Ultrasound Frequency Mixing for Enhanced Contrast Harmonic Imaging of Microbubbles.

Microbubbles (MBs) serve as contrast agents in diagnostic ultrasound (US) imaging. Contrast harmonic imaging (CHI) of MBs takes advantage of their nonlinear properties that generate additional harmonic frequencies in the received spectrum. However, CHI suffers from limitations in terms of contrast, the signal-to-noise ratio, and artifacts. This article presents an enhanced, real-time, nonlinear imaging technique based on the excitation of MBs with a dual frequency waveform. The MBs trigger a frequency mixing effect that generates additional frequency components in the received spectrum; i.e., difference and sum frequencies, in addition to the standard harmonics, thus amplifying the MB's nonlinear response and enhancing image contrast. In this real-time approach, two single frequency waveforms are superpositioned into a dual frequency transmission. The dual frequency waveform is incorporated into a standard pulse-inversion (PI) sequence and is transmitted by an array transducer using an arbitrary waveform generator (AWG) in a programmable US system. Upon receive, standard dynamic receive beamforming is used, without additional post processing. Numerical simulations using the Marmottant model are used to confirm the generation of the difference frequency in the MB's backscattered echoes. The resulting image quality enhancement is demonstrated in a tissue-mimicking phantom containing MBs' suspension. A maximal contrast improvement of 3.43 dB compared to standard PI was achieved, along with a reduction by 4.5 fold in the mechanical index (MI).