Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling

Abstract

In high intensity focused ultrasound (HIFU) applications, tissue may be thermally necrosed by heating, emulsified by cavitation, or, as was recently discovered, emulsified using repetitive millisecond boiling caused by shock wave heating. Here, this last approach was further investigated. Experiments were performed in transparent gels and ex vivo bovine heart tissue using 1, 2, and 3 MHz focused transducers and different pulsing schemes in which the pressure, duty factor, and pulse duration were varied. A previously developed derating procedure to determine in situ shock amplitudes and the time-to-boil was refined. Treatments were monitored using B-mode ultrasound. Both inertial cavitation and boiling were observed during exposures, but emulsification occurred only when shocks and boiling were present. Emulsified lesions without thermal denaturation were produced with shock amplitudes sufficient to induce boiling in less than 20 ms, duty factors of less than 0.02, and pulse lengths shorter than 30 ms. Higher duty factors or longer pulses produced varying degrees of thermal denaturation combined with mechanical emulsification. Larger lesions were obtained using lower ultrasound frequencies. The results show that shock wave heating and millisecond boiling is an effective and reliable way to emulsify tissue while monitoring the treatment with ultrasound.

Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model

“…This procedure measured the time to boil, t b , which is an essential parameter for pulsing protocol design. According to our previous findings in ex vivo tissue, the ratio between the time to reach boiling, t b , and the pulse duration, τ, determines the treatment outcome, along with the duty factor (ratio of the pulse duration and the pulse repetition period) (11,13). In accordance with theoretical estimations, t b The idea behind boiling-histotripsy exposures is to make use of highly nonlinear ultrasound waves that form at the HIFU focus and contain shock fronts.…”

“…ultimately its complete fractionation (11). When the HIFU pulse parameters are controlled so that the pulse length is not much longer than the time to boil, t b , and the pulse repetition frequency is low enough to avoid heat accumulation, thermal injury to tissue is negligible.…”

“…Moreover, the requirements on the size, focusing gain (f-number 1), and frequency of the HIFU source are less restrictive, which is an advantage when only a limited acoustic window is available. It has also been shown that both boiling histotripsy and cavitation cloud histotripsy procedures can be targeted and monitored with B-mode ultrasound, because both boiling bubbles and cavitation bubble clouds are highly reflective (11).…”

“…At its extreme, bubble activity can cause complete homogenization (liquefaction) of tissue. In particular, controllable, localized ex vivo tissue lysis has been achieved through the generation of a millimeter-size boiling bubble and its interaction with the HIFU field (11). The underlying physical mechanism can be described as follows: When high acoustic pressure waves propagate through water or tissue to the focus, nonlinear effects lead to the transformation of the initial sine wave generated by the transducer into a sawtooth-shaped shock wave in the focal region.…”

“…The second goal was to validate in vivo the approach to the choice of the treatment protocol parameters (e.g., pulse duration, duty factor, focal pressure levels), which was proposed in our prior ex vivo studies (11). The latter aim required the side-by-side comparison of the outcomes of the different boiling histotripsy protocols in vivo and ex vivo in terms of the lesion size, shape, and content.…”