Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard.
ABSTRACT: PURPOSE:We evaluated magnetic resonance imaging controlled transurethral ultrasound therapy as a treatment for magnetic resonance imaging defined focal prostate cancer using subsequent prostatectomy and histology as the reference standard. MATERIALS AND METHODS:Five men completed this pilot study, which was approved by the institutional review board. Prior to radical prostatectomy focal tumors identified by magnetic resonance imaging were treated by coagulating targeted subtotal 3-dimensional volumes of prostate tissue using magnetic resonance imaging controlled transurethral focused ultrasound. Treatment was performed with a 3 Tesla clinical magnetic resonance imaging unit combined with modified clinical planning software for high intensity focused ultrasound therapy. After prostatectomy whole mount histological sections parallel to the magnetic resonance imaging treatment planes were used to compare magnetic resonance imaging measurements with thermal damage at the cellular level and, thus, evaluate treatment and target accuracy. RESULTS:Three-dimensional target volumes of 4 to 20 cc and with radii up to 35 mm from the urethra were treated successfully. Mean ± SD temperature control accuracy at the target boundary was -1.6 ± 4.8C and the mean spatial targeting accuracy achieved was -1.5 ± 2.8 mm. Mean treatment accuracy with respect to histology was -0.4 ± 1.7 mm with all index tumors falling inside the histological outer limit of thermal injury. CONCLUSIONS:Magnetic resonance imaging guided transurethral ultrasound therapy is capable of generating thermal coagulation and tumor destruction in targeted 3-dimensional angular sectors out to the prostate capsule for prostate glands up to 70 cc in volume. Ultrasound parameters needed to achieve ablation at the prostate capsule were determined, providing a foundation for future studies.
Project description: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.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).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.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.
Project description:We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology.A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point.Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy.In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to 65%). If confirmed, these results will have important clinical implications.
Project description:BACKGROUND:The diagnostic pathway for prostate cancer (PCa) is advancing towards an imaging-driven approach. Multiparametric magnetic resonance imaging, although increasingly used, has not shown sufficient accuracy to replace biopsy for now. The introduction of new ultrasound (US) modalities, such as quantitative contrast-enhanced US (CEUS) and shear wave elastography (SWE), shows promise but is not evidenced by sufficient high quality studies, especially for the combination of different US modalities. The primary objective of this study is to determine the individual and complementary diagnostic performance of greyscale US (GS), SWE, CEUS and their combination, multiparametric ultrasound (mpUS), for the detection and localization of PCa by comparison with corresponding histopathology. METHODS/DESIGN:In this prospective clinical trial, US imaging consisting of GS, SWE and CEUS with quantitative mapping on 3 prostate imaging planes (base, mid and apex) will be performed in 50 patients with biopsy-proven PCa before planned radical prostatectomy using a clinical ultrasound scanner. All US imaging will be evaluated by US readers, scoring the four quadrants of each imaging plane for the likelihood of significant PCa based on a 1 to 5 Likert Scale. Following resection, PCa tumour foci will be identified, graded and attributed to the imaging-derived quadrants in each prostate plane for all prostatectomy specimens. Primary outcome measure will be the sensitivity, specificity, negative predictive value and positive predictive value of each US modality and mpUS to detect and localize significant PCa evaluated for different Likert Scale thresholds using receiver operating characteristics curve analyses. DISCUSSION:In the evaluation of new PCa imaging modalities, a structured comparison with gold standard radical prostatectomy specimens is essential as first step. This trial is the first to combine the most promising ultrasound modalities into mpUS. It complies with the IDEAL stage 2b recommendations and will be an important step towards the evaluation of mpUS as a possible option for accurate detection and localization of PCa. TRIAL REGISTRATION:The study protocol for multiparametric ultrasound was prospectively registered on Clinicaltrials.gov on 14 March 2017 with the registry name 'Multiparametric Ultrasound-Study for the Detection of Prostate Cancer' and trial registration number NCT03091231.
Project description:PURPOSE:We report our initial experience with whole body and dedicated prostate magnetic resonance imaging as a single examination to assess local recurrence and metastatic disease in patients with suspected recurrent prostate cancer after radical prostatectomy. MATERIALS AND METHODS:In this institutional review board approved, retrospective, single center study 76 consecutive patients with clinically suspected recurrent prostate cancer following radical prostatectomy underwent combined whole body and dedicated prostate magnetic resonance imaging at a single session from October 2014 to January 2016. Scans were evaluated to detect disease in the prostate bed and regional nodes, and at distant sites. Comparison was made to other imaging tests, and prostate bed, node and bone biopsies performed within 90 days. RESULTS:Whole body and dedicated prostate magnetic resonance imaging was completed successfully in all patients. Median prostate specific antigen was 0.36 ng/ml (range less than 0.05 to 56.12). Whole body and dedicated prostate magnetic resonance imaging identified suspected disease recurrence in 16 of 76 patients (21%), including local recurrence in the radical prostatectomy bed in 6, nodal metastases in 3, osseous metastases in 4 and multifocal metastatic disease in 3. In 43 patients at least 1 standard staging scan was done in addition to whole body and dedicated prostate magnetic resonance imaging. Concordance was demonstrated between the imaging modalities in 36 of 43 cases (84%). All metastatic lesions detected by other imaging tests were detected on magnetic resonance imaging. In addition, the magnetic resonance imaging modality detected osseous metastases in 4 patients with false-negative findings on other imaging tests, including 2 bone scans and 3 computerized tomography scans. It also excluded osseous disease in 1 patient with positive 18F-fluorodeoxyglucose positron emission tomography/computerized tomography and subsequent negative bone biopsy. CONCLUSIONS:Combined whole body and dedicated prostate magnetic resonance imaging is feasible in a clinical practice setting. It can provide incremental information compared to standard imaging in men with suspected prostate cancer recurrence after radical prostatectomy.
Project description:PURPOSE:We assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy. MATERIALS AND METHODS:Subjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings. RESULTS:Of the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology. CONCLUSIONS:Using intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility.
Project description:The treatment of low-risk prostate cancer is a common clinical dilemma between standard curative whole gland therapy (and its associated quality of life diminishing side effects) and active surveillance (and its low, but real, risk of progression). The goal of focal therapy in low-risk prostate cancer is to achieve the best balance between cancer control and maintenance of quality of life. Magnetic resonance-guided focused ultrasound (MRgFUS) surgery is a non-invasive thermal ablation method that integrates magnetic resonance imaging for target identification, treatment planning and closed-loop control of thermal deposition and focused ultrasound for thermal ablation of the tumour target. This novel transrectal system allows for tumour localization, targeting and monitoring of tumour target ablation in real time, while simultaneously preserving adjacent normal tissue thereby minimizing the side effects of standard curative surgical or radiation therapy. We report the first North American clinical experience of treatment of localized prostate cancer with focal MR-guided transrectal focused ultrasound (clinicaltrial.gov identifier NCT01226576).
Project description:Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy.Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen.At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out.Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy.
Project description:Laser prostatectomy has increased in popularity in the last decade. However, traditional transurethral resection of the prostate remains common. To understand decisions about the use of laser prostatectomy vs transurethral prostate resection, we evaluated trends in transurethral surgery for benign prostatic hyperplasia in an all payer data set, focusing on patient and provider factors associated with the receipt of laser prostatectomy.Using Florida State Inpatient Database and Ambulatory Surgery Database, we identified patients who underwent laser prostatectomy or transurethral prostate resection from 2001 to 2009. We calculated surgery rates with time, stratified by procedure type. We used multilevel regression to examine patient (age, race and comorbidity level) and provider (surgeon volume) factors associated with the receipt of laser prostatectomy vs transurethral prostate resection.While the overall rates of transurethral surgery remained stable during the study period (p = 0.227), laser prostatectomy use increased 400% from 25 to 114 procedures per 100,000 men (p <0.001), replacing about half of all transurethral prostate resections. Patients were less likely to undergo laser prostatectomy if they were older (OR 0.65, 95% CI 0.61-0.70) and less healthy (OR 0.48, 95% CI 0.45-0.51). While these factors were predictive of surgery type, most of the variation in laser prostatectomy use (69%) was determined by the urologist seen by the patient.Laser prostatectomy use has increased in the last decade at the expense of transurethral prostate resection, driven largely by provider effects. However, elderly and more infirm patients are least likely to undergo it, raising concern about underuse in this population.
Project description:Ultrasound can penetrate deep into tissues and interact with human tissue via thermal and mechanical mechanisms. The ability to focus an ultrasound beam and its energy onto millimeter-size targets was a significant milestone in the development of therapeutic applications of focused ultrasound. Focused ultrasound can be used as a non-invasive thermal ablation technique for tumor treatment and is being developed as an option to standard oncologic therapies. High-intensity focused ultrasound has now been used for clinical treatment of a variety of solid malignant tumors, including those in the pancreas, liver, kidney, bone, prostate, and breast, as well as uterine fibroids and soft-tissue sarcomas. Magnetic resonance imaging and Ultrasound imaging can be combined with high intensity focused ultrasound to provide real-time imaging during ablation. Magnetic resonance guided focused ultrasound represents a novel non-invasive method of treatment that may play an important role as an alternative to open neurosurgical procedures for treatment of a number of brain disorders. This paper briefly reviews the underlying principles of HIFU and presents current applications, outcomes, and complications after treatment. Recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed, along with clinical challenges and potential future clinical applications of HIFU.
Project description:PURPOSE:In this study, the efficacy of transurethral prostate ablation in the presence of silica-shell ultrasound-triggered phase-shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated. METHODS:sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2 O3 , to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1 contrast, and temperature. In addition, non-perfused areas (NPAs) on dynamic contrast-enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43 ) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology. RESULTS:For treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96-0.99, 0.98-0.99, and 0.91-0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion-weighted imaging (P = 0.005) were apparent in lesions with thermal fixation. CONCLUSIONS:T1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.