Effects off-number on the histotripsy intrinsic threshold and cavitation bubble cloud behavior

Abstract

Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Although previous work has provided significant insight into the process of intrinsic threshold histotripsy, the majority of these studies have used highly focused (i.e. f-number<0.6) transducers. In this study, we investigate the effects of f-number on the histotripsy intrinsic threshold and cavitation bubble cloud behavior using a 500 kHz array transducer, with the effective f-number of the transducer varied from 0.51 to 0.89. The intrinsic threshold did not significantly change with f-number, with the threshold remaining ~27–30 MPa for all conditions. The predictability of intrinsic threshold histotripsy was further demonstrated by experiments comparing the predicted and experimentally measured bubble cloud dimensions, with results showing close agreement for all f-numbers. Finally, the effects of f-number on “bubble density” and tissue fractionation efficiency were investigated, with results supporting the hypothesis that the density of the bubbles within the bubble cloud significantly decreases at higher f-numbers, resulting in decreased fractionation efficiency. Overall, this study provides significant insight into the effects of f-number on intrinsic threshold histotripsy that will help to guide the development of intrinsic threshold histotripsy for specific clinical applications.

Effect of Frequency and Focal Spacing on Transcranial Histotripsy Clot Liquefaction, Using Electronic Focal Steering

“…An understanding of the reasons for this can be approached by considering the pressure steering profiles and the geometric focal pressure for the 250 and 500 kHz array. As the lesion size correlates well with the dimensions of the focus above the intrinsic threshold (Vlaisavljevich et al 2017) and the 1D beam profiles (Fig. 2) show a much larger focal region at 250 kHz, the focal spacing was made proportional to the frequency of the array.…”

For Whom the Bubble Grows: Physical Principles of Bubble Nucleation and Dynamics in Histotripsy Ultrasound Therapy

“…The total focal volume, and therefore the total number of insonated nuclei, will be dictated by the frequency and transducer geometry. No significant changes have been observed in the intrinsic cavitation threshold for 500-kHz transducers with f-numbers between 0.5 and 0.9 (Vlaisavljevich et al 2017a).…”

“…That is, bubbles can be nucleated before the onset of strong non-linearities for intrinsic threshold pulses. The bubble cloud density within the focal regions is also significantly increased for low f-number sources (Vlaisavljevich et al 2017a).…”

“…The most efficient means of generating large tension within the focus are sources with high focal gain or low f-number, defined for a spherically focused source as the ratio of focal distance to aperture diameter. As non-linear effects accumulate with propagation distance (Hamilton and Blackstock 1998), the pressure within the focus of low f-number sources (»0.5À0.7) consequently remains in a nearlinear regime when generating cavitation (Vlaisavljevich et al 2017a). As the f-number of the source increases, a non-linear wave will form, as depicted in Figure 3.…”

“…Single bubbles appear in the focus when the tension is near the intrinsic threshold (Maxwell et al 2013). As the pressure amplitude is increased, the cavitating volume is increased in proportion to the volume of the focal zone exceeding the intrinsic threshold (Vlaisavljevich et al 2017a). Once expansion ensues, the bubble dynamics match those of a pure Blake cavity during the acoustic excitation.…”