Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

Cutoff values for the best management strategy for magnetic resonance-guided focused ultrasound ablation for essential tremor.

OBJECTIVE: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. METHODS: Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. RESULTS: Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. CONCLUSIONS: MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ABBREVIATIONS: ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.

Multitier Network Analysis Using Resting-state Functional MRI for Epilepsy Surgery.

Resting-state functional MRI (rs-fMRI) has been utilized to visualize large-scale brain networks. We evaluated the usefulness of multitier network analysis using rs-fMRI in patients with focal epilepsy. Structural and rs-fMRI data were retrospectively evaluated in 20 cases with medically refractory focal epilepsy, who subsequently underwent surgery. First, structural changes were examined using voxel-based morphometry analysis. Second, alterations in large-scale networks were evaluated using dual-regression analysis. Third, changes in cortical hubs were analyzed and the relationship between aberrant hubs and the epileptogenic zone (EZ) was evaluated. Finally, the relationship between the hubs and the default mode network (DMN) was examined using spectral dynamic causal modeling (spDCM). Dual-regression analysis revealed significant decrease in functional connectivity in several networks including DMN in patients, although no structural difference was seen between groups. Aberrant cortical hubs were observed in and around the EZ (EZ hubs) in 85% of the patients, and a strong degree of EZ hubs correlated to good seizure outcomes postoperatively. In spDCM analysis, facilitation was often seen from the EZ hub to the contralateral side, while inhibition was seen from the EZ hub to nodes of the DMN. Some cognition-related networks were impaired in patients with focal epilepsy. The EZ hub appeared in the vicinity of EZ facilitating connections to distant regions in the early phase, which may eventually generate secondary focus, while inhibiting connections to the DMN, which may cause cognitive deterioration. Our results demonstrate pathological network alterations in epilepsy and suggest that earlier surgical intervention may be more effective.

Techniques, Indications, and Outcomes in Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Tremor.

Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is the latest minimally invasive stereotactic procedure, and thalamotomy using this novel modality has demonstrated its effectiveness and safety, especially for patients with essential tremor (ET) and Parkinson's disease (PD). In Japan, the application of MRgFUS to treat ET and PD has recently been covered by health insurance. Technically, the transducer with 1024 elements emits ultrasound beams, which are then focused on the target with a phase control, resulting in optimal ablation by thermal coagulation. The technical advantages of MRgFUS are continuous intraoperative monitoring of clinical symptoms and MR images and fine adjustment of the target by the steering function. Postoperative tremor control is compatible with other modalities, although long-term follow-up is necessary. The adverse effects are usually transient and acceptable. Prognostic factors for good tremor control include high temperature and large lesion size. A high skull density ratio is a factor to achieve high temperature and large lesioning, but it may not be necessary and sufficient for clinical outcomes. For patients with advanced symptoms such as bilateral tremor or head/neck tremor, deep brain stimulation may be recommended because of the adjustability of stimulation and the possibility of bilateral treatment. Patients have high expectations of MRgFUS because of its non-invasiveness. To perform this treatment safely and effectively, physicians need to understand the technological aspects, the physiological principles. To choose the appropriate modality, physicians also should recognize the clinical advantages and disadvantages of MRgFUS compared to other modalities.

[Magnetic Resonance-guided Focused Ultrasound Ablation:Techniques and Neurological Applications].

Magnetic resonance(MR)-guided focused ultrasound ablation(FUS)is a minimally invasive technique for targeted tissue thermo-ablation and is promising for neuromodulation in various neurological disorders. The effectiveness and safety of this technique have been recognized worldwide. In Japan, the applications of FUS for the treatment of essential tremors and Parkinson's disease have recently been covered under health insurance. The FUS system is composed of a phased-array transducer with 1024 elements, with a beam of ultrasound emerging from each element. The phase and amplitude of the beam are computed and controlled to focus on the target with the calculation of computed tomography(CT)profiles, resulting in optimal thermo-ablation. To utilize FUS safely and effectively, a deep understanding of the physics of this technology is necessary. Furthermore, the technique should be compared with other options including deep brain stimulation(DBS)and radiofrequency thermo-ablation. Although FUS has received attention because of minimally invasive characteristics and a possibility of procedural target refinement, DBS has some advantages on bilateral implantation, a potential of postoperative adjustment, and control of head/leg tremors. In this article, we first reviewed the physics of FUS and demonstrated the typical treatment protocols. Second, we reviewed the outcomes from the existing literature, and revealed the advantages and disadvantages of this procedure, with the evaluation of the optimal condition for FUS.

Distributed source analysis of magnetoencephalography using a volume head model combined with statistical methods improves focus diagnosis in epilepsy surgery.

Deep-seated epileptic focus estimation using magnetoencephalography is challenging because of its low signal-to-noise ratio and the ambiguity of current sources estimated by interictal epileptiform discharge (IED). We developed a distributed source (DS) analysis method using a volume head model as the source space of the forward model and standardized low-resolution brain electromagnetic tomography combined with statistical methods (permutation tests between IEDs and baselines and false discovery rate between voxels to reduce variation). We aimed to evaluate the efficacy of the combined DS (cDS) analysis in surgical cases. In total, 19 surgical cases with adult and pediatric focal epilepsy were evaluated. Both cDS and equivalent current dipole (ECD) analyses were performed in all cases. The concordance rates of the two methods with surgically identified epileptic foci were calculated and compared with surgical outcomes. Concordance rates from the cDS analysis were significantly higher than those from the ECD analysis (68.4% vs. 26.3%), especially in cases with deep-seated lesions, such as in the interhemispheric, fronto-temporal base, and mesial temporal structures (81.8% vs. 9.1%). Furthermore, the concordance rate correlated well with surgical outcomes. In conclusion, cDS analysis has better diagnostic performance in focal epilepsy, especially with deep-seated epileptic focus, and potentially leads to good surgical outcomes.