Our ability to study microbubble dynamics in vivo and link them to distinct mechano-biological effects hinges on our ability to accurately estimate the temporal changes in MB radius during ultrasonic excitation. Here, we hypothesize that real-time passive cavitation detection (PCD) monitoring combined with linear acoustic wave propagation theory can accurately estimate stable MB radius dynamics under in vivo conditions. To test our hypothesis, we employed numerical simulations, based on Rayleigh–Plesset modeling, followed by experimental validation, using calibrated PCDs with concurrent optical imaging of MB dynamics using high frame rate microscopy. Our method termed linear acoustic wave propagation and superposition (LAWPS) algorithm, combines Fourier series expansion with Euler’s relationship to estimate the acoustic emission (AE) from single MB, which is considered as a monopole source (i.e., R0 + ΔR < λ). LAWPS algorithm, which is independent of MB properties and, thus, can be linearly reversed to calculate MB oscillation radius from AE, was able to accurately capture the radiated pressure generated from a Rayleigh–Plesset MB modeling. Crucially, inverse LAWPS algorithm onto AE generated by Vokurka et al. resulted in the original MB model. Experimental observation using monodisperse MBs was able to accurately estimate the temporal changes in MB radius during 0.5 MHz ultrasonic excitation
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