Polydisperse versus monodisperse microbubbles: A simulation study for contrast-enhanced ultrasound imaging

Contrast-enhanced ultrasound (CEUS) presents distinct advantages in diagnostic echography. Utilizing microbubbles (MBs) as conventional contrast agents enhances vascular visualization and organ perfusion, facilitating real-time, non-invasive procedures. There is a current tendency to replace the traditional polydisperse MBs by novel monodisperse formulations in an attempt to optimize contrast enhancement and guarantee consistent behavior and reliable imaging outcomes. This study investigates the contrast enhancement achieved by monodisperse MBs of different sizes, and their influence on nonlinear imaging artifacts observed in traditional CEUS. To explore the differences between monodisperse and polydisperse populations without excessive experimentation, numerical simulations are employed for delivering precise, objective and expeditious results. The Iterative Nonlinear Contrast Source (INCS) method has previously demonstrated its efficacy in simulating ultrasound propagation in large populations in which each bubble has individual properties and several orders of multiple scattering are significant. Our findings in CEUS imaging indicate that scattering from resonant monodisperse microbubbles is 11.8 dB stronger than scattering from the polydisperse population. Furthermore, the amplitude of nonlinear imaging artifacts downstream of the monodisperse population is 19.4 dB stronger compared to polydisperse suspension. Investigating the impact of multiple scattering on polydisperse populations compared to various monodisperse suspensions reveals that monodisperse MBs are more effective contrast agents, especially when on resonance. Despite the strong signal to noise ratio of monodisperse populations, the imaging artifacts due to nonlinear wave propagation are also enhanced, resulting in more missclassification of MBs as tissue.