The histotripsy spectrum: differences and similarities in techniques and instrumentation

Abstract

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F-number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications.

Keywords: High intensity focused ultrasound; boiling histotripsy; cavitation; histotripsy; nonlinear propagation.

Figure 1.

Histotripsy techniques and associated representative acoustic parameters. The year refers to the time when each technique was first reported in literature, but not yet necessarily termed the way it is currently known. HIFU transducer F-number is the ratio of its radius of curvature (focal length) to the aperture diameter. The first two types are typically used at frequencies less than 1 MHz, and last two at frequencies higher than 1 MHz.

Figure 2.

Comparison of typical focal pressure waveforms (top row), free-field axial beam profiles (middle row), and resulting bubble distributions for intrinsic threshold histotripsy (left column), shock scattering histotripsy (middle column), and boiling histotripsy (right column). For intrinsic threshold histotripsy, a short pulse is generated with a single dominant tensile pressure cycle exceeding the intrinsic threshold. Both shock scattering histotripsy and boiling histotripsy utilize focal pressure waveforms containing high amplitude shocks at the focus, and a bubble cloud forms due to interaction of the shocks with an initially formed (incidental) bubble. In shock scattering histotripsy, the initial bubble forms in response to one or more tensile phases of the excitation pressure, while shock-induced heating causes the primary vapor bubble to form in boiling histotripsy. Note that the bubbles have not been drawn to scale.

Figure 3.

Examples of transducers used for intrinsic threshold histotripsy (a, b), shock-scattering histotripsy (c, d), and boiling histotripsy (e, f, g). Subfigures (a) and (b) are modified from [75] and [73], respectively, and are licensed under a Creative Commons Attribution License (CC BY 4.0).