Characterization of microbubble contrast agents for echographic imaging through time-scheduled size distribution measurements

Aim of this work was to study the dissolution behaviour of the phospholipid-shelled perfluorobutane microbubbles of an experimental contrast agent for echographic imaging through an innovative methodology based on time-scheduled size distribution measurements. Two different contrast handling procedures were employed and temporal evolution of corresponding microbubble populations was monitored for several hours. Dissolution behaviour of shelled microbubbles resulted to be qualitatively analogous to that theoretically predicted for unshelled perfluorobutane bubbles, with a much longer lifetime due to the shell effect. In particular, mean microbubble diameter, initially around 2 ?m, first increased to more than 2.6 ?m and then gradually reduced to less than 1.7 ?m, with corresponding variations of the effectively employable ultrasound frequencies for imaging purposes. We also demonstrated that excess lipid material is diffused as submicron particle shedding. Finally, we discussed the implications of these results for diagnostic and therapeutic applications involving the studied microbubbles.