title: Histotripsy: minimally invasive technology for prostatic tissue ablation in an in vivo canine model.
abstract: OBJECTIVE
  Symptoms of benign prostatic hyperplasia affect men increasingly as they age. Minimally invasive therapies for the treatment of benign prostatic hyperplasia continue to evolve. We describe histotripsy, a noninvasive, nonthermal, focused ultrasound technology for precise tissue ablation, and report the initial results of using histotripsy for prostatic tissue ablation in an in vivo canine model.
  
  
  METHODS
  An annular 18-element, 750-kHz, phased-array ultrasound system delivered high-intensity (22 kW/cm(2)), ultrasound pulses (15 cycles in 20 ms) at pulse repetition frequencies of 100 to 500 Hz to canine prostates. Eight lateral lobe and nine periurethral treatments were performed in 11 anesthetized dogs. Diagnostic ultrasound transducers provided in-line and transrectal imaging. Retrograde urethrography was performed before and after the periurethral treatments. After treatment, the prostates were grossly examined, sectioned, and submitted for histologic examination.
  
  
  RESULTS
  In the lateral lobe treatments, a well-demarcated cavity containing liquefied material was present at the ablation site. Microscopically, the targeted volume was characterized by the presence of histotripsy paste (debris, absent cellular structures). A narrow margin of cellular injury was noted, beyond which no tissue damage was apparent. The periurethral treatments resulted in total urethral ablation or significant urethral wall damage, with visible prostatic urethral defects on retrograde urethrography. Real-time ultrasound imaging demonstrated a dynamic hyperechoic zone at the focus, indicative of cavitation and suggesting effective tissue ablation.
  
  
  CONCLUSIONS
  The results of our study have shown that histotripsy is capable of precise prostatic tissue destruction and results in subcellular fractionation of prostate parenchyma. Histotripsy can also produce prostatic urethral damage and thereby facilitate drainage of finely fractionated material per urethra, producing immediate debulking.
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA. alilake@med.umich.edu
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lake
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Hall
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kieran
authors.forename: J Brian
authors.initials: JB
authors.lastname: Fowlkes
authors.forename: Charles A
authors.initials: CA
authors.lastname: Cain
authors.forename: William W
authors.initials: WW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004867:Equipment Design; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000628:therapy*; D013347:Subcellular Fractions; D014464:Ultrasonic Therapy; D036761:Ultrasound, High-Intensity Focused, Transrectal / Q000295:instrumentation* / Q000379:methods*