Thermal response of contrast agent microbubbles: preliminary results from physico-chemical and US-imaging characterization.

Hyperthermia (HT) is a therapeutic strategy based on the selective damaging of tumoral cells when heated at temperatures in the range 41-45 degrees C. We are currently investigating the feasibility of Ultrasound (US) imaging to perform a non-invasive, efficient and cost effective temperature monitoring of heated tissues. Commercial US contrast agents (Sonovue, Bracco), consisting in microbubbles of SF(6) coated with a phospholipidic shell, greatly improve the US echo signal from tissues. Further investigations have been performed, consisting in physico-chemical and US-imaging characterization. In conclusion, we demonstrate that Sonovue microbubbles reach their maximal diameter at 40 degrees C, and then a sharp decrease is observed, possible due to the occurrence of gel-sol transition of the phospholipidic shell. At the same temperature the maximal backscattering intensity is predicted and actually experimentally observed. Sonovue, as well as other contrast agents based only on phospholipids, are, therefore, not suitable for use as non-invasive temperature monitoring medium since it is sensitive to temperatures below the hyperthermic range. Although microbubbles are in principle thermally effective, other coating materials should be investigated in order to increase their operative thermal range.