Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate

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

Figures

Figure 1

Trans-urethral ultrasound therapy probe. Rigid, water-cooled trans-urethral ultrasound applicator with 5 mm (15 French) diameter and eight transducer elements (4 mm × 5 mm/element).

Figure 2

Magnetic resonance imaging-compatible ultrasound therapy device. Set-up of the trans-urethral ultrasound applicator on the MRI patient table with control cables, and motor unit to control the rotation of the ultrasound transducer. MRI: Magnetic resonance imaging.

Figure 3

Equipment integration for magnetic resonance imaging-guided ultrasound therapy. Frontal oblique view of the 3T Philips MRI scanner with an 8-channel cardiac MR coil on the anterior part of the scanner table and ultrasound transducer on the posterior part of scanner table. MRI: Magnetic resonance imaging.

Figure 4

Canine positioning for magnetic resonance imaging-guided ultrasound therapy. Positioning of a canine in supine orientation on the patient table and preparation for the placement of the transurethral ultrasound transducer in the canine prostate.

Figure 5

The CaverMap Surgical Aid nerve stimulator control unit. Device control unit with connectors for the stimulation needle, display of the applied current in mA, and light-emitting diode display (blue and red) to visualize tumescence response on an ordinal scale.

Figure 6

Surgical preparation of the canine prostate for nerve stimulation of the cavernosal nerves.

Figure 7

Placement of the CaverMap Surgical Aid nerve stimulator (A and B). Intrasurgical placement of the stimulation needle of the CaverMap Surgical Aid nerve stimulator close to the cavernosal nerves of the canine prostate.

Figure 8

The CaverMap Surgical Aid nerve stimulator display. Control unit and display of the CaverMap Surgical Aid nerve stimulator to measure tumescence response on an ordinal scale intraoperatively. Below the digital display are the connectors for the probe handle, the tumescence sensor, and the lead for connecting the tumescence sensor to the control unit. The electric current for stimulation is emitted by the probe tip.

Figure 9

Explanted canine prostate and bladder after prostatectomy.

Figure 10

Histology of treated canine prostate. Series of histological slides of a canine prostate after H and E staining show ultrasound ablation zones and hemorrhage.

Figure 11

Example images of planning, treatment, and histological outcome. A: Coronal MR image of the intra-urethral catheter placement in the canine prostate for treatment planning with the canine in supine position: The ultrasound applicator is forwarded in the penile urethra to the prostate; B: Color-coded axial temperature map overlaid on the corresponding anatomical MR image demonstrates the typical temperature distribution post ultrasound treatment. Proton Resonance Frequency Shift measurements with a FFE-EPI imaging sequence were used for temperature monitoring and control; C: Sagittal temperature map during ultrasound treatment; D: Histological slide of the canine prostate in haematoxylin and eosin staining to evaluate ultrasound treatment effects. MR: Magnetic resonance; FFE: Fast-field echo.

Figure 12

Representative images of magnetic resonance imaging-guidance. A: T2-weighted image for positioning and treatment planning in axial and sagittal orientation (B); C: MR temperature map during ultrasound treatment in axial and sagittal orientation (D); E: MR dose map during ultrasound treatment in axial and sagittal orientation (F); G: Contrast enhanced T1-weighted image after ultrasound treatment. MR: Magnetic resonance.