Pharmacokinetic Modeling of the Second-Wave Phenomenon in Nanobubble-Based Contrast-Enhanced Ultrasound

With a typical 100-500 nm diameter, nanobubbles are a promising new-generation ultrasound contrast agent that paves ways for several applications, such as efficient drug delivery, molecular imaging, and assessment of vascular permeability. Due to their unique physical properties, nanobubbles exhibit distinct in vivo pharmacokinetics. We have shown that the first pass of the nanobubble bolus is usually accompanied by the appearance of a second bolus (wave) within a time range of about 15 minutes. Such phenomenon, to the best of our knowledge, has never been observed with conventional microbubbles and smaller molecular contrast agents used in MRI and CT. In a previous study, we showed the potential of this phenomenon in supporting cancer diagnosis. This study focuses on developing a new compartmental pharmacokinetic model that can be used to interpret the second-wave phenomenon. With this model, we can analyze more in-depth the roles of several physiological factors affecting the characteristics of the second-wave phenomenon.

Automated summary

Nanobubbles, with their unique physical properties, have shown potential as a new generation ultrasound contrast agent for various applications. The appearance of a second bolus (wave) following the first pass of nanobubbles has been observed, which is not seen with conventional microbubbles and molecular contrast agents. This study aims to develop a new compartmental pharmacokinetic model to analyze the roles of physiological factors in the characteristics of the second-wave phenomenon.