To develop the technique of histotripsy ultrasound therapy as a noninvasive treatment for benign prostatic hyperplasia and to examine the histotripsy dose-tissue response effect over time to provide an insight for treatment optimization. We have previously demonstrated the feasibility of prostate histotripsy fractionation in a canine model.

Various doses of histotripsy were applied transabdominally to the prostates of 20 canine subjects. Treated prostates were then harvested at interval time points from 0 to 28 days and assessed for histologic treatment response.

The lowest dose applied was found to produce only scattered cellular disruption and necrosis, whereas higher doses produced more significant regions of tissue effect that resulted in sufficient fractionation of tissue so the material could be voided with urination. Urethral tissue was more resistant to the lower histotripsy doses than was parenchymal tissue. Treatment of the urethra at the lowest doses appeared to heal, with minimal long-term sequelae.

Histotripsy was effective at fractionating parenchymal and urethral tissue in the prostate, in the presence of a sufficient dose. Further development of this technique could lead to a noninvasive method for debulking the prostate to relieve symptoms associated with benign prostatic hyperplasia.