Development of efficient method of generating reactive oxygen species by expanding cavitation region using ultrasound focus scanning in the direction of ultrasound propagation

Abstract

Sonodynamic therapy (SDT) is a minimally invasive high-intensity focused ultrasound (HIFU) based therapy that combines a sonosensitizer and reactive oxygen species (ROS), which are produced by acoustic cavitation. In this paper, we experimentally examined the effectiveness of a proposed method of scanning the ultrasound focus in the direction of HIFU propagation for continuously generating cavitation clouds to expand the region of ROS generation and increase the amount of ROS. First, the continuous generation of cavitation bubbles was observed using a high-speed camera, and it was confirmed that bubbles could be generated even with a short-duration HIFU, which is difficult to generate bubbles by itself. Subsequently, we evaluated the area and amount of ROS generation by imaging sonochemiluminescence. Comparing the irradiation at 1 point with that at 7 points, the amount of ROS per acoustic energy increased by about 1.5 times, suggesting that it is an efficient method for ROS generation.

Expansion of the cavitation region using ultrasound focus scanning in the direction of ultrasound propagation for an efficient method of histotripsy

“…Therefore, it was found that bubble clouds can be generated in a short time by using existing bubble clouds as reflectors, and it was confirmed that focus scanning is effective in efficiently expanding the region of bubble cloud generation, as shown in a previous study. 29) In the ex vivo experiment shown in Fig. 6, four-point sonication expanded the treated area in both directions of the HIFU propagation axis compared to one-point sonication.…”

“…3 The sonication time for the first focal point (A) was 90 μs to increase the probability of cavitation bubble cloud generation, and the sonication time for the second and subsequent points (B, C, and D) was 10 μs. These sequences are based on our previous studies 29) that investigated efficient sonochemiluminescence in hydrogels using the chemical effect of cavitation bubbles. The ultrasound sequence with scanning the focus toward the transducer was created to utilize the mechanism of "shock scattering", 30) in which a cavitation bubble cloud is formed by reflected waves from individual bubbles.…”