A dose-efficient treatment strategy for histotripsy by removing cavitation memory

Cavitation memory effect occurs when fragments of cavitation bubbles persist in the host medium and act as seeds for subsequent events. In pulsed cavitational ultrasound therapy, or histotripsy, this effect may cause cavitation to repeatedly occur at these seeded locations, producing inhomogeneous lesions or requiring excess pulses to completely homogenize the target volume. We hypothesized that by removing the memory, the cavitation bubbles could be induced at random locations in response to each pulse, leading to complete and homogeneous disruption of the target volume with fewer pulses. To test the hypothesis, the cavitation memory was passively removed by increasing the time intervals between successive pulses, Δt. The cavitation patterns and the lesion development process using various Δt´s were studied. Results showed an exponential decrease in the similarity between the spatial distributions of cavitation bubbles in successive pulses with increasing Δt´s; correspondingly, the lesion was completely and homogeneously fractionated with significantly fewer pulses for longer Δt´s. These results indicated that the removal of the cavitation memory may produce more dose-efficient treatments and homogeneous lesions.