State of the art on microbubble cavitation monitoring and feedback control for blood-brain-barrier opening using focused ultrasound

Focused ultrasound is a non-invasive and highly promising method for targeted and reversible blood-brain barrier permeabilization. Numerous preclinical studies aim to optimize this localized drug delivery method in rodents and non-human primates. A few clinical trials have been initiated to treat various brain diseases in humans using simultaneous BBB permeabilization and drug injection. This review presents the state of the art of in vitro and in vivo cavitation control algorithms for BBB permeabilization using microbubbles and focused ultrasound. First, we described the different cavitation states, their physical significance in terms of microbubble behavior and their translation into the spectral composition of the backscattered signal. Then, we reported the different indexes calculated and used during the ultrasonic monitoring of cavitation. Finally, the different in vitro and in vivo cavitation control strategies described in the literature are presented and compared.