Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue

Vera A Khokhlova; Pavel B Rosnitskiy; Sergey A Tsysar; Sergey V Buravkov; Ekaterina M Ponomarchuk; Oleg A Sapozhnikov; Maria M Karzova; Tatiana D Khokhlova; Adam D Maxwell; Yak-Nam Wang; Alexey V Kadrev; Andrey L Chernyaev; Valery P Chernikov; Dmitriy A Okhobotov; Armais A Kamalov; George R Schade

doi:10.1016/j.ultrasmedbio.2022.07.014

Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue

Ultrasound Med Biol. 2023 Jan;49(1):62-71. doi: 10.1016/j.ultrasmedbio.2022.07.014. Epub 2022 Oct 4.

Authors

Vera A Khokhlova¹, Pavel B Rosnitskiy², Sergey A Tsysar², Sergey V Buravkov³, Ekaterina M Ponomarchuk², Oleg A Sapozhnikov⁴, Maria M Karzova², Tatiana D Khokhlova⁵, Adam D Maxwell⁶, Yak-Nam Wang⁷, Alexey V Kadrev⁸, Andrey L Chernyaev⁹, Valery P Chernikov¹⁰, Dmitriy A Okhobotov¹¹, Armais A Kamalov¹¹, George R Schade⁶

Affiliations

¹ Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA; Physics Faculty, Lomonosov Moscow State University, Moscow, Russia. Electronic address: verak2@uw.edu.
² Physics Faculty, Lomonosov Moscow State University, Moscow, Russia.
³ Laboratory of Cell Image Analysis, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia; Research Institute of Human Morphology, Moscow, Russia.
⁴ Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA; Physics Faculty, Lomonosov Moscow State University, Moscow, Russia.
⁵ Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
⁶ Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA.
⁷ Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.
⁸ Medical Research and Educational Center, Department of Urology and Andrology, Lomonosov Moscow State University, Moscow, Russia; Diagnostic Ultrasound Division, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
⁹ Research Institute of Human Morphology, Moscow, Russia; Pulmonology Scientific Research Institute, Moscow, Russia.
¹⁰ Research Institute of Human Morphology, Moscow, Russia.
¹¹ Medical Research and Educational Center, Department of Urology and Andrology, Lomonosov Moscow State University, Moscow, Russia.

Abstract

Boiling histotripsy (BH) is a focused ultrasound technology that uses millisecond-long pulses with shock fronts to induce mechanical tissue ablation. The pulsing scheme and mechanisms of BH differ from those of cavitation cloud histotripsy, which was previously developed for benign prostatic hyperplasia. The goal of the work described here was to evaluate the feasibility of using BH to ablate fresh ex vivo human prostate tissue as a proof of principle for developing BH for prostate applications. Fresh human prostate samples (N = 24) were obtained via rapid autopsy (<24 h after death, institutional review board exempt). Samples were analyzed using shear wave elastography to ensure that mechanical properties of autopsy tissue were clinically representative. Samples were exposed to BH using 10- or 1-ms pulses with 1% duty cycle under real-time B-mode and Doppler imaging. Volumetric lesions were created by sonicating 1-4 rectangular planes spaced 1 mm apart, containing a grid of foci spaced 1-2 mm apart. Tissue then was evaluated grossly and histologically, and the lesion content was analyzed using transmission electron microscopy and scanning electron microscopy. Observed shear wave elastography characterization of ex vivo prostate tissue (37.9 ± 22.2 kPa) was within the typical range observed clinically. During BH, hyperechoic regions were visualized at the focus on B-mode, and BH-induced bubbles were also detected using power Doppler. As treatment progressed, hypoechoic regions of tissue appeared, suggesting successful tissue fractionation. BH treatment was twofold faster using shorter pulses (1 ms vs. 10 ms). Histological analysis revealed lesions containing completely homogenized cell debris, consistent with histotripsy-induced mechanical ablation. It was therefore determined that BH is feasible in fresh ex vivo human prostate tissue producing desired mechanical ablation. The study supports further work aimed at translating BH technology as a clinical option for prostate ablation.

Keywords: Boiling histotripsy; High-intensity focused ultrasound; Prostate.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

High-Intensity Focused Ultrasound Ablation* / methods
Humans
Male
Prostate / diagnostic imaging
Prostate / surgery

Abstract

Publication types

MeSH terms

Grants and funding