Nested Semi-Transparent Isosurface Simulated Volume-Rendering (NESTIS-VR) - An efficient on-device rendering approach for Augmented Reality headsets increasing surgeon confidence of kidney donor arterial anatomy.

BACKGROUND AND OBJECTIVE: Volume-renderings of computed tomography or magnetic resonance angiograms (MRAs) are routinely used by surgeons in the preoperative assessment of vascular anatomy in kidney donors. Stereoscopic headsets (OST-HMD) like Microsoft HoloLens allow intuitive interaction with three-dimensional content for more intuitive comprehension, but do not allow real-time ray-casting volume-rendering of medical volume datasets on-device due to computational limitations. METHODS: We introduce NEsted Semi-Transparent Isosurface Simulated Volume-Rendering (NESTIS-VR), as an on-device alternative to ray-casting volume-rendering and developed an application for HoloLens to render kidney donor MRAs with interactive control of fundamental rendering parameters. We compared NESTIS-VR with current standard pre-calculated 2D ray-cast volume-renderings in an observational study with 2 expert kidney transplant surgeons, measuring their confidence in pre-operatively assessing the kidney pedicle arterial anatomy in 20 potential donors. We also compared it against other 3D rendering techniques to understand which features contributed most to any improvements. RESULTS: Real-time stereoscopic three-dimensional (3D) NESTIS-VR in Augmented Reality significantly improves surgeons' confidence compared with pre-calculated conventional two-dimensional (2D) ray-casting volume-rendered images (p = 0.0415/p = 0.00003). 2D non-stereoscopic NESTIS-VR was significantly superior to pre-calculated 2D ray-casting volume-rendered images for both surgeons (p = 0.044/p = 0.0003). Single isosurface 2D rendering was significantly superior than pre-calculated 2D volume-rendered images for one surgeon. There was no significant difference between binocular 3D display over 2D views with NESTIS-VR or between constrained and unconstrained vantage points for 2D viewing. CONCLUSION: NESTIS-VR provides a new approach to rendering medical datasets in computationally limited OST-HMD headsets and significantly increases surgeons' confidence of kidney donor arterial anatomy. The principal confidence benefit arises from providing surgeons interactive control over rendering parameters compared to pre-calculated renderings at preset parameters whilst rendering on-device and keeping the OST-HMD untethered from a workstation.

Intraprocedural Diffusion-weighted Imaging for Predicting Ablation Zone during MRI-guided Focused Ultrasound of Prostate Cancer.

Purpose To compare diffusion-weighted imaging (DWI) with thermal dosimetry as a noncontrast method to predict ablation margins in individuals with prostate cancer treated with MRI-guided focused ultrasound (MRgFUS) ablation. Materials and Methods This secondary analysis of a prospective trial (ClinicalTrials.gov no. NCT01657942) included 17 participants (mean age, 64 years ± 6 [SD]; all male) who were treated for prostate cancer using MRgFUS in whom DWI was performed immediately after treatment. Ablation contours from computed thermal dosimetry and DWI as drawn by two blinded radiologists were compared against the reference standard of ablation assessment, posttreatment contrast-enhanced nonperfused volume (NPV) contours. The ability of each method to predict the ablation zone was analyzed quantitively using Dice similarity coefficients (DSCs) and mean Hausdorff distances (mHDs). Results DWI revealed a hyperintense rim at the margin of the ablation zone. While DWI accurately helped predict treatment margins, thermal dose contours underestimated the extent of the ablation zone compared with the T1-weighted NPV imaging reference standard. Quantitatively, contour assessment between methods showed that DWI-drawn contours matched postcontrast NPV contours (mean DSC = 0.84 ± 0.05 for DWI, mHD = 0.27 mm ± 0.13) better than the thermal dose contours did (mean DSC = 0.64 ± 0.12, mHD = 1.53 mm ± 1.20) (P < .001). Conclusion This study demonstrates that DWI, which can visualize the ablation zone directly, is a promising noncontrast method that is robust to treatment-related bulk motion compared with thermal dosimetry and correlates better than thermal dosimetry with the reference standard T1-weighted NPV. Keywords: Interventional-Body, Ultrasound-High-Intensity Focused (HIFU), Genital/Reproductive, Prostate, Oncology, Imaging Sequences, MRI-guided Focused Ultrasound, MR Thermometry, Diffusionweighted Imaging, Prostate Cancer ClinicalTrials.gov Identifier no. NCT01657942 Supplemental material is available for this article. © RSNA, 2024.

Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial.

Importance: Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective: To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants: This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention: A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures: Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results: The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance: Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration: ClinicalTrials.gov Identifier NCT04112381.

RAPHIA: A deep learning pipeline for the registration of MRI and whole-mount histopathology images of the prostate.

Image registration can map the ground truth extent of prostate cancer from histopathology images onto MRI, facilitating the development of machine learning methods for early prostate cancer detection. Here, we present RAdiology PatHology Image Alignment (RAPHIA), an end-to-end pipeline for efficient and accurate registration of MRI and histopathology images. RAPHIA automates several time-consuming manual steps in existing approaches including prostate segmentation, estimation of the rotation angle and horizontal flipping in histopathology images, and estimation of MRI-histopathology slice correspondences. By utilizing deep learning registration networks, RAPHIA substantially reduces computational time. Furthermore, RAPHIA obviates the need for a multimodal image similarity metric by transferring histopathology image representations to MRI image representations and vice versa. With the assistance of RAPHIA, novice users achieved expert-level performance, and their mean error in estimating histopathology rotation angle was reduced by 51% (12 degrees vs 8 degrees), their mean accuracy of estimating histopathology flipping was increased by 5% (95.3% vs 100%), and their mean error in estimating MRI-histopathology slice correspondences was reduced by 45% (1.12 slices vs 0.62 slices). When compared to a recent conventional registration approach and a deep learning registration approach, RAPHIA achieved better mapping of histopathology cancer labels, with an improved mean Dice coefficient of cancer regions outlined on MRI and the deformed histopathology (0.44 vs 0.48 vs 0.50), and a reduced mean per-case processing time (51 vs 11 vs 4.5 min). The improved performance by RAPHIA allows efficient processing of large datasets for the development of machine learning models for prostate cancer detection on MRI. Our code is publicly available at: https://github.com/pimed/RAPHIA.

MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

OBJECTIVE: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids. METHODS: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded. RESULTS: The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns. CONCLUSION: MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis. CLINICAL RELEVANCE STATEMENT: Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely. KEY POINTS: • Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

High-Intensity Focused Ultrasound Surgery for Tumor Ablation: A Review of Current Applications.

The management of cancer with alternative approaches is a matter of clinical interest worldwide. High-intensity focused ultrasound (HIFU) surgery is a noninvasive technique performed under US or MRI guidance. The most studied therapeutic uses of HIFU involve thermal tissue ablation, demonstrating both palliative and curative potential. However, concurrent mechanical bioeffects also provide opportunities in terms of augmented drug delivery and immunosensitization. The safety and efficacy of HIFU integration with current cancer treatment strategies are being actively investigated in managing primary and secondary tumors, including cancers of the breast, prostate, pancreas, liver, kidney, and bone. Current primary HIFU indications are pain palliation, complete ablation of localized earlystage tumors, or debulking of unresectable late-stage cancers. This review presents the latest HIFU applications, from investigational to clinically approved, in the field of tumor ablation. Keywords: Ultrasound, Ultrasound-High Intensity Focused (HIFU), Interventional-MSK, Interventional-Body, Oncology, Technology Assessment, Tumor Response, MR Imaging © RSNA, 2023.

What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

Immunoglobulin G4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis.

Immunoglobulin G4-seronegative autoimmune cholangiopathy is a rare cause of biliary strictures. We describe a 27-year-old man presenting with elevated liver enzymes, recurrent cholangitis/bacteremia, biliary strictures, and normal immunoglobulin G4 levels, who was initially diagnosed with primary sclerosing cholangitis, and later listed for transplantation for recurrent bacteremia. Subsequent surveillance imaging demonstrated morphologic changes consistent with biliary strictures and autoimmune pancreatitis. Initiating corticosteroids resulted in liver enzyme normalization and stricture improvement. Diagnosing seronegative autoimmune cholangiopathy remains challenging given similar presentation to primary sclerosing cholangitis. This case highlights importance of a wide differential for biliary strictures, with increased suspicion in those developing pancreatic changes in this setting.

CT-guided Pulsed Radiofrequency Combined with Steroid Injection for Sciatica from Herniated Disk: A Randomized Trial.

Background Evidence regarding effective nonsurgical management of sciatica remains limited. Purpose To determine a difference in effectiveness between combined pulsed radiofrequency (PRF) and transforaminal epidural steroid injection (TFESI) treatment versus TFESI alone for sciatic pain due to lumbar disk herniation. Materials and Methods This prospective multicenter double-blind randomized clinical trial was conducted between February 2017 and September 2019 in participants with sciatica due to lumbar disk herniation lasting 12 weeks or longer that was not responsive to conservative treatment. Study participants were randomly assigned to undergo one CT-guided treatment with combined PRF and TFESI (n = 174) or TFESI alone (n = 177). The primary outcome was leg pain severity, as assessed with the numeric rating scale (NRS) (range, 0-10) at weeks 1 and 52 after treatment. Secondary outcomes included Roland-Morris Disability Questionnaire (RMDQ) score (range, 0-24) and Oswestry Disability Index (ODI) score (range, 0-100). Outcomes were analyzed according to the intention-to-treat principle via linear regression. Results Mean age of the 351 participants (223 men) was 55 years ± 16 (SD). At baseline, NRS was 8.1 ± 1.1 in the PRF and TFESI group and 7.9 ± 1.1 in the TFESI group. NRS was 3.2 ± 0.2 in the PRF and TFESI group and 5.4 ± 0.2 in the TFESI group (average treatment effect, 2.3; 95% CI: 1.9, 2.8; P < .001) at week 1 and 1.0 ± 0.2 and 3.9 ± 0.2 (average treatment effect, 3.0; 95% CI: 2.4, 3.5; P < .001), respectively, at week 52. At week 52, the average treatment effect was 11.0 (95% CI: 6.4, 15.6; P < .001) for ODI and 2.9 (95% CI: 1.6, 4.3; P < .001) for RMDQ, favoring the combined PRF and TFSEI group. Adverse events were reported in 6% (10 of 167) of participants in the PRF and TFESI group and in 3% (six of 176) of participants in the TFESI group (eight participants did not complete follow-up questionnaires). No severe adverse events occurred. Conclusion In the treatment of sciatica caused by lumbar disk herniation, pulsed radiofrequency combined with transforaminal epidural steroid injection is more effective for pain relief and disability improvement than steroid injection alone. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Jennings in this issue.

Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Focused Ultrasound and External Beam Radiation Therapy for Painful Bone Metastases: A Phase II Clinical Trial.

Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, χ2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms (P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) (P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT (P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 (P < .001), respectively. QLQ-C15-PAL for physical function (P = .002), appetite (P < .001), nausea and vomiting (P < .001), dyspnea (P < .001), and QoL (P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kelekis in this issue.

Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial. METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported. RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported. CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

The Association of Tissue Change and Treatment Success During High-intensity Focused Ultrasound Focal Therapy for Prostate Cancer.

BACKGROUND: Tissue preservation strategies have been increasingly used for the management of localized prostate cancer. Focal ablation using ultrasound-guided high-intensity focused ultrasound (HIFU) has demonstrated promising short and medium-term oncological outcomes. Advancements in HIFU therapy such as the introduction of tissue change monitoring (TCM) aim to further improve treatment efficacy. OBJECTIVE: To evaluate the association between intraoperative TCM during HIFU focal therapy for localized prostate cancer and oncological outcomes 12 mo afterward. DESIGN, SETTING, AND PARTICIPANTS: Seventy consecutive men at a single institution with prostate cancer were prospectively enrolled. Men with prior treatment, metastases, or pelvic radiation were excluded to obtain a final cohort of 55 men. INTERVENTION: All men underwent HIFU focal therapy followed by magnetic resonance (MR)-fusion biopsy 12 mo later. Tissue change was quantified intraoperatively by measuring the backscatter of ultrasound waves during ablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Gleason grade group (GG) ≥2 cancer on postablation biopsy was the primary outcome. Secondary outcomes included GG ≥1 cancer, Prostate Imaging Reporting and Data System (PI-RADS) scores ≥3, and evidence of tissue destruction on post-treatment magnetic resonance imaging (MRI). A Student's t - test analysis was performed to evaluate the mean TCM scores and efficacy of ablation measured by histopathology. Multivariate logistic regression was also performed to identify the odds of residual cancer for each unit increase in the TCM score. RESULTS AND LIMITATIONS: A lower mean TCM score within the region of the tumor (0.70 vs 0.97, p = 0.02) was associated with the presence of persistent GG ≥2 cancer after HIFU treatment. Adjusting for initial prostate-specific antigen, PI-RADS score, Gleason GG, positive cores, and age, each incremental increase of TCM was associated with an 89% reduction in the odds (odds ratio: 0.11, confidence interval: 0.01-0.97) of having residual GG ≥2 cancer on postablation biopsy. Men with higher mean TCM scores (0.99 vs 0.72, p = 0.02) at the time of treatment were less likely to have abnormal MRI (PI-RADS ≥3) at 12 mo postoperatively. Cases with high TCM scores also had greater tissue destruction measured on MRI and fewer visible lesions on postablation MRI. CONCLUSIONS: Tissue change measured using TCM values during focal HIFU of the prostate was associated with histopathology and radiological outcomes 12 mo after the procedure. PATIENT SUMMARY: In this report, we looked at how well ultrasound changes of the prostate during focal high-intensity focused ultrasound (HIFU) therapy for the treatment of prostate cancer predict patient outcomes. We found that greater tissue change measured by the HIFU device was associated with less residual cancer at 1 yr. This tool should be used to ensure optimal ablation of the cancer and may improve focal therapy outcomes in the future.

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer.

Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20%-65% of highly suspicious lesions on mpMRI (PI-RADS [Prostate Imaging-Reporting and Data System] 4 or 5) are false-positives (FPs), while 5%-10% of clinically significant PC (csPC) are missed. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPRs) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0 ± 7.1 y, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI results or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 min. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. The SUVmax of suspected PC lesions was collected and compared with gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8 ± 6.0 (range, 1.5-25.5) ng/mL and 0.20 ± 0.18 (range, 0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PCs in 8 participants: 7 were csPC and 7 were nonclinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true-positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients versus 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49 ± 4.14 vs. 4.05 ± 1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High-Intensity Focused Ultrasound Therapy.

Focal therapy for localized prostate cancer (PC) using high-intensity focused ultrasound (HIFU) is gaining in popularity as it is noninvasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess the accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 y old (range, 48-78 y), with newly diagnosed PC were prospectively enrolled. Before HIFU, the patients underwent prostate biopsy, multiparametric MRI, 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 mo after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). The SUVmax and SUVpeak of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers, of which 14 were clinically significant (Gleason score ≥ 3 + 4). Multiparametric MRI identified 18 lesions; 14 of them were at least score 4 in the Prostate Imaging-Reporting and Data System. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients, and 5 were incongruent in 5 patients. Before HIFU, 68Ga-PSMA11 identified all target tumors, whereas 68Ga-RM2 PET/MRI missed 2 tumors. After HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in 1 patient. Three significant ipsilateral recurrent lesions were identified, whereas 1 was missed by 68Ga-PSMA11. The pretreatment level of prostate-specific antigen decreased significantly after HIFU, by 66%. Concordantly, the pretreatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: This pilot study showed that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86% of cases, respectively, and accurately verified response to treatment. PET may be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

Changes in the Cerebello-Thalamo-Cortical Network After Magnetic Resonance-Guided Focused Ultrasound Thalamotomy.

Objective: In recent years, transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor (ET). So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in ET patients treated with tcMRgFUS thalamotomy. Methods: Eleven patients diagnosed with ET were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3 Tesla magnetic resonance imaging (3T MRI) including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed before the procedure as well as 1 year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus, and the corticospinal tract in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results: The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p < 0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r = -0.54, p = 0.04; MD: r = 0.57, p = 0.04); RD: r = 0.67, p = 0.036). Further, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r = 0.58; p = 0.062; MD: r = -0.52, p = 0.64; RD: r = -0.61 p = 0.090). Conclusions: Microstructural changes were detected within the CTCT after tcMRgFUS, and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism, and ultimately to improve targeting prospectively. Impact statement The results of this study demonstrate microstructural changes within the cerebello-thalamo-cortical pathways 1 year after MR-guided focused ultrasound thalamotomy. Even more, microstructural changes within the cerebello-thalamo-cortical pathways correlated significantly with clinical outcome. These findings do not only highly emphasize the need of new targeting strategies for MR-guided focused ultrasound thalamotomy but also help to elucidate the treatment mechanism of it.

A review of artificial intelligence in prostate cancer detection on imaging.

A multitude of studies have explored the role of artificial intelligence (AI) in providing diagnostic support to radiologists, pathologists, and urologists in prostate cancer detection, risk-stratification, and management. This review provides a comprehensive overview of relevant literature regarding the use of AI models in (1) detecting prostate cancer on radiology images (magnetic resonance and ultrasound imaging), (2) detecting prostate cancer on histopathology images of prostate biopsy tissue, and (3) assisting in supporting tasks for prostate cancer detection (prostate gland segmentation, MRI-histopathology registration, MRI-ultrasound registration). We discuss both the potential of these AI models to assist in the clinical workflow of prostate cancer diagnosis, as well as the current limitations including variability in training data sets, algorithms, and evaluation criteria. We also discuss ongoing challenges and what is needed to bridge the gap between academic research on AI for prostate cancer and commercial solutions that improve routine clinical care.

Evaluation of post-ablation mpMRI as a predictor of residual prostate cancer after focal high intensity focused ultrasound (HIFU) ablation.

PURPOSE: To evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and PSA testing in follow-up after high intensity focused ultrasound (HIFU) focal therapy for localized prostate cancer. METHODS: A total of 73 men with localized prostate cancer were prospectively enrolled and underwent focal HIFU followed by per-protocol PSA and mpMRI with systematic plus targeted biopsies at 12 months after treatment. We evaluated the association between post-treatment mpMRI and PSA with disease persistence on the post-ablation biopsy. We also assessed post-treatment functional and oncological outcomes. RESULTS: Median age was 69 years (Interquartile Range (IQR): 66-74) and median PSA was 6.9 ng/dL (IQR: 5.3-9.9). Of 19 men with persistent GG ≥ 2 disease, 58% (11 men) had no visible lesions on MRI. In the 14 men with PIRADS 4 or 5 lesions, 7 (50%) had either no cancer or GG 1 cancer at biopsy. Men with false negative mpMRI findings had higher PSA density (0.16 vs. 0.07 ng/mL2, P = 0.01). No change occurred in the mean Sexual Health Inventory for Men (SHIM) survey scores (17.0 at baseline vs. 17.7 post-treatment, P = 0.75) or International Prostate Symptom Score (IPSS) (8.1 at baseline vs. 7.7 at 24 months, P = 0.81) after treatment. CONCLUSIONS: Persistent GG ≥ 2 cancer may occur after focal HIFU. mpMRI alone without confirmatory biopsy may be insufficient to rule out residual cancer, especially in patients with higher PSA density. Our study also validates previously published studies demonstrating preservation of urinary and sexual function after HIFU treatment.