Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney

Tatiana D Khokhlova,Frank Starr,Yak-Nam Wang,Vera A Khokhlova,Wayne Kreider,Valeriy P Chernikov,Julianna C Simon,Adam D Maxwell,Sergey V Buravkov,Michael R Bailey,George R Schade

doi:10.1038/s41598-019-56658-7

Abstract

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5–30 pulses of 1–10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9–3.8 kW, sonication foci spaced 1–1.5 mm apart in a rectangular grid with 5–15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.

Highlights

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks
The clinical HIFU sonication regimes implemented for most clinical applications, including hepatocellular carcinoma (HCC) and Renal cell carcinoma (RCC) therapy, produce thermal ablation and are performed under MR thermometry or ultrasound imaging guidance[14,15,16]
Targeting and treatment monitoring were performed with B-mode ultrasound imaging, with the imaging probe located in the central opening of the HIFU transducer

Summary

Introduction

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. Respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver. The clinical HIFU sonication regimes implemented for most clinical applications, including HCC and RCC therapy, produce thermal ablation and are performed under MR thermometry or ultrasound imaging guidance[14,15,16]. Recent developments in HIFU technology have enabled several alternative approaches, collectively known as histotripsy, that mechanically fractionate or liquefy targeted tissue[17,18] In these approaches, high amplitude ultrasound pulses are delivered at low duty cycle to produce and activate gas and vapor bubbles at the focus leading to disintegration of tissue into subcellular debris. The non-thermal nature of this approach removes limitations on treatment precision related to both heat sinking effects and collateral thermal damage associated with heat diffusion

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