Prostate Histotripsy in an Anticoagulated Model

Objectives

To further explore the phenomenon of minimal bleeding after histotripsy by performing extensive prostate histotripsy treatments in anticoagulated canines. Histotripsy is a noninvasive ultrasound technology which induces microbubble formation (cavitation) within tissues producing mechanical tissue fractionation. During initial in vivo feasibility canine studies of prostate ablation, minimal hematuria was observed.

Methods

Histotripsy was performed on 9 canine subjects pretreated with 6 mg of oral warfarin for 3-5 days using an extracorporeal 750 kHz therapeutic ultrasound transducer delivering acoustic pulses to the prostatic urethra and periurethral parenchyma. After 7-28 days, the subjects were euthanized, transrectal prostate ultrasound was performed, and the prostate was harvested. Serum hemoglobin and International Normalization Ratio were measured immediately before histotripsy treatment and at euthanasia.

Results

Mean treatment International Normalization Ratio was 4.6 (median, 2.4; range, 1.2-11.3). There was no clinically significant change in hemoglobin concentration at euthanasia compared with baseline. At harvest, histologic sections of the prostate revealed a large cavity corresponding to the planned treatment volume incorporating the prostatic urethra and parenchyma in all subjects. Urine was clear within 2 days of treatment, and no blood clots were seen.

Conclusions

Despite therapeutic and supratherapeutic anticoagulation, histotripsy resulted in minimal bleeding despite significant fractionation and tissue debulking of the prostate. These results have prompted further studies to understand the mechanism of nonthermal hemostasis underlying histotripsy.