Received 2 April 2009; accepted 10 September 2009. published online 23 November 2009.
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.
aDepartment of Urology, University of Michigan, Ann Arbor, Michigan
bDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
Reprint requests: William W. Roberts, M.D., Department of Urology, University of Michigan Health System, 3879 Taubman Center, SPC 5330, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5330
This research was funded in part by grants from the Wallace H. Coulter Foundation and NIH 1K08DK081656-01.
William W. Roberts is entitled to royalties from and is an equity holder in Histosonics, LLC, a private firm which has licensed intellectual property that is referenced in this manuscript.
ABSTRACT