Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Dec 28, 2015; 7(12): 521-530
Published online Dec 28, 2015. doi: 10.4329/wjr.v7.i12.521
Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate
Steffen Sammet, Ari Partanen, Ambereen Yousuf, Christina L Sammet, Emily V Ward, Craig Wardrip, Marek Niekrasz, Tatjana Antic, Aria Razmaria, Keyvan Farahani, Shunmugavelu Sokka, Gregory Karczmar, Aytekin Oto
Steffen Sammet, Ambereen Yousuf, Emily V Ward, Gregory Karczmar, Aytekin Oto, Department of Radiology, University of Chicago, Chicago, IL 60615, United States
Steffen Sammet, Gregory Karczmar, Committee on Medical Physics, University of Chicago, Chicago, IL 60615, United States
Ari Partanen, Shunmugavelu Sokka, Philips, Andover, MA 01810, United States
Christina L Sammet, Department of Medical Imaging, Lurie Children’s Hospital, Chicago, IL 60611, United States
Craig Wardrip, Marek Niekrasz, Aria Razmaria, Department of Surgery, University of Chicago, Chicago, IL 60615, United States
Tatjana Antic, Department of Pathology, University of Chicago, Chicago, IL 60615, United States
Keyvan Farahani, National Cancer Institute, Bethesda, MD 60615, United States
Author contributions: Sammet S, Partanen A, Yousuf A, Farahani K, Sokka S, Karczmar G and Oto A designed the research; Sammet S, Partanen A, Karczmar G and Oto A developed the MRI protocols; Sammet S, Partanen A and Oto A performed the MRI and therapeutic ultrasound experiments; Antic T performed the histological analysis and the histological/radiological comparison; Oto A performed the radiological image analysis and the histological/radiological comparison; Sammet S, Wardrip C, Niekrasz M and Razmaria A monitored the animals during therapeutic ultrasound treatment and performed surgeries; Sammet S, Partanen A, Yousuf A, Ward EV, Sammet CL, and Oto A wrote the paper.
Supported by The National Cancer Institute Education and Career Development program R25 Cancer Nanotechnology in Imaging and Radiotherapy (5R25CA132822-04) in part; the Cancer Research Foundation; the University of Chicago Comprehensive Cancer Center; and Philips Healthcare.
Institutional review board statement: The study was reviewed and approved by the University of Chicago Institutional Animal Care and Use Committee.
Clinical trial registration statement: This study is not a registered clinical trial.
Informed consent statement: This study did not involve human subjects and therefore did not require informed consent.
Conflict-of-interest statement: Steffen Sammet, MD, PhD has received research funding from Philips Healthcare and fees as a consultant for Guerbet SA. Ari Partanen, PhD is an employee of Philips Healthcare. Shunmugavelu Sokka, PhD is an employee of Philips Healthcare. Aytekin Oto, MD has received research funding from Philips Healthcare and fees as a consultant for Guerbet SA.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Steffen Sammet, MD, PhD, DABR, FAMP, Associate Professor and Director of Clinical MR Physics, Department of Radiology, University of Chicago, 5841 South Maryland Avenue, MC2026, Chicago, IL 60615, United States. ssammet@uchicago.edu
Telephone: +1-773-7023162 Fax: +1-773-7021161
Received: February 7, 2015
Peer-review started: February 8, 2015
First decision: May 19, 2015
Revised: October 19, 2015
Accepted: November 24, 2015
Article in press: November 25, 2015
Published online: December 28, 2015
Processing time: 324 Days and 0.7 Hours
Abstract

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.

Keywords: Ultrasound therapy; Thermal tissue ablation; Prostate; Magnetic resonance imaging guided therapy; Intra-operative; Histology; Validation

Core tip: Therapeutic ultrasound is a promising treatment modality for minimally invasive thermal ablation of tissue. This study assessed a novel trans-urethral ultrasound therapy device with magnetic resonance imaging (MRI) guidance to ablate canine prostate tissue in vivo. Real-time temperature monitoring and thermotherapy feedback control was performed in a clinical 3T whole-body MR scanner. Post-treatment evaluation of cavernous nerve functionality was performed with a nerve stimulator. Treatment accuracy was assessed by correlation of treatment planning, thermal dose maps, and histo-pathological results. Regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in adjacent anatomical structures. These results indicate that MRI-guided transurethral ultrasound therapy can accurately ablate prostatic regions with minimal damage to surrounding tissue.