Non-linear Response and Viscoelastic Properties of Lipid-Coated Microbubbles: DSPC versus DPPC

Abstract

For successful in vivo contrast-enhanced ultrasound imaging (CEUS) and ultrasound molecular imaging, detailed knowledge of stability and acoustical properties of the microbubbles is essential. Here, we compare these aspects of lipid-coated microbubbles that have either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as their main lipid; the other components were identical. The microbubbles were investigated in vitro over the frequency range 1–4 MHz at pressures between 10 and 100 kPa, and their response to the applied ultrasound was recorded using ultrahigh-speed imaging (15 Mfps). Relative to DPPC-coated microbubbles, DSPC-coated microbubbles had (i) higher acoustical stability; (ii) higher shell elasticity as derived using the Marmottant model (DSPC: 0.26 ± 0.13 N/m, DPPC: 0.06 ± 0.06 N/m); (iii) pressure amplitudes twice as high at the second harmonic frequency; and (iv) a smaller amount of microbubbles that responded at the subharmonic frequency. Because of their higher acoustical stability and higher non-linear response, DSPC-coated microbubbles may be more suitable for contrast-enhanced ultrasound.