Histotripsy Homogenization of the Prostate: Thresholds for Cavitation Damage of Periprostatic Structures

Abstract

Background and Purpose: Histotripsy is a noninvasive, pulsed ultrasound technology that produces mechanically homogenized tissue within targeted volumes. Previous work has demonstrated prostatic tissue debulking in a canine model. The aim was to establish safety thresholds by evaluating histologic changes of urinary sphincter, neurovascular bundle (NVB), and rectum after targeted histotripsy treatment of these critical structures. Materials and Methods: Rectum, urinary sphincter, and NVB in five anesthetized canines were targeted for histotripsy treatment (50 total points). Locations received 1k, 10k, or 100k acoustic pulses (4 microsecond, 1 MHz) at a repetition frequency of 500 Hz. Canine subjects were euthanized immediately (2), survived 3 days (1), or 2 weeks (3) after treatment. Prostates, periprostatic tissue, and rectum were harvested and processed for histology. Results: The sphincter was structurally intact with minimal muscle fiber disruption even after 100k pulses (n = 10). Undamaged nerves, arteries, and veins of the NVB were seen despite mechanical homogenization of surrounding loose connective tissue (n = 19). The rectum, however, exhibited dose-dependent damage (n = 20). 1k pulses yielded mild submucosal hemorrhage. 10k pulses resulted in moderate collagen disruption and focal mucosal homogenization. 100k pulses produced damage to the mucosa and muscularis propria with extensive hemorrhage and collagen disruption. One canine treated with 100k pulses needed early euthanasia (day 3) because of complications from a urine leak. Conclusions: Histotripsy histologic tissue effect varied based on targeted structure with substantial structural preservation of NVB and sphincter. Rectal subclinical damage was apparent after 1k pulses and increased in extent and severity with escalating doses. Future work will include assessment of functional outcomes and refinement of these initial safety thresholds.

The potential utility of high-intensity ultrasound to treat osteoarthritis

“…Current treatment of meniscus or cartilage damage includes the intra-articular removal of damaged tissue with mechanical shavers 90,91 , saline jets 92 , and radiofrequency tools 90e92 . Ultrasound has been used to remove tissue by homogenization, debridement and/or thermal ablation 75,93 . Examples of these are debridement of meniscus 93 , corneal phacoemulsification 94 and thermal ablation of tumors in the prostate, breast, bone, brain, liver, and uterus 47 (Table II).…”

“…Histotripsy is a technique where bubbles are collapsed and high speed fluid micro-jets disrupt tissue. In contrary to thermal HIFU approaches, histotripsy is based on introducing shear forces exceeding the fracture strength of the tissue at the site of the cavitation bubble cloud 75 . An advanced HIU surgical tool could image, cut, shape or ablate irregularities within the cartilage tissue using a noninvasive approach while avoiding heating problems within the tissue.…”

Histotripsy of the Prostate Using a Commercial System in a Canine Model

“…[14][15][16][17] Efforts to translate this technology from the university research laboratory to the clinical setting necessitated the formation of a company, HistoSonics, Inc., where subsequent development and refinement resulted in creation of a clinical prototype named VORTX R X ® (Figure 1). The objective of this study was to assess local and systemic effects following prostate histotripsy using this prototype system in a canine model.…”

Histotripsy Effects on the Bladder Trigone: Functional and Histologic Consequences in the Canine Model

“…In an earlier study, the periprostatic neurovascular bundles and urinary sphincter were found to Departments of 1 Urology, be resilient to structural damage even at supratherapeutic histotripsy doses (up to 100k pulses targeted on a single point). 7 The histotripsy threshold for cavitational injury to the rectum was lower such that collagen disruption and hemorrhage were seen when >10,000 histotripsy pulses were applied directly to the rectal wall. 7 In this study, we sought to characterize the tissue effects and biologic response of the bladder trigone and ureteral orifices to direct application of histotripsy therapy.…”

“…7 The histotripsy threshold for cavitational injury to the rectum was lower such that collagen disruption and hemorrhage were seen when >10,000 histotripsy pulses were applied directly to the rectal wall. 7 In this study, we sought to characterize the tissue effects and biologic response of the bladder trigone and ureteral orifices to direct application of histotripsy therapy.…”