MR imaging-controlled transurethral ultrasound therapy for conformal treatment of prostate tissue: initial feasibility in humans.

PURPOSE: To evaluate the feasibility and safety of magnetic resonance (MR) imaging-controlled transurethral ultrasound therapy for prostate cancer in humans. MATERIALS AND METHODS: This pilot study was approved by the institutional review board and was performed in eight men (mean age, 60 years; range, 49-70 years) with localized prostate cancer (Gleason score≤7, prostate-specific antigen level #15 µg/L) immediately before radical prostatectomy. All patients provided written informed consent. This phase 0 feasibility and safety study is the first evaluation in humans. Transurethral ultrasound therapy was performed with the patient under spinal anesthesia by using a clinical 1.5-T MR unit. Patients then underwent radical prostatectomy, and the resected gland was sliced in the plane of treatment to compare the MR imaging measurements with the pattern of thermal damage. The overall procedure time and coagulation rate were measured. In addition, the spatial targeting accuracy was evaluated, as was the thermal history along the thermal damage boundaries in the gland. RESULTS: The average procedure time was 3 hours, with 2 or fewer hours spent in the MR unit. The treatment was well tolerated by all patients, and a temperature uncertainty of less than 2°C was observed in the treatments. The mean temperature and thermal dose measured along the boundary of thermal coagulation were 52.3°C±2.1 and 3457 (cumulative equivalent minutes at 43°C)±5580, respectively. The mean treatment rate was 0.5 mL/min, and a spatial targeting accuracy of -1.0 mm±2.6 was achieved. CONCLUSION: MR imaging-controlled transurethral ultrasound therapy is feasible, safe, and well tolerated. This technology could be an attractive approach for whole-gland or focal therapy.

Coagulation of human prostate volumes with MRI-controlled transurethral ultrasound therapy: results in gel phantoms.

PURPOSE: The feasibility and safety of magnetic resonance imaging (MRI)-controlled transurethral ultrasound therapy were demonstrated recently in a preliminary human study in which a small subvolume of prostate tissue was treated prior to radical prostatectomy. Translation of this technology to full clinical use, however, requires the capability to generate thermal coagulation in a volume up to that of the prostate gland itself. The aim of this study was to investigate the parameters required to treat a full 3D human prostate accurately with a multi-element transurethral applicator and multiplanar MR temperature control. METHODS: The approach was a combination of simulations (to select appropriate parameters) followed by experimental confirmation in tissue-mimicking phantoms. A ten-channel, MRI-compatible transurethral ultrasound therapy system was evaluated using six human prostate models (average volume: 36 cm(3)) obtained from the preliminary human feasibility study. Real-time multiplanar MR thermometry at 3 T was used to control the spatial heating pattern in up to nine planes simultaneously. Treatment strategies incorporated both single (4.6 or 8.1 MHz) and dual (4.6 and 14.4 MHz) frequencies, as well as maximum acoustic surface powers of 10 or 20 W cm(-2). RESULTS: Treatments at 4.6 MHz were capable of coagulating a volume equivalent to 97% of the prostate. Increasing power from 10 to 20 W cm(-2) reduced treatment times by approximately 50% with full treatments taking 26 ± 3 min at a coagulation rate of 1.8 ± 0.4 cm(3) min(-1). A dual-frequency 4.6∕14.4 MHz treatment strategy was shown to be the most effective configuration for achieving full human prostate treatment while maintaining good treatment accuracy for small treatment radii. The dual-frequency approach reduced overtreatment close to the prostate base and apex, confirming the simulations. CONCLUSIONS: This study reinforces the capability of MRI-controlled transurethral ultrasound therapy to treat full prostate volumes in a short treatment time with good spatial targeting accuracy and provides key parameters necessary for the next clinical trial.

3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0.1 ± 0.6 °C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool.