Impact of temperature on the size distribution and shell properties of ultrasound contrast agents

Abstract

Physical characterization of ultrasound contrast agents (UCAs) is important for their efficacious use in theragnostic applications. The goal of this study was to elucidate the impact of temperature on the size distribution and shell properties of Definity®, an FDA-approved clinical UCA. A Coulter counter (Multisizer IV) was modified to enable size measurements of UCAs at elevated temperatures. The size distribution and attenuation spectrum of Definity® was measured at room temperature (25 °C) and physiological temperature (37 °C), and used to estimate the shell stiffness and viscosity of the agent at both temperatures. The attenuation coefficient of Definity® increased by as much as 5 dB at 37 °C relative to 25 °C. The highest increase in attenuation was observed at 10 MHz, the resonance frequency of Definity®. However, no significant difference was observed in the size distribution of Definity® at 25 °C and 37 °C. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10-6 ± 0.07 × 10-6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10-6 ± 0.04 × 10-6 kg/s at 37 °C. These results indicate that the change in shell properties mediates the change in acoustic behavior of Definity® at physiological temperature.