Probabilistic stimulation mapping from intra-operative thalamic deep brain stimulation data in essential tremor.

Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood. Retrospective group analysis of intra-operative data recorded from ET patients implanted in the ventral intermediate nucleus of the thalamus (Vim) is rare. Intra-operative stimulation tests generate rich data and their use in group analysis has not yet been explored.Objective.To implement, evaluate, and apply a group analysis workflow to generate probabilistic stimulation maps (PSMs) using intra-operative stimulation data from ET patients implanted in Vim.Approach.A group-specific anatomical template was constructed based on the magnetic resonance imaging scans of 6 ET patients and 13 PD patients. Intra-operative test data (total:n= 1821) from the 6 ET patients was analyzed: patient-specific electric field simulations together with tremor assessments obtained by a wrist-based acceleration sensor were transferred to this template. Occurrence and weighted mean maps were generated. Voxels associated with symptomatic response were identified through a linear mixed model approach to form a PSM. Improvements predicted by the PSM were compared to those clinically assessed. Finally, the PSM clusters were compared to those obtained in a multicenter study using data from chronic stimulation effects in ET.Main results.Regions responsible for improvement identified on the PSM were in the posterior sub-thalamic area (PSA) and at the border between the Vim and ventro-oral nucleus of the thalamus (VO). The comparison with literature revealed a center-to-center distance of less than 5 mm and an overlap score (Dice) of 0.4 between the significant clusters. Our workflow and intra-operative test data from 6 ET-Vim patients identified effective stimulation areas in PSA and around Vim and VO, affirming existing medical literature.Significance.This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical planning.

Probabilistic maps for deep brain stimulation - Impact of methodological differences.

BACKGROUND: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. OBJECTIVE: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. METHODS: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. RESULTS: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. CONCLUSION: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Deep Brain Stimulation: Emerging Tools for Simulation, Data Analysis, and Visualization.

Deep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.

Towards Tracking of Deep Brain Stimulation Electrodes Using an Integrated Magnetometer.

This paper presents a tracking system using magnetometers, possibly integrable in a deep brain stimulation (DBS) electrode. DBS is a treatment for movement disorders where the position of the implant is of prime importance. Positioning challenges during the surgery could be addressed thanks to a magnetic tracking. The system proposed in this paper, complementary to existing procedures, has been designed to bridge preoperative clinical imaging with DBS surgery, allowing the surgeon to increase his/her control on the implantation trajectory. Here the magnetic source required for tracking consists of three coils, and is experimentally mapped. This mapping has been performed with an in-house three-dimensional magnetic camera. The system demonstrates how magnetometers integrated directly at the tip of a DBS electrode, might improve treatment by monitoring the position during and after the surgery. The three-dimensional operation without line of sight has been demonstrated using a reference obtained with magnetic resonance imaging (MRI) of a simplified brain model. We observed experimentally a mean absolute error of 1.35 mm and an Euclidean error of 3.07 mm. Several areas of improvement to target errors below 1 mm are also discussed.

Anatomical brain structures normalization for deep brain stimulation in movement disorders.

Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient's brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.

Stimulation maps: visualization of results of quantitative intraoperative testing for deep brain stimulation surgery.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as essential tremor (ET). Positioning of the DBS lead in the patient's brain is crucial for effective treatment. Extensive evaluations of improvement and adverse effects of stimulation at different positions for various current amplitudes are performed intraoperatively. However, to choose the optimal position of the lead, the information has to be "mentally" visualized and analyzed. This paper introduces a new technique called "stimulation maps," which summarizes and visualizes the high amount of relevant data with the aim to assist in identifying the optimal DBS lead position. It combines three methods: outlines of the relevant anatomical structures, quantitative symptom evaluation, and patient-specific electric field simulations. Through this combination, each voxel in the stimulation region is assigned one value of symptom improvement, resulting in the division of stimulation region into areas with different improvement levels. This technique was applied retrospectively to five ET patients in the University Hospital in Clermont-Ferrand, France. Apart from identifying the optimal implant position, the resultant nine maps show that the highest improvement region is frequently in the posterior subthalamic area. The results demonstrate the utility of the stimulation maps in identifying the optimal implant position. Graphical abstract.

Analysis of adverse effects of stimulation during DBS surgery by patient-specific FEM simulations.

Deep brain stimulation (DBS) represents today a well-established treatment for movement disorders. Nevertheless the exact mechanism of action of DBS remains incompletely known. During surgery, numerous stimulation tests are frequently performed in order to evaluate therapeutic and adverse effects before choosing the optimal implantation site for the DBS lead. Anatomical structures responsible for the induced adverse effects have been investigated previously, but only based on stimulation data obtained with the implanted DBS lead. The present study introduces a methodology to identify these anatomical structures during intraoperative stimulation tests based on patient-specific electric field simulations and visualization on the patient specific anatomy. The application to 4 patients undergoing DBS surgery and presenting dysarthria, paresthesia or pyramidal effects shows the different anatomical structures, which might be responsible for the adverse effects. Several of the identified structures have been previously described in the literature. To draw any statistically significant conclusions, the methodology has to be applied to further patients. Together with the visualization of the therapeutic effects, this new approach could assist the neurosurgeons in the future in choosing the optimal implant position.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study.

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome.