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”).

Cavitation Control and Applications

“…The phase transition occurs when the surrounding pressure decreases below the saturated vapor pressure of the nanodroplets. Hence, this change in local pressure drives the phase transformation (Lin and Pitt 2013). But, changes in temperature can also influence the droplet's degree of superheating, which is related to the threshold of the local pressure for phase transition.…”

Cavitation-Enhanced Thermal Effects and Applications

“…This technique has been dubbed "histotripsy" as an analog to lithotripsy (Xu et al 2004(Xu et al , 2005(Xu et al , 2010. Lin et al (2014) used very short (<2 cycles) of histotripsy pulses to generate dense bubble clouds and a precise, subwavelength lesion, and called this procedure "microtripsy." Shock wave heating and millisecond boiling in HIFU fields, known as "boiling histotripsy," use millisecond pulses with lower pulse repetition frequency and acoustic pressures than used in cavitation cloud histotripsy to expand a millimeter-sized boiling bubble at the transducer focus explosively, resulting in mechanical fractionation or emulsification of tissue (Khokhlova et al 2011;Wang et al 2013;Simon et al 2012;Maxwell et al 2012).…”

Nonlinear generation of harmonic content within High Intensity Ultrasound signals using granular chains

“…In ultrasound therapy, short duration high-pressure ultrasound pulses create a compact, dense high energy region and reduce the possibility of hot-spots by reducing undesirable constructive interference. In histotripsy, short duration negative monopolar pulses can inhibit shock scattering [4], [5]. In High Intensity Focused Ultrasound (HIFU), a precise control on the focal region is necessary to minimise the potential collateral damage in the surrounding healthy tissue.…”