Impact of wavefront shape on nonlinear ultrasound imaging of monodisperse microbubbles

The field of contrast-enhanced ultrasound (CEUS) combines nonlinear, resonant microbubbles (MBs) with dedicated pulse sequences to reveal the vascular function of organs. Clinical ultrasound contrast agents consist of polydisperse MB suspensions with diameters ranging from 0.5 to 10 um and resonance frequencies ranging from 1 to 15 MHz. As a result, just a small fraction of MBs resonates at a given ultrasound frequency. MB suspensions with narrow size distributions can be tuned for a specific imaging frequency, boost CEUS sensitivity and enable deeper vascular imaging. However, their enhanced nonlinear behavior makes imaging susceptible to nonlinear wave propagation artifacts. Here, we numerically investigate the impact of the acoustic wavefront shape on the imaging of nonlinear, monodisperse MBs. Specifically, our approach relies on an extension of the Iterative Nonlinear Contrast Source (INCS) method that accounts for all nonlinear effects in CEUS. We demonstrate that supersonic x-shaped wavefronts referred to as x-waves can be used to generate ultrasound images of monodisperse MBs without nonlinear wave propagation artifacts. On the contrary, imaging based on focused, planar and diverging wavefronts leads to significant nonlinear artifacts. Taken together, our results show that x-waves can harness the full potential of monodisperse MBs by enabling their sensitive and specific detection in a tissue context.