Development and translation of histotripsy: current status and future directions

Abstract

Purpose of review: The aim of this article is to outline the initial development of histotripsy, a noninvasive image-guided focused ultrasound technology that mechanically homogenizes targeted tissues and to describe the results of preclinical translational research directed toward urologic applications.

Recent findings: Histotripsy tissue ablation is based on initiation and control of acoustic cavitation at a target point within the body. This unique mechanical mechanism of action is distinct when compared with conventional thermal ablative modalities. Features of histotripsy (nonthermal, noninvasive, high precision, real-time monitoring/feedback, and tissue liquefaction) have prompted assessment of this technology as a potential ablative therapy for a number of organs and disease processes.

Summary: Ongoing research efforts to apply histotripsy to preclinical models of benign prostatic hyperplasia, prostate cancer, renal masses, and renal calculi have resulted in enhanced understanding of cavitation bioeffects, refinement of treatment systems, strategies to enhance treatment efficiency, and initiation of a pilot human clinical trial to assess the safety of histotripsy for benign prostatic hyperplasia therapy.

Figure 1

The histotripsy bubble cloud is seen (circle) within a canine prostate (lateral margins marked by arrows on this transverse transrectal ultrasound image. Histotripsy is applied from an extracorporeal therapy transducer located in a suprapubic location (beyond the top of this image.

Figure 2

A transverse transrectal ultrasound image (left) of the red blood cell prostate phantom imaged within a human pelvic phantom after application of histotripsy in a “plus” pattern. The same prostate red blood cell phantom after removal and transverse sectioning reveals lysis of the red blood cells (lighter region) corresponding to the same pattern of cellular homogenization seen with ultrasound overlayed with a 1mm grid.

Figure 3

Experimental histotripsy apparatus in use during canine prostate treatment. A power supply and driving electronics (left) supply power to the histotripsy transducer which is suspended over the suprapubic region of this canine subject in a bath of degassed water. The histotripsy transducer is positioned to locate the focal volume within the prostate. A transrectal ultrasound probe is inserted in the rectum to provide imaging of the prostate and bubble cloud during treatment.

Figure 4

Hematoxylin and eosin stained slide of a prostate harvested four weeks after histotripsy treatment. The cuboidal histotripsy treatment volume is appreciated here as the roughly rectangular empty cavity encompassing both glandular and prostatic urethral tissue.