Phase-shift nano-emulsions induced cavitation and ablation during high intensity focused ultrasound exposure

Abstract

Phase-shift Nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The aim of this work was to provide spatial and temporal information on PSNE induced cavitation and ablation effects during pulsed high intensity focused ultrasound (HIFU) exposure. The PSNEs were composed of perfluorohaxane (PFH) and bovine serum albumin (BSA), and then uniformly distributed in a transparent polyacrylamide phantom. The Sonoluminescence (SL) method was employed to visualize the cavitation distribution and formation process of PSNEs induced cavitation. For the phantom which was used for ablation observation, heat sensitive BSA was added. When the temperature generated by ultrasound exposure was high enough to denature BSA, the transparent phantom would turn out white lesions. The shape of the lesion and the formation process were compared with those of cavitation. Each of the pulse contained 12 cycles for a duration of 10 µs. And the duty cycle changed from 1:10 to 1:40. The total "on" time of HIFU was 2s. PSNE can evidently accelerate cavitation emitting bright SL in pre-focal region. The cavitation was generated layer by layer towards the transducer. The formed bubble wall can block acoustic waves transmitting to the distal end. And the lesion appeared to be separated into two parts. One in pre-focal region stemmed from one point and grew quickly toward the transducer. The other in focal region was formed by merging some small white dots, and grew much slower. The influence of duty cycle has also been examined. The lower duty cycle with longer pulse-off time would generate more intense cavitation, however, smaller lesion. Bubble cloud gradually developed within phantom would greatly influence the cavitation and ablation process. One hand, the evaporated bubbles could enhance both the cavitation and thermal effects of HIFU. The other hand, outside layer bubbles would block the acoustic wave transmission, inducing distinctive cavitation and ablation formation process. The spatial distribution of cavitation and lesion organized into special structures under different acoustic parameters.