Radiation force-enhanced targeted imaging and near real-time molecular imaging using a dual-frequency high-resolution transducer: In-vitro and in-vivo results

Recently, there has been an interest in the application of radiation force to enhance the adhesion and detection of targeted contrast agents and concentrate therapeutic delivery vehicles. This is of particular interest for small animal studies, where much of the work on ultrasonic molecular imaging and therapeutic delivery are being tested. The magnitude of radiation force on ultrasound contrast agents is maximized near the bubbles´ resonance frequency. Additionally, optimal radiation force delivery involves high duty cycles at non-destructive pressures. Thus, traditional high-frequency imaging transducers are not optimized to produce radiation force on most microbubble contrast agents. Our motivation was to design a dual-frequency high-resolution ultrasound probe for radiation-force enhanced targeted imaging in small animal studies. A prototype dual-frequency confocal transducer has been developed and tested with a commercial high-frequency imaging system. This probe enables generation of radiation force pulses in the frequency range of 2-4 MHz with simultaneous imaging at 30 MHz. We present radiation-force enhanced targeting data in-vitro and in-vivo. Molecular imaging of angiogenesis in a rodent model benefits from a 7 fold increase in signal intensity after radiation-force enhanced targeting compared to standard rheologically-mediated targeting. We demonstrate capability of near real-time detection of targeted contrast agents in-vitro using radiation force to mediate adhesion followed by slow-time filtering to separate free and targeted contrast agent signal.