12A-5 Subharmonic Response from Polymer-Shelled Contrast Agents

Current acoustic contrast agents are designed to be used in the low-MHz range (< 10 MHz) but there is a growing interest in using agents with high-frequency ultrasound (HFU, > 15 MHz). Polymer-shelled contrast agents represent the newest generation of agents and their HFU response has been relatively unexplored. Experiments were performed with polycaprolactone-shelled agents (POINT Biomedical, San Carlos, CA) having mean diameters 0.56, 1.1, and 3.4 mum. The agents were heavily diluted in water and passed through a flow system that permitted the backscatter from single agents to be digitized. The agents were exposed to 40 -MHz tone bursts of 1, 3, 5, 10, 15, and 20 cycles at peak-negative pressures of 0.6 to 6.3 MPa. At each exposure condition and with each contrast agent, 1000 valid single-bubble backscatter events were digitized and then analyzed for subharmonic content. The results showed that the likelihood of a subharmonic event increased as the number of cycles increased. All three agents had a subharmonic response for tone bursts of 10 to 20 cycles. A subharmonic was most likely at 3.9 MPa for the 3.4 mum agent and 1.7 MPa for the 0.56 and 1.1 mum agents. The results indicate that polymer-shelled agents have the potential to be used for HFU nonlinear imaging.