Clinical validation of real-time tissue change monitoring during prostate tissue ablation with high intensity focused ultrasound.

BACKGROUND: The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. METHODS: Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients' data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. RESULTS: In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C. CONCLUSIONS: The TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Calibration of a novel, laparoscopic, 12-mm, ultrasound, image-guided, high-intensity focused ultrasound probe for ablation of renal neoplasms.

OBJECTIVE: To calibrate a 12-mm high-intensity focused ultrasound (HIFU) probe to produce histologically verifiable complete tissue necrosis through thermal energy delivery while maintaining safety in ablation of porcine renal tissue. METHODS: The study was approved by the animal research committee at our institution. A HIFU probe on a fixed arm was introduced, and ablation was subsequently carried out robotically (under computer control) at 2 planned locations within each kidney at varying energy levels. After 4 days of survival, kidneys were retrieved and pathologic analysis of the lesions was carried out for necrotic volume. Planned volume was compared with pathologic necrotic volume. RESULTS: A series of optimizations were carried out as the experiment progressed. Near optimal ablation zone dimensions with complete cell death were achieved when the energy density was between 400 and 460 calories/cm(3). Pathologic analysis demonstrated the average ratio of necrotic zone volume to planned zone volume was 1.0 (standard deviation, 0.18) in the 7 lesions with energy density between 400 and 460 calories/cm(3). All animals survived the surgeries, and no device-related complications were identified during the study. No acute renal failure was identified in analysis of the blood work. CONCLUSION: A novel 12-mm laparoscopic HIFU probe was successfully calibrated for the ablation of porcine renal tissue. The safety profile of the Sonatherm probe was found to be excellent with no complications identified.

High-intensity focused ultrasound surgery of the brain: part 1--A historical perspective with modern applications.

The field of magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

High intensity focused ultrasound renal tissue ablation: a laparoscopic porcine model.

PURPOSE: High intensity focused ultrasound for renal lesions is still experimental. In a porcine model we evaluated the safety and efficacy of a newly designed laparoscopic high intensity focused ultrasound probe and software that allows real-time ultrasound guidance during renal tissue ablation. MATERIALS AND METHODS: A Sonatherm 600 high intensity focused ultrasound system with a newly designed laparoscopic high intensity focused ultrasound probe was used through a standard Endopath 18 mm port. A total of 16 lesions were created in 15 kidneys in a total of 8 animals and randomized into 2 groups, including acute with sacrifice 4 days postoperatively and subacute with sacrifice 14 days postoperatively. Lesion size and location varied for each surgical procedure to simulate various treatment scenarios. RESULTS: Mean +/- SD planned ablation volume was 7.1 +/- 5.1 cc and mean treatment time was 7.2 +/- 06.88 minutes. For all lesions an injury volume was observed with a central zone of complete necrosis and no viable tissue. Mean total injury volume was 6.5 + 3.5 cc (range 1.1 to 13.7), comparable to preoperative mean planned ablation volume (p = 0.84). Mean necrosis volume was 4.89 +/- 2.9 cc (range 0.8 to 10.5), appreciably lower than preoperative mean planned ablation volume (p = 0.33). Presence of the collecting system interposed with the treatment region did not impact the injury volume-to-planned ablation volume ratio or the necrosis volume-to-planned ablation volume ratio. No animals died before study completion. Two intraoperative complications occurred, including a back wall musculature burn and a ureteral burn. CONCLUSIONS: Laparoscopic high intensity focused ultrasound for renal tissue using the newly developed probe was feasible and efficacious. The ability to perform renal high intensity focused ultrasound through an 18 mm laparoscopic port offers a new alternative for renal tumor ablation.

Phase I/II trial of high intensity focused ultrasound for the treatment of previously untreated localized prostate cancer.

PURPOSE: We examined the safety and potential efficacy of transrectally delivered high intensity focused ultrasound for the full gland ablation of previously untreated localized prostate cancer. MATERIALS AND METHODS: A total of 20 patients with localized prostate cancer underwent 1 to 3 high intensity focused ultrasound treatments of the prostate. The primary outcome was safety and the secondary outcomes were prostate specific antigen, prostate biopsy and quality of life measures. RESULTS: A total of 19 patients had complete followup. Serious adverse events related to treatment were limited with the most common adverse event being transient urinary retention more than 30 days in duration in only 10% of patients. Rectal injury occurred in 1 patient. With 1 to 3 treatments 42% of the patients achieved prostate specific antigen less than 0.5 ng/ml and a negative prostate biopsy. CONCLUSIONS: High intensity focused ultrasound in patients with previously untreated prostate cancer is generally well tolerated and it has the potential to completely ablate the prostate gland. With further refinement of the optimal treatment dose and technique this technology has the potential to be an effective form of therapy for localized prostate cancer.

Modeling prostate anatomy from multiple view TRUS images for image-guided HIFU therapy.

Current planning methods for transrectal high-intensity focused ultrasound treatment of prostate cancer rely on manually defining treatment regions in 15-20 sector transrectal ultrasound (TRUS) images of the prostate. Although effective, it is desirable to reduce user interaction time by identifying functionally related anatomic structures (segmenting), then automatically laying out treatment sites using these structures as a guide. Accordingly, a method has been developed to effectively generate solid three-dimensional (3-D) models of the prostate, urethra, and rectal wall from boundary trace data. Modeling the urethra and rectal wall are straightforward, but modeling the prostate is more difficult and has received much attention in the literature. New results presented here are aimed at overcoming many of the limitations of previous approaches to modeling the prostate while using boundary traces obtained via manual tracing in as few as 5 sector and 3 linear images. The results presented here are based on a new type of surface, the Fourier ellipsoid, and the use of sector and linear TRUS images. Tissue-specific 3-D models will ultimately permit finer control of energy deposition and more selective destruction of cancerous regions while sparing critical neighboring structures.

Laparoscopic partial kidney ablation with high intensity focused ultrasound.

PURPOSE: High intensity focused ultrasound has been performed for transrectal and extracorporeal thermal ablation of tissues. We developed and tested a laparoscopic probe that allows real-time ultrasound imaging during partial renal ablation using high intensity focused ultrasound. METHODS: A Sonablate 200 (Focus Surgery, Indianapolis, Indiana) high intensity focused ultrasound system with a modified 18 mm. laparoscopic probe was used in all experiments. In 13 Yucatan mini-pigs a 5Fr ureteral catheter was inserted into the renal pelvis and 10 cc air were instilled into the collecting system. The kidney was laparoscopically dissected, the high intensity focused ultrasound probe was inserted through a 33 mm. laparoscopic port and the targeted renal pole was treated. RESULTS: Renal lesions were created in 12 of 13 treated kidneys under real-time ultrasound visualization. Median operative time was 180 minutes, average high intensity focused ultrasound activation time was 18.3 minutes and lesion size was 23 x 17 x 11 mm. At 4 and 14 days 4 (acute group) and 6 (subacute group) animals were available for renal functional and anatomical evaluation, respectively. No difference in renal function was seen in treated and untreated kidneys. Pathological examination at 14 days revealed homogenous and complete tissue necrosis throughout the whole volume of the lesion with sharp demarcation from adjacent normal tissue. CONCLUSIONS: We were able to refine a probe for laparoscopic high intensity focused ultrasound delivery capable of simultaneous ultrasound imaging. Partial renal ablation using this probe is feasible and safe, and resulted in homogenous, complete and reproducible lesions.

Transrectal high-intensity focused ultrasound for treatment of patients with stage T1b-2n0m0 localized prostate cancer: a preliminary report.

OBJECTIVES: To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue. METHODS: We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed. RESULTS: A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention. CONCLUSIONS: Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.