title: Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customised MRI-based moulds.
abstract: OBJECTIVE
  To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
  
  
  METHODS
  Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland). MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy. After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability. Statistical analyses (Pearson's correlation, Student's t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
  
  
  RESULTS
  MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions. Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r(2) 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r(2) 0.89, P < 0.001, and r(2) 0.91, P = 0.003, respectively). Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r(2) 0.77, P < 0.01). There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student's t-test).
  
  
  CONCLUSIONS
  MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model. Ablation volumes were reliably predicted by intra- and post-procedural imaging. Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.
authors.affiliation: Philips Healthcare, Cleveland, OH; Department of Physics, University of Helsinki, Helsinki, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Partanen
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Yerram
authors.forename: Hari
authors.initials: H
authors.lastname: Trivedi
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Juha
authors.initials: J
authors.lastname: Oila
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hoang
authors.forename: Dmitry
authors.initials: D
authors.lastname: Volkin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nix
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.forename: Compton J
authors.initials: CJ
authors.lastname: Benjamin
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: Gösta J
authors.initials: GJ
authors.lastname: Ehnholm
authors.forename: Aradhana M
authors.initials: AM
authors.lastname: Venkatesan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Pinto
mesh_terms: D000818:Animals; D004285:Dogs; D008279:Magnetic Resonance Imaging; D008297:Male; D008953:Models, Anatomic; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D014464:Ultrasonic Therapy / Q000379:methods*; D014521:Urethra
keywords: image-guided therapy; magnetic resonance imaging; minimally invasive therapy; therapeutic ultrasound; thermal ablation; thermotherapy