Frequency multiplexing ultrasound as a platform for enhanced harmonic imaging

In this research we developed an enhanced ultrasound (US) harmonic imaging (HI) method for the noninvasive imaging of microbubbles (MB). Lipid-based, gas-filled MB have been developed as contrast agents for US imaging. Their micron size makes them safe for intravenous injection, and they are widely used in the clinic for US imaging of blood vessels. MBs possess a non-linear response to an incident US field, enabling to separate their echoes from those generated by surrounding tissue via HI. Nevertheless, HI suffers from limitations in contrast, signal to noise ratio, generated artifacts and susceptibility to patients’ movement. We propose an enhanced HI method that is based on a recently discovered alternative MB non-linear effect, frequency mixing. This effect is triggered when a MB is excited simultaneously by multiple frequencies. Our unique transmit signal is the superposition of two frequencies transmitted in real time by a programmable US system. When a MB is excited by this waveform, new frequencies are generated only in the MB echoes and not in the tissue echoes, enabling their separation with high precision and sensitivity. The method can be implemented with conventional ultrasound systems, without the need for additional components.