MRI-guided Focused Ultrasound Ablation for Localized Intermediate-Risk Prostate Cancer: Early Results of a Phase II Trial.

Background To reduce adverse effects of whole-gland therapy, participants with localized clinically significant prostate cancer can undergo MRI-guided focal therapy. Purpose To explore safety and early oncologic and functional outcomes of targeted focal high-intensity focused ultrasound performed under MRI-guided focused ultrasound for intermediate-risk clinically significant prostate cancer. Materials and Methods In this prospective phase II trial, between February 2016 and July 2019, men with unifocal clinically significant prostate cancer visible at MRI were treated with transrectal MRI-guided focused ultrasound. The primary end point was the 5-month biopsy (last recorded in December 2019) with continuation to the 24-month follow-up projected to December 2021. Real-time ablation monitoring was performed with MR thermography. Nonperfused volume was measured at treatment completion. Periprocedural complications were recorded. Follow-up included International Prostate Symptom Score (IPSS) and International Index of Erectile Function-15 (IIEF-15) score at 6 weeks and 5 months, and multiparametric MRI and targeted biopsy of the treated area at 5 months. The generalized estimating equation model was used for statistical analysis, and the Holm method was used to adjust P value. Results Treatment was successfully completed in all 44 men, 36 with grade group (GG) 2 and eight with GG 3 disease (median age, 67 years; interquartile range [IQR], 62-70 years). No major treatment-related adverse events occurred. Forty-one of 44 participants (93%; 95% CI: 82, 98) were free of clinically significant prostate cancer (≥6 mm GG 1 disease or any volume ≥GG 2 disease) at the treatment site at 5-month biopsy (median, seven cores). Median IIEF-15 and IPSS scores were similar at baseline and at 5 months (IIEF-15 score at baseline, 61 [IQR, 34-67] and at 5 months, 53 [IQR, 24-65.5], P = .18; IPSS score at baseline, 3.5 [IQR, 1.8-7] and at 5 months, 6 [IQR, 2-7.3], P = .43). Larger ablations (≥15 cm3) compared with smaller ones were associated with a decline in IIEF-15 scores at 6 weeks (adjusted P < .01) and at 5 months (adjusted P = .07). Conclusion Targeted focal therapy of intermediate-risk prostate cancer performed with MRI-guided focused ultrasound ablation was safe and had encouraging early oncologic and functional outcomes. © RSNA, 2021 Online supplemental material is available for this article See also the editorial by Tempany-Afdhal in this issue.

Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Magnetic resonance guided focused high frequency ultrasound ablation for focal therapy in prostate cancer - phase 1 trial.

OBJECTIVES: To evaluate the feasibility and safety of focal therapy for low-intermediate risk prostate cancer (PCa) with magnetic resonance-guided high frequency focused ultrasound (MRgFUS) METHODS: This IRB-approved phase 1 prospective study enrolled eight patients with prostate specific antigen (PSA) ≤ 10 ng/ml, ≤ cT2a and Gleason score ≤ 7 (4 + 3) disease following informed consent. Under MRI guidance, focused high frequency ultrasound energy was delivered to ablate the target tissue. Treatment-related adverse events were recorded. Oncologic outcomes were evaluated with multiparametric MRI, PSA and TRUS biopsy at 6 months following treatment. RESULTS: Ten target lesions [six Gleason 6 lesions, two Gleason 7 (3 + 4) and two Gleason 7 (4 + 3)] were treated in eight men (prostate volume range, 25-50 cc; mean MRI time, 248 min per patient; mean sonication duration, 65 min). Mean target volume was 2.7 cc and mean post-treatment non-perfused volume was 4.3 cc. Quality of life parameters were similar between baseline and 6 months in 6/8 patients. All treated regions were negative on MRI; 4/8 patients and 6/10 target lesions (60%) were clear of disease on biopsy. One patient with 2-mm Gleason 8 disease in one of five cores from treatment site (4 + 3 disease at baseline) subsequently underwent prostatectomy with negative surgical margins. Three patients with low volume (5-15%) Gleason 6 residual disease were offered active surveillance. Mean PSA decreased from 5.06 at baseline to 3.4 ng/ml at 6 months. CONCLUSION: MRgFUS is a feasible and safe method of noninvasively ablating low-intermediate risk PCa with acceptable short-term oncologic outcomes. KEY POINTS: • Focal therapy selectively ablates locally confined, clinically significant index lesion with a margin while sparing rest of gland and adjacent vital structures. • Magnetic resonance-guided focused high frequency ultrasound surgery (MRgFUS) combines MRI with HIFU. • MRgFUS provides ability to monitor treatments in real time and allows a targeted approach for focal ablation. • MRgFUS is a feasible, safe method of noninvasively ablating low-intermediate risk PCa. • MRgFUS provides acceptable oncologic outcomes at 6 months.

Mechatronic system for in-bore MRI-guided insertion of needles to the prostate: An in vivo needle guidance accuracy study.

BACKGROUND: To present our experiences in initial clinical evaluation of a novel mechatronic system for in-bore guidance of needles to the prostate for MRI-guided prostate interventions in 10 patients. We report accuracy of this device in the context of focal laser ablation therapy for localized prostate cancer. METHODS: An MRI-compatible needle guidance device was developed for transperineal prostate interventions. Ten patients underwent MRI-guided focal laser ablation therapy with device-mediated laser fiber delivery. We recorded needle guidance error and needle delivery time. RESULTS: A total of 37 needle insertions were evaluated. Median needle guidance error was 3.5 mm (interquartile range, 2.1-5.4 mm), and median needle delivery time was 9 min (interquartile range, 6.5-12 min). CONCLUSION: This system provides a reliable method of accurately aligning needle guides for in-bore transperineal needle delivery to the prostate.

Real-Time MRI-Guided Focused Ultrasound for Focal Therapy of Locally Confined Low-Risk Prostate Cancer: Feasibility and Preliminary Outcomes.

OBJECTIVE: Focal therapy is an emerging approach to the treatment of localized prostate cancer. The purpose of this study was to report the 6-month follow-up oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound in North America. SUBJECTS AND METHODS: Four patients with a prostate-specific antigen (PSA) level of 10 ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 + 3) were prospectively enrolled in the study and underwent multiparametric MRI and transrectal ultrasound-guided prostate systematic biopsy. Under MRI guidance and real-time monitoring with MR thermography, focused high-frequency ultrasound energy was delivered to ablate the target tissue. The incidence and severity of treatment-related adverse events were recorded along with responses to serial quality-of-life questionnaires for 6 months after treatment. Oncologic outcomes were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided biopsy 6 months after treatment. RESULTS: Four patients with a total of six target lesions were treated and had complications graded Clavien-Dindo I or less. Quality-of-life parameters were similar between baseline and 6-months. All four patients had normal MRI findings in the treated regions (100%), biopsy showed that three patients (75%) were clear of disease in the treated regions, representing complete ablation of five target lesions (83%). All patients had at least one Gleason 6-positive core outside of the treated zone. CONCLUSION: MRI-guided focused ultrasound is a feasible method of noninvasively ablating low-risk prostate cancers with low morbidity. Further investigation and follow-up are warranted in a larger patient series with appropriate statistical analysis of oncologic and functional outcome measures.

Optimizing contrast agent concentration and spoiled gradient echo pulse sequence parameters for catheter visualization in MR-guided interventional procedures: an analytic solution.

PURPOSE: A critical requirement of MR-guided interventions is the visualization of an instrument (e.g., catheter, needle) during the procedure. One approach is to fill the instrument with a contrast agent. Previously, the optimization of contrast agent visualization was performed only empirically. In the present study, an analytic optimization of contrast agent SNR efficiency was performed for a spoiled gradient echo pulse sequence. METHODS: Optimal flip angle, repetition time, echo time, and contrast agent concentration were derived analytically. The solution is valid for any contrast agent, provided the relationship between T1 , T2 , and doping concentration is known. RESULTS: Phantom experiments validated the analytic optimization for Gd- and MnCl2 -based contrast agents. Results showed excellent agreement between experimentally predicted and theoretically observed magnetization behavior. In vivo experiments demonstrated optimized contrast agent visualization in brain, heart, and prostate applications. The results demonstrated the large SNR that can be achieved with analytic optimization. As a practical guideline, an 11% dilution of 500 mMol/L Gd-DTPA solution, repetition time ≈ 4 ms, echo time ≈ 1 ms, and θ ≈ 65° was found to provide a large SNR. CONCLUSION: This study derived and validated a method for analytically optimizing contrast agent SNR efficiency. This information may be useful for visualizing instruments during MR-guided interventions.

Construction and evaluation of an anatomically correct multi-image modality compatible phantom for prostate cancer focal ablation.

PURPOSE: Focal therapy using lasers is emerging as an alternative strategy for prostate cancer treatment. However, to our knowledge no anatomically correct models are available to test imaging and ablation techniques. Animal models present ethical, anatomical and cost challenges. We designed and validated an inexpensive but anatomically correct prostate phantom incorporating tumor, rectum and urethra that can be used for simulated and experimental magnetic resonance guided focal intervention. Our secondary aim was to asses the phantom using other imaging modalities. MATERIALS AND METHODS: The phantom, which was constructed of ballistic gel, includes an 80 gm prostate with urethra, tumor, perineum and rectum. Gadolinium was added to make the gel visible to magnetic resonance imaging. To recreate a tumor an irregularly shaped 5 cc volume of coagulable gel was inserted into the prostate phantom. The phantom was evaluated using magnetic resonance, computerized tomography and transrectal ultrasound. Thermal ablation was delivered via interstitial placement of laser fibers. Magnetic resonance thermometry was done to record real-time tissue temperatures during thermal ablation. RESULTS: With all modalities tested the phantom emulated human prostate anatomy. The coagulable gel tumor allowed us to generate focal thermal lesions. The phantom had magnetic resonance imaging properties comparable to in vivo properties, allowing ablative zones to be accurately assessed and magnetic resonance thermometry to be done. CONCLUSIONS: The phantom is a useful tool to test different aspects of thermal focal ablation for prostate cancer using multiple imaging modalities, particularly magnetic resonance. It is inexpensive and easily constructed, and may be considered a valuable model to train on and teach focal therapy.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences.

OBJECTIVE: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research. METHODS: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed. RESULTS: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event. CONCLUSIONS: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes.

OBJECTIVE: To report the 6-month single-blinded results of unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor. METHODS: Three patients with tremor due to Parkinson disease, 2 with dystonic tremor in the context of cervicobrachial dystonia and writer's cramp, and 1 with dystonia gene-associated tremor underwent MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere. The primary endpoint was the reduction of lateralized items of the Tremor Rating Scale of contralateral hemibody assessed by a blinded rater. RESULTS: All patients achieved a statistically significant, immediate, and sustained improvement of the contralateral tremor score by 42.2%, 52.0%, 55.9%, and 52.9% at 1 week and 1, 3, and 6 months after the procedure, respectively. All patients experienced transient side effects and 2 patients experienced persistent side effects at the time of last evaluation: hemitongue numbness and hemiparesis with hemihypoesthesia. CONCLUSIONS: Vim MRgFUS is a promising, incision-free, but nevertheless invasive technique to effectively treat tremors other than essential tremor. Future studies on larger samples and longer follow-up will further define its effectiveness and safety. CLINICALTRIALSGOV IDENTIFIER: NCT02252380. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with tremor not caused by essential tremor, MRgFUS of the Vim improves the tremor of the contralateral hemibody at 6 months.

Focal magnetic resonance guided focused ultrasound for prostate cancer: Initial North American experience.

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).

Focal laser ablation for prostate cancer followed by radical prostatectomy: validation of focal therapy and imaging accuracy.

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

Real-time magnetic resonance imaging-guided focal laser therapy in patients with low-risk prostate cancer.

Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)-guided focal laser ablation. The tumor was identified on MRI. A laser fiber was delivered via a catheter inserted through a perineal template and guided to the target with MRI. The tissue temperature was monitored during laser ablation by MRI thermometry. Accumulated thermal damage was calculated in real time. Immediate post-treatment contrast-enhanced MRI confirmed devascularization of the target. No adverse events were noted. MRI-guided focal laser therapy of low-risk PCa is feasible and may offer a good balance between cancer control and side effects.