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Ethical approval: The research related to human use complies with all the relevant national regulations, institutional policies and was performed in accordance with the tenets of the Helsinki Declaration and has been approved by the authors’ institutional review board or equivalent committee.; International audience; Deep brain stimulation is widely used to alleviate symptoms of movement disorders. During intraoperative stimulation the influence of active or passive movements on the neuronal activity is often evaluated but the evaluation remains mostly subjective. The objective of this paper is to investigate the potential of a previously developed Weightedfrequency Fourier Linear combiner and Kalman filter-based algorithm to identify tremor types and to isolate the tremorous part. The method is applied to ten intraoperatively acquired accelerometer recordings from eight patients from which 186 phases were manually annotated into: rest, postural and kinetic phase without tremor, and rest, postural and kinetic phase with tremor. The overall accuracy for tremorous phases only is 89.1% and 76.3% when also non-tremorous phases are considered. Two main misclassification cases are identified and further discussed. The results demonstrate the potential of the developed algorithm for the use as an online tremorous movement classifier based on the acquired digital biomarkers.

Poster; International audience; Background: In the past three decades, over 100,000 movement disorder patients like Parkinson’s disease (PD) have been treated by deep brain stimulation (DBS). Despite an increasing use of DBS, the fundamental mechanisms underlying therapeutic and adverse effects as well as the optimal stimulation site remain largely unknown. Among other techniques, computational simulations of the distribution of electric entities have been used to analyze long term chronic stimulation results in relation to the anatomy surrounding the stimulating contact. To our knowledge such methods have never been applied to study clinical results obtained during intraoperative stimulation tests. Therapeutic effects of stimulation are in general visually evaluated based on subjective clinical rating scales which are known for their inter- and intra-rater variability. While very few research groups have attempted intraoperative quantitative tremor evaluation, no research group has used computational simulations of the distribution of electrical entities during such stimulation tests. This study presents a method to correlate simulations of the electric field distribution during intraoperative stimulation tests with quantitatively evaluated symptom improvement and patient specific anatomy to get more informationregarding mechanisms of action and in turn optimize DBS target selection.Method: During DBS surgery of 3 essential tremor patient at the University Hospital in Clermont-Ferrand, France, a previously developed accelerometer based quantitative tremor evaluation technique was used [1]. The ventro-intermediate nucleus (VIM) and its anatomic neighbors were manually outlined based on spontaneous MRI contrasts and using a high field (4.7 Tesla) atlas. For each paitient, two parallel trajectories were planned per hemisphere with 7–8 stimulation test positions per trajectory spanning the region of interest. During the intraoperative stimulation tests, accelerometer data were recorded in sync with the stimulation current amplitude. Tremor improvement was postoperatively quantified compared to baseline tremor. For two stimulation amplitudes (low and high improvement) per position the effect of intraoperative stimulation tests in relation to the patient’s anatomy was studied along with the Department of Biomedical Engineering at Linkoping University. A computational model of the intraoperatively used exploration electrode was developed to simulate electric-field isosurface (0.2 V/mm) in the brain for the previously identified stimulation current amplitudes at the different test positions. Due to the large number of simulations, each voxel in theregion of interest may be part of several isosurfaces-each surface depicting one amplitude responsible for one improvement in tremor. To simplify visualization and interpretation, a maximum improvement map was generated, where each voxel was assigned to the isosurface representing the maximum improvement. Anatomical images, delineated structures, trajectories and improvement maps were visualized together in Paraview (Vtk based visualization software). The resulting visualization was evaluated by clinicians.Results: The software allowed 3D visualization as well as orthographic slices parallel to the trajectory. Clinicians confirmed that it enables the identification of the most effective stimulation areas with respect to the anatomy. A visual analysis of the improvement map for all the patients indicate that the highest improvement in tremor is observed when the region inferior, posterior and medial to the VIM is stimulated, i.e. the region where prelemniscal radiations merge with the VIM.Discussion and Conclusion: The proposed concept based on quantitative tremor evaluation, electric field simulations and patient specific anatomical data proposed provides a unique way to visualize a multitude of information in an interactive and adaptable way. The application of the method to 3 patients shows that the region where prelemniscal radiations merge with the VIM may be optimal for reducing tremor. This is also observed by other researchers. By applying this new method on more patients, the analysis of a high amount of intraoperative data might help to elucidate the mechanism of action of DBS.

International audience; Despite an increasing use of deep brain stimulation (DBS) the fundamental mechanisms underlying therapeutic and adverse effects remain largely unknown. The simulations of electric entities are increasingly used to evaluate stimulation effects. To our knowledge, so far no group has considered such simulations combined with a side effect analysis of data obtained during intraoperative test stimulations. The aim of the present paper is to introduce a method allowing patient-specific electric field simulations for stimulation amplitudes inducing side effects during deep brain stimulation surgery. Two female patients presenting essential tremor, both bilaterally implanted in the ventral intermediate nucleus (VIM) region in the Clermont-Ferrand University Hospital were included in the study. Intraoperative test stimulations were performed on central and posterior trajectories in each hemisphere at 8-9 positions per trajectory. At each position in addition to the evaluation of the therapeutic effects, side effects such as pyramidal symptoms and paresthesia without localization indicator or paresthesia with localization indicated by the patient (in the hand or in the fingers) were noted. The anatomical structures such as VIM and its neighbors were preoperatively manually outlined using the iPlan software (Brainlab, Feldkirchen, Germany) according to spontaneous MRI contrasts [1]. The so identified structures were exported via a specifically designed interface (VVLink, Brainlab, Feldkirchen, Germany). Whenever side effects occurred the inducing stimulation amplitude was chosen for electric field simulations. A finite element method [2] was applied to calculate the electric field distribution. Conductivity values were deduced from the patient's T1 weighted MRI. An isofieldlevel of 0.2V/mm was chosen and the points of the isosurface were exported. They were visualized together with the extracted anatomical structures and the trajectories. The different structures present inside the volume defined by the isofield level and their appearance were determined. Combinations of structures always appearing together for a specific side effect were identified. For both patients, 8 electric field simulations were successfully performed. A first analysis showed that pyramidal effects appear when parts of the ventrooral nucleus (VO) and the VIM were present inside the isosurface. The ventrocaudal lateral nucleus (VCL), the ventrocaudal medial nucleus (VCM) and the VIM were among the identified structures in hand paresthesia (

International audience

International audience; Introduction:DBS is a routinely performed surgical procedure for treatment of movement disorders like Essential Tremor (ET). However, the target selection in DBS is not fully optimized. Incomplete knowledge of the mechanisms of action being one of the reasons, we believe, suboptimal usage of information during surgery is another. We have previously demonstrated the use acceleration sensors to quantify changes in patient tremor during deep brain stimulation surgery. In this paper, we would like to analyze the correlation of the acceleration data results with the different deep brain structures. We present in this paper the result from 5 ET patients implanted in the VIM. Methods: A 3 axis acceleration sensor was used to record and quantify changes in the patient's tremor while test stimulations were performed during DBS surgery using the method described previously. During surgery, for every test stimulation position, the maximum change in patient's tremor and the stimulation amplitude at which it was observed subjectively were noted. As the acceleration data was continuously recorded, it was possible, from offline analysis, to find stimulation amplitudes for changes in statistical features equal to those found subjectively. Additionally, the stimulation amplitudes at which acceleration data suggested maximum change in tremor were also identified for every test stimulation position. For the anatomical analysis, the surgical team carefully identified the anatomical location of the electrode and attributed one thalamic sub-structure to it. Based on this information, the change in tremor and its corresponding stimulation amplitude were grouped into respective sub-structures. For the identification of most effective anatomical sub-structures, we checked for higher reduction in tremor at lower amplitude, both for subjective evaluations and acceleration data analysis. This method was applied to acceleration data collected from 5 Essential tremor patients under a clinical study in University Hospital in Clermont-Ferrand France. A total of 107 test stimulations were analyzed. The different sub-structures of the thalamus have been named according to the previously published nomenclature. Results: The 107 different test stimulation positions were found to be distributed in different parts of the thalamus: Intermedio-Lateral (InL, n=20), Ventro-Oral (VO, n=16), VIM (n=37), Ventro-Caudal-Lateral (VCL, n=2), Central-Medial (CM, n=3), Ventro-Caudal-Medial (VCM, n=23) and the PreLemniscal Radiations (PLR n=6). As the number of test stimulations in the VCL, CM and PLR is low, the significance of the results is very low.For the other structures, the effective stimulation amplitudes for the same clinical effect were lower for acceleration data than the subjective ones (p75%) was on average lower in the VO (1.8 mA) and in VCM (1.9 mA) as compared to the VIM (2.5 mA) and in InL (2.5 mA). Conclusion:The use of sensitive acceleration measurements during the surgery introduces a new approach to analyze the effectiveness of stimulation in different target structures. Our results suggest that the VCM is a better target than the VIM. This information should be considered during the planning of the exploration paths to have more contacts in the effective thalamic area. However, the current analysis does not take into considerations stimulation induced side effects. Those influence the final implant position significantly and can alter our conclusion. Also, attributing one stimulation position to just one structure considering it as a point is suboptimal. A better approach would be to simulate the stimulated volume by using electric field simulations. Along with additional analysis of the results with reference to the known mechanisms of actions of DBS they may result in increasing our understanding of DBS efficiency.

International audience; Introduction: Despite an increasing use of deep brain stimulation (DBS), the fundamental mechanisms underlying therapeutic and adverse effects and the optimal stimulation site remain largely unknown. Computer simulations of electric entities such as electric field or current density are increasingly used to try to identify the stimulated volume around implanted DBS electrodes. So far no group has considered simulations for intraoperatively obtained test stimulation data. The aim of the present paper is to propose a methodology allowing an optimal exploitation of test stimulation data and of the clinical outcome quantitatively assessed by acceleration measurements. By performing patient-specific electric field simulations for stimulation amplitudes at different anatomical positions we aim at getting supplementary data about implicated structures and the mechanism of action of DBS. In order to illustrate technical and clinical feasibility, the presented methodology has been applied to one patient. Methods: One patient with essential tremor presenting tremor and bilaterally implanted in the ventro-intermediate nucleus (Vim) has been included in the present study. Vim and its anatomic neighbors were preoperatively manually outlined using the iPlan software (Brainlab, Feldkirchen, Germany) according to spontaneous MRI contrasts. The identified structures were exported via a specifically designed interface based on VVLink (Brainlab, Feldkirchen, Germany) and VTK (VTK 5.2.0, Kitware Inc. Clifton Park USA). During the intervention, intraoperative test stimulations were performed in 8 to 9 positions per trajectory and on four trajectories (two per hemisphere). Tremor was recorded using a 3-axis accelerometer at each stimulation position just before the start of test stimulation (=baseline) and during the tests. Changes in tremor were expressed as percentage improvement compared to baseline. For each stimulation position, two stimulation amplitudes were chosen for electric field simulations, one with no or low clinical improvement and one with high improvement. A finite element method was applied to calculate the electric field distribution. Conductivity values were deducted from the patient's T1 weighted MRI. An isofieldlevel of 0.2V/mm was chosen and the points of the isosurface were exported. Isosurface, extracted anatomical structures and trajectories were visualized together. The percentage and the numberof appearance of each structure inside the isosurface were calculated and respectively noted. The number of appearance identified with the simulation based approach and from the classical approach where only the anatomical position of the center of the measurement electrode is considered, were compared. A correlation analysis was performed between the clinical change and the percentage of the structure covered by the electric field, taking into account the data of all positions. Results: 69 electric field simulations were performed in total for the four trajectories. Structures identified at least once inside the isosurface of the electric field were the intermediolateral (InL), the dorsolateral (DL), the ventrooral (VO), the Vim, the ventrocaudal medial (VCM) and the center median (CM) nucleus. When comparing the numbers of appearance of each structure between the simulation based and the classical approach, the VO and VCM appeared more often and the DL only appeared with the simulation based approach. The highest improvement was obtained when VO, VCM and CM were present inside the stimulated volume. The correlation of the percentage improvement with the percentage of structure included in the isosurface showed that in some structures (VCM, CM, DL, VO) the clinical improvement varied a lot without a significant change in the percentage of structure volume included. In the InL and Vim an increase of structure parts might correlate with an increase in clinical improvement. Conclusion:A workflow and methodology making possible electric filed simulations on manually outlined anatomical structures could be established. This new concept will allow the analysis of a high amount of intraoperative data obtained in a clinicalstudy which might help to elucidate the mechanism of action of DBS. First results seem to confirm published data hypothesizing that the stimulation of other structures than the Vim might be responsible as well for good clinical effects. But the analysis of more data is necessary to draw any final conclusion.

International audience