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Aim: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer., Methods: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy., Results: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum., Conclusion: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.