Objective To test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. Methods Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. Results Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. Conclusions Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. Clinicaltrials.gov identifier NCT01827904. Classification of evidence This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.
OBJECTIVE: Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.METHODS: In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.RESULTS: Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.CONCLUSIONS: MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.
Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60–90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ 2, and Cochran’s Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias. The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ 2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1–64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76–86). HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.
The localization of extraprostatic extension (EPE), i.e., local spread of prostate cancer beyond the prostate capsular boundary, is important for risk stratification and surgical planning. However, the sensitivity of EPE detection by radiologists on MRI is low (57% on average). In this paper, we propose a method for computational detection of EPE on multiparametric MRI using deep learning. Ground truth labels of cancers and EPE were obtained in 123 patients (38 with EPE) by registering pre-surgical MRI with whole-mount digital histopathology images from radical prostatectomy. Our approach has two stages. First, we trained deep learning models using the MRI as input to generate cancer probability maps both inside and outside the prostate. Second, we built an image post-processing pipeline that generates predictions for EPE location based on the cancer probability maps and clinical knowledge. We used five-fold cross-validation to train our approach using data from 74 patients and tested it using data from an independent set of 49 patients. We compared two deep learning models for cancer detection: (i) UNet and (ii) the Correlated Signature Network for Indolent and Aggressive prostate cancer detection (CorrSigNIA). The best end-to-end model for EPE detection, which we call EPENet, was based on the CorrSigNIA cancer detection model. EPENet was successful at detecting cancers with extraprostatic extension, achieving a mean area under the receiver operator characteristic curve of at the patient-level. On the test set, EPENet had 80.0% sensitivity and 28.2% specificity at the patient-level compared to 50.0% sensitivity and 76.9% specificity for the radiologists. To account for spatial location of predictions during evaluation, we also computed results at the sextant-level, where the prostate was divided into sextants according to standard systematic 12-core biopsy procedure. At the sextant-level, EPENet achieved mean sensitivity 61.1% and mean specificity 58.3%. Our approach has the potential to provide the location of extraprostatic extension using MRI alone, thus serving as an independent diagnostic aid to radiologists and facilitating treatment planning.
Recent studies have demonstrated the effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of osteoid osteoma (OO), a painful, benign bone tumor. As MRgFUS is a noninvasive and radiation-free treatment, it stands to replace the current standard of care, percutaneous radiofrequency, or laser thermal ablation. Within an institution, creation of a clinical OO MRgFUS treatment program would not only provide cutting edge medical treatment at the current time but would also establish the foundation for an MRgFUS clinical service to introduce treatments currently under development into clinical practice in the future. The purpose of this document is to provide information to facilitate creation of a clinical service for MRgFUS treatment of OO by providing (1) recommendations for the multi-disciplinary management of patients and (2) guidelines regarding current best practices for MRgFUS treatment. This paper will discuss establishment of a multi-disciplinary clinic, patient accrual, inclusion/exclusion criteria, diagnosis, preoperative imaging, patient preparation, anesthesia, treatment planning, targeting and treatment execution, complication avoidance, and patient follow-up to assure safety and effectiveness.