Bidimensional Multiscale Entropy for Monitoring the Dynamics of Droplet Fragmentation under Ultrasound Stimulation

Real-time monitoring of perfluorocarbon droplet vaporization under ultrasound stimulation is a crucial step for optimizing their therapeutic clinical applications. This study introduces a novel quantitative metric, named bidimensional multiscale entropy (BMSE), designed to monitor droplet fragmentation dynamics in real-time. BMSE was computed from radio frequency data acquired using a clinical ultrasound probe operating in the 7.5-15 MHz frequency range and it provided valuable insights into droplet behavior under diverse acoustic conditions. Our findings revealed that droplet fragmentation is highly sensitive to acoustic parameters, with the most significant effects observed at 38 kHz and 100 kPa. This work demonstrates for the first time that the BMSE metric enables an accurate real-time analysis, offering crucial feedback for precise control over droplet fragmentation, such as in drug release processes.Clinical Relevance— This work introduces a novel quantitative metric for detecting perfluorocarbon droplet fragmentation dynamics under ultrasound stimulation. Such an approach promises to enhance ultrasound-mediated drug delivery by enabling real-time monitoring capabilities, leading to more precise, controlled and effective therapeutic applications.