Histotripsy beyond the “intrinsic” cavitation threshold using very short ultrasound pulses: “Microtripsy”

Abstract

Conventional histotripsy uses pulses with ≥3 cycles wherein the bubble cloud formation relies on the pressure-release scattering of the positive shock fronts from sparsely distributed cavitation bubbles. In a recent work, the peak negative pressure (P(-)) threshold for the generation of dense bubble clouds directly by a negative half cycle were measured, and this threshold has been called the “intrinsic threshold.” In this work, characteristics of lesions generated with this intrinsic threshold mechanism were investigated using RBC phantoms and excised canine tissues. A 32-element, PZT-8, 500 kHz therapy transducer was used to generate short (<2 cycles) histotripsy pulses at PRF = 1Hz and P(-) = 24.5–80.7 MPa. The results showed that the spatial extent of the histotripsy-induced lesions increased as the applied P(-) increased, and the lesion sizes corresponded well to the estimates of the focal regions above the intrinsic threshold. The sizes for the smallest reproducible lesions averaged 0.9 × 1.7mm (lateral × axial), significantly smaller than −6 dB beamwidth of the transducer (1.8 × 4.0 mm). These results suggest that predictable, well-confined and microscopic lesions can be precisely generated using the intrinsic threshold mechanism. Since the supra-threshold portion of the negative half cycle can be precisely controlled, lesions considerably less than a wavelength are easily produced (“microtripsy”).