Impact of Perfluoropentane Microdroplets Diameter and Concentration on Acoustic Droplet Vaporization Transition Efficiency and Oxygen Scavenging

Abstract

Acoustic droplet vaporization is the ultrasound-mediated phase change of liquid droplets into gas microbubbles. Following the phase change, oxygen diffuses from the surrounding fluid into the microbubble. An in vitro model was used to study the effects of droplet diameter, the presence of an ultrasound contrast agent, ultrasound duty cycle, and droplet concentration on the magnitude of oxygen scavenging in oxygenated deionized water. Perfluoropentane droplets were manufactured through a microfluidic approach at nominal diameters of 1, 3, 5, 7, 9, and 12 µm and studied at concentrations varying from 5.1 × 10^-5 to 6.3 × 10^-3 mL/mL. Droplets were exposed to an ultrasound transduced by an EkoSonic^TM catheter (2.35 MHz, 47 W, and duty cycles of 1.70%, 2.34%, or 3.79%). Oxygen scavenging and the total volume of perfluoropentane that phase-transitioned increased with droplet concentration. The ADV transition efficiency decreased with increasing droplet concentration. The increasing duty cycle resulted in statistically significant increases in oxygen scavenging for 1, 3, 5, and 7 µm droplets, although the increase was smaller than when the droplet diameter or concentration were increased. Under the ultrasound conditions tested, droplet diameter and concentration had the greatest impact on the amount of ADV and subsequent oxygen scavenging occurred, which should be considered when using ADV-mediated oxygen scavenging in therapeutic ultrasounds.

Keywords: cavitation; intravascular ultrasound; microfluidic emulsion manufacturing; perfluoropentane microdroplets; polydispersity; ultrasound contrast agent; ultrasound duty cycle.

Figure 1

Schematic of the in vitro flow phantom with black arrows showing direction of flow. Droplets were pumped from the sample reservoir and through the flow system maintained at 37 °C. The oxygenated water was saturated to a PO₂ of 560.8 ± 7.6 mmHg. Droplets were exposed to a 2.35 MHz-pulsed ultrasound using a 6 cm treatment zone EkoSonic^® catheter. The PO₂ in the fluid distal to the catheter was measured by a flow-through oxygen sensor. The effluent was collected to measure the size distribution and volume concentration of droplets that did not undergo ADV.

Figure 2

Normalized volume-weighted distribution for microfluidic droplets of nominal diameters 1, 3, 5, 7, 9, and 12 µm. The droplet production rate (droplets/s) is listed at the top of the figure for each droplet diameter. The colors (red, yellow, green, blue, violet, and magenta) used to plot the data correspond to nominal droplet diameters for each microdroplet (1, 3, 5, 7, 9, and 12 µm, respectively) and are used for all subsequent figures.

Figure 3

(a) The measured ADV transition efficiency without (white fill) and with (hatched fill) Lumason^® as a percentage of the change in the volume-weighted size distribution of the droplets with and without ADV. (b) The amount of oxygen scavenging with and without Lumason^®. The solid filled top of the stacked bar graph is the amount of oxygen scavenging observed peri-droplet (i.e., no ultrasound exposure, and thus, no ADV). The bottom portion of each bar describes the amount of oxygen scavenging observed peri-ADV without (white fill) and with (hatched fill) Lumason^®. The horizontal blue bar represents the initial PO₂ before droplets were infused, and thus, the maximum amount of PO₂ that could be scavenged. The error bars denote the standard deviation for five samples. The legend applies to both panels.

Figure 4

(a) ADV transition efficiency with burst periods of 0.450 ms (3.79% duty cycle), 0.725 ms (2.34% duty cycle), and 1.000 ms (1.70% duty cycle). The transition efficiency is calculated as a percent change based on the volume-weighted size distributions of the droplets. (b) The measured amount of oxygen scavenging peri-droplet (colored fill) or peri-ADV with burst periods of 0.450 ms, 0.725 ms, and 1.000 ms for droplets of 1, 3, 5, and 7 µm diameters. The horizontal blue bar represents the initial PO₂ before droplets were infused, and thus, the maximum amount of oxygen that could be scavenged. The error bars denote the standard deviation for five samples. The legend applies to both panels.

Figure 5

(a) ADV transition efficiency with pulse durations of 17.0 µs (1.70% duty cycle), 23.4 µs (2.34% duty cycle), and 37.9 µs (3.79% duty cycle). The transition efficiency is calculated as a percent change based on the volume-weighted size distributions of the droplets. (b) The measured amount of oxygen scavenging peri-droplet (colored fill) or peri-ADV with pulse durations of 17.0 µs, 23.4 µs, and 37.9 µs for droplets of 1, 3, 5, and 7 µm diameters. The horizontal blue bar represents the initial PO₂ before droplets were infused, and thus, the maximum amount of PO₂ that could be scavenged. The error bars denote the standard deviation for five samples. The legend applies to both panels.

Figure 6

(a) ADV transition efficiency for droplets of nominal diameters 3 (yellow), 5 (green), and 7 (blue) µm for initial droplet concentrations between 5.10 × 10⁻⁵ to 6.30 × 10⁻³ mL/mL without Lumason. The transition efficiency is calculated as a percent change based on the volume-weighted size distributions of the droplets. Individual measurements are denoted with diamonds. Lines are the moving average of the measurements with a period of 6. (b) The measured amount of oxygen scavenging for droplets of nominal diameters 3 (blue diamonds), 5 (green diamonds), and 7 (yellow diamonds) µm with corresponding lines representing moving averages. The horizontal blue bar represents the initial PO₂ before droplets were infused, and thus, the maximum amount of PO₂ that could be scavenged. The legend applies to both panels.

Figure 7

The measured amount of oxygen scavenged versus the modeled amount of oxygen scavenged for (a) trials investigating the impact of Lumason^®, (b) droplet concentration, (c) burst period, and (d) pulse duration. The legend at the top applies to all panels. Data points represent individual trials with the outer marker color indicating the nominal droplet diameter and the fill indicating the duty cycle, except in panel (a) where filled data points are from trials that used Lumason^® and open data points did not. The solid black line is a best-fit line based on the Pearson correlation analysis.