Non-invasive homogeneous targeted blood-brain barrier disruption using acoustic holography with a clinical focused ultrasound system

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a 1024-element phased array transducer. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each elements phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz hemispherical transducer being tested clinically to enhance drug delivery via blood-brain barrier disruption. The holograms were evaluated in a tissue-mimicking phantom and in vivo in experiments disrupting the blood-brain barrier in rats and in a macaque. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density. TeaserHolography can shape the focal region of a clinical focused ultrasound system developed for targeted drug delivery in the brain.