory through the resonance peak, causing the evolution of specific microbubble spectral signatures. © 2012 American Institute of Physics

Modeling atomic force microscopy and shell mechanical properties estimation of coated microbubbles

We present an extensive comparison with experimental data of our theoretical/numerical model for the static response of coated microbubbles (MBs) subject to compression from an atomic force microscope (afm). The mechanics of the MB's coating is described in the context of elastic thin shell theory. The encapsulated fluid is treated as compressible/incompressible pertaining to a gas/liquid, while the thinning of the liquid film between the MB and the afm cantilever is modeled via introduction of an interaction potential and the resulting disjoining pressure. As the external force increases, the experimental force-deformation (f-d) curves of MBs covered with polymer have an initial linear response (Reissner regime), followed by a non-linear curved downwards response (Pogorelov regime) where buckling takes place. On the other hand, the f-d curve for MBs covered with lipid monolayers initially follows the Reissner regime, but buckling is bypassed to a curved upwards regime where internal gas pressure dominates. The elastic properties, namely Young's modulus and shell thickness, for MB's covered with polymer can be estimated by combining the buckling point and the slope of the Reissner regime or the slopes of Reissner and Pogorelov regimes. Comparison of the present model with afm f-d curves for polymer shows satisfactory agreement. The area dilatation and bending moduli are shown to be the appropriate independent elastic parameters of MBs covered with phospholipid monolayers and are estimated by combination of the transition from Reissner to pressure dominated regime. Simulations and experiments in this case are in excellent agreement

The effect of resonance on transient microbubble acoustic response: Experimental observations and numerical simulations

A large number of acoustic signals from single lipid-shelled Definity® (Lantheus Medical Imaging, N. Billerica, MA) microbubbles have been measured using a calibrated microacoustic system, and a unique transient characteristic of resonance has been identified in the onset of scatter. Comparison of the numerically obtained response of microbubbles with acoustic measurements provides good agreement for a soft shell that is characterized by small area dilatation modulus and strain softening behavior, and identifies time to maximum radial excursion and scatter as a robust marker of resonance during transient response. As the sound amplitude increases a two-population pattern emerges in the time delay vs the fundamental acoustic scatter plots, consisting of an initial part pertaining to microbubbles with less than resonant rest radii, which corresponds to the weaker second harmonic resonance, and the dominant resonant envelope pertaining to microbubbles with resonant and greater than resonant rest radii, which corresponds to the primary and subharmonic resonances. Consequently, a wider resonant spectrum is observed. It is a result of the strain softening nature of soft lipid shells, based on which the microbubble sizes corresponding to the above resonances decrease as the sound amplitude increases. This bares an impact on the selection of an optimal microbubble size pertaining to subharmonic imaging. © 2018 Acoustical Society of America

The effect of resonance on transient microbubble response; Response; experimental and theoretical observations

Nonlinear microbubble oscillations can be exploited by signal processing to provide contrast enhancement in ultrasound imaging. High-speed optical investigations have established that microbubbles resonate in-vitro, but resonance has not yet been established in-vivo. Here we aim to establish the acoustic signature of resonance, which will help identify its occurrence in-vivo and further optimize microbubble signal processing. Resonant microbubbles provide a transient acoustic amplitude response, which is a signature unique to resonance. Large numbers of acoustic signals from single lipid-shelled Definity® microbubbles have been measured using a calibrated microacoustic system and a unique transient characteristic of resonance has been identified in the onset of scatter. We present theoretical results based on the Mooney-Rivlin strain softening shell model to show that for realistic shell parameters pulse durations longer than those routinely used in clinical imaging pulses are required to reach a steady state microbubble resonance, indicating the majority of contrast enhancement arises from off-primary resonance microbubble scatter. The specificity of this response may generate higher sensitivity signal processing algorithms, and this should be investigated in the future in realistic vessel sizes to address in vivo requirements. © 2012 IEEE