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            <title xml:lang="en">Fragmentation thresholds simulated for antibubbles with various infinitesimal elastic shells</title>
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            <funder>National Research Foundation of South Africa, Grant Number 127102</funder>
            <funder>Academy of Finland, Grant Number 340026</funder>
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                <title xml:lang="en">Fragmentation thresholds simulated for antibubbles with various infinitesimal elastic shells</title>
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                <title level="j">Current Directions in Biomedical Engineering</title>
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                  <biblScope unit="volume">8</biblScope>
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                <term xml:lang="en">Acoustic fragmentation</term>
                <term xml:lang="en">ultrasound contrast agent</term>
                <term xml:lang="en">shell stiffness</term>
                <term xml:lang="en">antibubble oscillation modelling</term>
                <term xml:lang="en">Rayleigh-Plesset equation</term>
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              <p>Antibubbles are small gas bubbles comprising one or multiple liquid or solid cores, typically surrounded by stabilising shells. Acoustically active microscopic antibubbles have been proposed for use as theranostic agents. For clinical applications such as ultrasound-guided drug delivery and flash-echo, it is relevant to know the fragmentation threshold of antibubbles and the influence of the stabilising shells thereon. For antibubbles with an infinitesimal frictionless elastic shell of constant surface tension, we simulated ultrasound-assisted fragmentation by computing radial pulsation as a function of time using an adapted Rayleigh-Plesset equation, and converting the solutions to time-variant kinetic energy of the shell and time-variant surface energy deficit. By repetition over a range of pressure amplitudes, fragmentation thresholds were found for antibubbles of varying size, core volume, shell stiffness, and driving frequency. As backscattering increases with scatterer size, and as drug delivery would require vehicles just small enough to pass through capillaries with a relatively large payload, we chose to present typical results for antibubbles of resting diameter 6 $\mu$m with a 90% incompressible core. At a driving frequency of 13 MHz, the fragmentation threshold was found to correspond to a mechanical indices less than 0.4, irrespective of shell stiffness. This mechanical index is not considered unsafe in diagnosis. That means that antibubbles acting as drug-carrying vehicles could release their payload under diagnostic conditions.</p>
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