Histotripsy Beyond the Intrinsic Cavitation Threshold Using Very Short Ultrasound Pulses: Microtripsy

Histotripsy produces tissue fractionation through dense energetic bubble clouds generated by short, high-pressure, ultrasound pulses. Conventional histotripsy treatments have used longer pulses from 3 to 10 cycles, wherein the lesion-producing bubble cloud generation depends on the pressure-release scattering of very high peak positive shock fronts from previously initiated, sparsely distributed bubbles (the shock-scattering mechanism). In our recent work, the peak negative pressure (P-) for generation of dense bubble clouds directly by a single negative half cycle, the intrinsic threshold, was measured. In this paper, the dense bubble clouds and resulting lesions (in red blood cell phantoms and canine tissues) generated by these supra-intrinsic threshold pulses were studied. A 32-element, PZT-8, 500-kHz therapy transducer was used to generate very short (<2 cycles) histotripsy pulses at a pulse repetition frequency (PRF) of 1 Hz and P- from 24.5 to 80.7 MPa. The results showed that the spatial extent of the histotripsy-induced lesions increased as the applied P- increased, and the sizes of these lesions corresponded well to the estimates of the focal regions above the intrinsic cavitation threshold, at least in the lower pressure regime (P- =26 to 35 MPa). The average sizes for the smallest reproducible lesions were approximately 0.9 x 1.7 mm (lateral x axial), significantly smaller than the -6-dB beamwidth of the transducer (1.8 x 4.0 mm). These results suggest that, using the intrinsic threshold mechanism, well-confined and microscopic lesions can be precisely generated and their spatial extent can be estimated based on the fraction of the focal region exceeding the intrinsic cavitation threshold. Because the supra-threshold portion of the negative half cycle can be precisely controlled, lesions considerably less than a wavelength are easily produced, hence the term microtripsy.