Inertial Cavitation-based Release Estimation - ICbRE

Cancer research increasingly focuses on local drug release in tumorous tissue by using drug carriers. Concurrently, techniques to quantify the associated drug release are under investigation. This study presents a Inertial Cavitation-based Release Estimation (ICbRE) method. The estimation is based on the assessment of inertial cavitation (IC) noise and its correlation to release data. To develop ICbRE, we used poly(lactic-co-glycolic acid) (PLGA) nanocapsules loaded with a fluorescent dye, which were flowed through a tissue-mimicking phantom, and exposed them to focused ultrasound bursts at 550-950 kHz with peak rarefaction pressures (PRP) of 0.22-1.85 MPa, corresponding to mechanical index (MI) values of 0.3-1.9. Cavitation activity was recorded using a passive cavitation detection (PCD) system. By training on acoustic data, we derived weight functions, interpreted as transfer functions, to solve this inverse problem. These weight functions were multiplied by a test set of the acoustic data to estimate payload release. The most accurate estimation showed an absolute error of 0.3% and a standard deviation of 1.9% from the nominal value. Given its precision, we propose the integration of ICbRE into focused ultrasound systems to estimate drug carriers' payload release. In the course of prospective cancer treatments, a drug's released payload may be simultaneously quantified while monitoring the cavitation noise to ensure an effective therapy.