Phase shift liquid perfluorocarbon (PFC) droplets vaporizable by ultrasound into echogenic microbubble above a threshold pressure, termed acoustic droplet vaporization (ADV), are used for therapeutic and diagnostic applications. This study systematically investigated the effect of excitation frequency (2.25, 10, and 15 MHz) on the ADV and inertial cavitation (IC) thresholds of lipid-coated PFC droplets of three different liquid cores-perfluoropentane (PFP), perfluorohexane (PFH), and perfluorooctyl bromide (PFOB)-and of two different sizes-average diameters smaller than 3 lm and larger than 10 lm-in a tubeless setup. This study found that the ADV threshold increases with frequency for the lowest boiling point liquid, PFP, for both large and small size droplets. For higher boiling point liquids, PFH and PFOB, this study did not detect vaporization for small size droplets at the excitation levels (maximum 4 MPa peak negative) studied here. The large PFOB droplets experienced ADV only at the highest excitation frequency 15 MHz. For large PFH droplets, ADV threshold decreases with frequency that could possibly be due to the superharmonic focusing being a significant effect at larger sizes and the higher excitation pressures. ADV thresholds at all the frequencies studied here occurred at lower rarefactional pressures than IC thresholds indicating that phase transition precedes inertial cavitation. V

Phase shift droplets vaporizable by acoustic stimulation offer the advantages of producing microbubbles as contrast agents in situ as well as higher stability and the possibility of achieving smaller sizes. Here, the acoustic droplet vaporization (ADV) threshold of a suspension of droplets with a perfluoropentane (PFP) core (diameter 400-3000 nm) is acoustically measured as a function of the excitation frequency in a tubeless setup at room temperature. The changes in scattered responses-fundamental, sub-, and second harmonic-are investigated, a quantitative criterion is used to determine the ADV phenomenon, and findings are discussed. The average threshold obtained using three different scattered components increases with frequency-1.05 ± 0.28 MPa at 2.25 MHz, 1.89 ± 0.57 MPa at 5 MHz, and 2.34 ± 0.014 MPa at 10 MHz. The scattered response from vaporized droplets was also found to qualitatively match with that from an independently prepared lipid-coated microbubble suspension in magnitude as well as trends above the determined ADV threshold value.

Echogenic liposomes (ELIPs) are an excellent candidate for ultrasound activated therapeutics and imaging. Although multiple experiments have established their echogenicity, the underlying mechanism has remained unknown. However, freeze-drying in the presence of mannitol during ELIP preparation has proved critical to ensuring echogenicity. Here, the role of this key component in the preparation protocol was investigated by measuring scattering from freshly prepared freeze-dried aqueous solution of mannitol-and a number of other excipients commonly used in lyophilization-directly dispersed in water without any lipids in the experiment. Mannitol, meso-erythritol, glycine, and glucose that form a highly porous crystalline phase upon freeze-drying generated bubbles resulting in strong echoes during their dissolution. On the other hand, sucrose, trehalose, and xylitol, which become glassy while freeze-dried, did not. Freeze-dried mannitol and other crystalline substances, if thawed before being introduced into the scattering volume, did not produce echogenicity, as they lost their crystallinity in the thawed state. The echogenicity disappeared in a degassed environment. Higher amounts of sugar in the original aqueous solution before freeze-drying resulted in higher echogenicity because of the stronger supersaturation and crystallinity. The bubbles created by the freeze-dried mannitol in the ELIP formulation play a critical role in making ELIPs echogenic.

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Ultrasound contrast microbubbles experience widely varying ambient blood pressure in different organs, which can also change due to diseases. Pressure change can alter the material properties of the encapsulation of these microbubbles. Here the characteristic rheological parameters of contrast agent Definity are determined by varying the ambient pressure (in a physiologically relevant range 0-200 mm Hg). Four different interfacial rheological models are used to characterize the microbubbles. Effects of gas diffusion under excess ambient pressure are investigated in detail accounting for size decrease of contrast microbubbles. Definity contrast agent show a change in their interfacial dilatational viscosity (3.6 × 10(-8) Ns/m at 0 mm Hg to 4.45 × 10(-8) Ns/m at 200 mm Hg) and interfacial dilatational elasticity (0.86 N/m at 0 mm Hg to 1.06 N/m at 200 mm Hg) with ambient pressure increase. The increase results from material consolidation, similar to such enhancement in bulk properties under pressure. The model that accounts for enhancement in material properties with increasing ambient pressure matches with experimentally measured subharmonic response as a function of ambient pressure, while assuming constant material parameters does not.