Broadband Attenuation and Size Measurements of Ultrasound Contrast Agents

Abstract

Echogenic liposomes (ELIP) are under development as an ultrasound contrast agent (UCA) for image-guided, targeted drug delivery. The aim of this study was to investigate the effect of the lipid formulation and type of encapsulated gas on the acoustic response of ELIP under physiologic conditions. The influence of temperature and diluent on the measured attenuation coefficients was investigated for ELIP as well as the commercial lipid-based UCA Definity. Broadband attenuation spectra were obtained for agents diluted either in whole blood or in saline solution containing 0.5% bovine serum albumin (BSA) at 25°C and 37°C. The spectra and particle size distributions obtained using a Coulter counter were compared with scattering theory to estimate the properties of the lipid shell stabilizing the microbubbles. Dilution of ELIP or Definity in either whole blood or BSA solution did not affect the measured attenuation coefficients. However, the temperature and gas saturation of the diluent were found to impact the attenuation spectra significantly. The attenuation spectra of UCAs are strongly impacted by temperature and gas saturation relative to physiologic values. Knowledge of the acoustic properties and size distribution of these agents under physiologic conditions will allow for their safe use in vivo.