Non-linear response and viscoelastic properties of lipid-coated microbubbles: DSPC versus DPPC

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.