Аннотация:Boiling histotripsy (BH) has emerged in recent years as a HIFU-based method of tissue fractionation. BH utilizes millisecond-long bursts of HIFU shock waves that cause boiling in milliseconds, and the subsequent interaction of the incoming shocks with the lboiling bubble yses the surrounding tissue. The acoustic parameter space for BH has been investigated previously. In particular, the inverse dependence between the HIFU frequency and the dimensions of a BH lesion has been shown for 1, 2, and3 MHz frequencies. It has also been observed that the lowest 1 MHz frequency, that yielded the largest lesions, the treatment has not been as consistent as those generated at 2 MHz and 3 MHz. The hypothesized reason for this effect was stronger cavitation in the prefocal region which shielded the shock waves from penetrating to the focus and causing rapid boiling. The goal of this study was to better understand the effect of HIFU frequency for generating BH lesions within the range of 1-2 MHz by observing the ensuing bubble activity in transparent gel phantoms and ex vivo tissue.
A broadband 12-element HIFU transducer operating in the frequency range of 1-2 MHz with f-number equal to one was used in all experiments (Fig. 1a). BH pulsing schemes at five different frequencies (1, 1.2, 1.5, 1.7 and 2 MHz) and equal number of shocks per pulse were delivered to the optically transparent polyacrylamide gel phantoms to visually observe the cavitation and boiling bubble activity. The exposures were then repeated in ex vivo bovine liver tissue, and the bubble activity was characterized by B-mode ultrasound imaging and passive cavitation detection (PCD). The transducer output power was adjusted for each frequency to result in the same in situ focal peak pressure levels.
A cavitation bubble cloud was shown to form prefocally in most exposures in gel phantoms at 1 MHz and 1.2 MHz, but not at 1.5-2 MHz. When the bubble cloud formed, millisecond boiling was not observed for each pulse. In ex vivo experiments, the liquefied lesions did not form in some of the exposures at 1-1.2 MHz. In these exposures, strong broadband emissions were registered by the PCD immediately as the first pulse was delivered, suggesting strong prefocal cavitation, although not sufficient to generate mechanical tissue fragmentation. Conversely, at 1.5-2 MHz the strong broadband emissions started after a few milliseconds of exposure, i.e. after boiling had started. The inverse dependence of the resulting liquefied lesion size on frequency was also confirmed.
The observations reported herein indicate that 1.5-1.7 MHz frequency range may be more suitable to utilize BH mechanism of tissue fractionation. At these frequencies, the peak negative pressure in the prefocal area appears to be below the cavitation threshold in gel and ex vivo tissue samples while shock amplitude is sufficienly high to induce boiling withi each millisecond-long pulse In addition, the lesion size is larger, and the intervening tissue attenuation is lower enabling deeper penetration depth in tissue than those at 2 MHz and higher frequencies. This work was supported by NIH EB7643 and K01 EB 015745.