(G-275) Vaporization kinetics of endoskeletal droplets for contrast-enhanced ultrasound

Introduction:: Vaporizable droplets describe a class of liquid emulsions which transition from a liquid droplet to a gas bubble upon exposure to an energy source, such as direct heating, ultrasound, or light absorbance [1-3]. These droplets have been a focus of research as contrast agents in ultrasound imaging and therapeutics, especially when imaging of the extravascular space is desired [4]. In the design of vaporizable droplets for ultrasound, volatile perfluorocarbon (n-C3F8, n-C4F10) droplets have been commonly employed, since they benefit from vaporizing at lower energy sources. However, these species suffer from decreased colloidal stability in water. In contrast, less volatile perfluorocarbons, like perfluoropentane, are more difficult to vaporize but have improved stability.

Vaporizable endoskeletal droplets (VEDs) are a type of vaporizable droplet consisting of a solid hydrocarbon (HC) core encapsulated by liquid perfluoropentane (FC) (Figure 1A) [5]. Upon heating, the HC core melts and interfacial mixing between the phases occurs. This disrupts the intermolecular cohesion between the FC molecules, lowers the limit of thermal stability, and causes vaporization. Through this mechanism, the temperature of vaporization can be tuned by selecting an appropriate hydrocarbon chain length. To better understand the energy required to vaporize the droplets during ultrasound imaging, we aim to determine the activation energy through the analysis of their vaporization kinetics and the application of the Arrhenius equation.


Materials and Methods:: Polydisperse VEDs with a solid eicosane (n-C20H42) core and liquid perfluropentane (n-C5F12) were prepared utilizing a shaking technique. Size distributions and concentrations were found using a Multisizer III Coulter Counter (Beckman Coulter). To enhance the number of vaporizations, the droplets were heat treated by immersing them in a hot bath set to 45°C for 5 mins, then quenched in an ice bath for an additional 5 mins.

Using a heating stage positioned on a microscope, droplets were heated and vaporization events were recorded over a range of temperatures. The data was normalized and the vaporization temperature was calculated, defined as the temperature where 50% of the microbubbles have formed. Additionally, the temperature where 25% and 75% of the microbubbles had formed was calculated to determine a range of temperatures over which the droplets vaporize. The droplets were then heated to a constant temperature and the rate of microbubble formation was recorded. This was done for four different temperatures, derived from the heating curve. At each temperature, the vaporization rate constant (k) was determined by assuming first-order kinetics. Using the vaporization rate constants, the apparent activation energy for vaporization was determined from an Arrhenius plot (ln(k) vs T^-1), where the activation energy is the negative product of the slope and the ideal gas constant.


Results, Conclusions, and Discussions:: The mean (± standard deviation) diameter of the droplets was measured to be 1.76 ± 1.11 μm, where the size distribution is shown in Figure 1B. From the vaporization curve, the vaporization temperature was calculated to be 32.0 ± 0.9 °C, while the 25% and 75% vaporization temperatures were calculated as 30.7 ± 1.6 °C and 32.8 ± 0.5 °C, respectively (Figure 1C). The vaporization rate constants are 3.31 ± 0.59 x 10-9, 2.96 ± 1.31 x 10-9, 4.73 ± 0.65 x 10-9, and 10.06 ± 5.26 x 10-9 mL-1 s-1 for T = 30, 31, 32, and 33 °C. Using these rate constants, an activation energy of 304.7 kJ mol-1 was calculated from the slope of the Arrhenius plot (Figure 1D).

These preliminary results provide a methodology to calculate the activation energy for the vaporization of endoskeletal droplets. This activation energy can be used to develop theoretical models that predict the behavior of the droplets when being exposed to different energy sources, supporting their future application in imaging and therapeutics. Based on previous observations of the vaporization behavior, the activation energy will likely vary based on HC chain length, the ratio of HC and FC, and the size of the droplet [6]. By understanding the activation energy for different formulations, we can better optimize vaporizable endoskeletal droplets as ultrasound contrast agents.


Acknowledgements (Optional): :

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