Polydisperse Versus Monodisperse Microbubbles: A Simulation Study for Contrast-Enhanced Ultrasound Imaging

Objective: 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 traditional polydisperse MBs with 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 using various-sized monodisperse MBs and their influence on non-linear imaging artifacts observed in traditional CEUS. Methods: 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 non-linear contrast source (INCS) method has previously demonstrated efficacy when simulating ultrasound propagation in large populations in which each bubble has individual properties and several orders of multiple scattering are significant. Therefore, this method is employed to realistically simulate both monodisperse and polydisperse MBs. Results: Our findings in CEUS imaging indicate that scattering from resonant monodisperse MBs is 11.8 dB stronger than scattering from polydisperse MBs. Furthermore, the amplitude of non-linear imaging artifacts downstream of the monodisperse population is 19.4 dB stronger compared with polydisperse suspension. Conclusion: Investigating the impact of multiple scattering on polydisperse populations compared with various monodisperse suspensions has revealed that monodisperse MBs are more effective contrast agents, especially when at resonance. Despite the strong signal-to-noise ratio of monodisperse populations, imaging artifacts caused by non-linear wave propagation are also enhanced, resulting in further mis-classification of MBs as tissue.