The impact of monodisperse microbubble size on contrast-enhanced ultrasound super-localization imaging

Contrast-enhanced ultrasound (CEUS) super-localization imaging has shown promise for the assessment of microvascular networks by localizing and tracking microbubbles. The size of the available microbubbles for clinical use is polydisperse, but size-tailorable monodisperse microbubbles are now being developed that present a narrow size distribution. Therefore, proper frequency and pressure tuning have the potential to improve the signal-to-noise ratio and resolution of CEUS acquisitions, which can be expected to increase the performance of CEUS super-localization imaging. In this work, the impact of monodisperse microbubble size on CEUS imaging quality and the efficacy of super-localization imaging was investigated by jointly tuning different frequencies and pressures for different monodisperse microbubble size when performing in vitro CEUS imaging of microbubbles flowing through a dedicated sugar-printed dual-bifurcation microvasculature phantom. The obtained CEUS acquisitions were then post-processed to generate a super-localization output using the Gaussian-centroid localization approach. Four metrics, including generalized contrast-to-noise ratio, full-width half-maximum, number of localization events, and localization F1-score, were employed to quantify the CEUS imaging quality and super-localization performance. In general, jointly optimizing the transmit frequency and pressure for monodisperse microbubbles with smaller size leads to improved CEUS imaging and better super-localization performance. Yet, the weaker backscatter of smaller microbubbles must also be considered.