Nonlinear imaging of targeted microbubbles with intravascular ultrasound

The nonlinear detection of targeted microbubbles at high ultrasound frequencies was investigated. A prototype nonlinear intravascular ultrasound (IVUS) system was employed using a 20 MHz fundamental frequency (F20) to examine 40 MHz second harmonic (H40) signals and a 40 MHz fundamental frequency (F40) to examine 20 MHz subharmonic (SH20) signals. An experimental biotinated micron to submicron lipid encapsulated agent was targeted to avidin coated agar-based tissue mimicking phantoms. An examination of bound bubble acoustic signatures demonstrated the feasibility of initiating H40 and SH20 signals. Imaging experiments showed improvements in contrast-to-tissue ratios (CTR) using both H40 and SH20 relative to fundamental frequency imaging. These results indicate the potential of high frequency nonlinear imaging as a means of improving the detection of targeted microbubbles.