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Highlights: • Non-linear iterative structural normalization method focused on the deep brain. • Multi-modality image data from deep brain stimulation patients. • Comparison of ANTS, FNIRT and DRAMMS for the non-linear registrations using different settings for each. • Evaluation of the registration tools based on the analysis of 58 structures of the deep brain segmented manually by a single expert. • ANTS was identified as the best performing non-linear registration tool., 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.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as essential tremor (ET). Positioning of the DBS lead in the patients 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 Funding Agencies|Swiss National Science FoundationSwiss National Science Foundation (SNSF) [CR3212_153370]; Germaine de Stael program of the Swiss Academy of Engineering Sciences; French Ministry of Health [2011-A00774-37]; Swedish Research CouncilSwedish Research Council [2016-03564]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [BD15-0032]

International audience; 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.

International audience; Despite an increasing use of deep brain stimulation (DBS) the fundamental mechanisms of action remain largely unknown. Simulation of electric entities has previously been proposed for chronic DBS combined with subjective symptom evaluations, but not for intraoperative stimulation tests. The present paper introduces a method for an objective exploitation of intraoperative stimulation test data to identify the optimal implant position of the chronic DBS lead by relating the electric field (EF) simulations to the patient-specific anatomy and the clinical effects quantified by accelerometry. To illustrate the feasibility of this approach, it was applied to five patients with essential tremor bilaterally implanted in the ventral intermediate nucleus (VIM). The VIM and its neighborhood structures were preoperatively outlined in 3D on white matter attenuated inversion recovery MR images. Quantitative intraoperative clinical assessments were performed using accelerometry. EF simulations (n = 272) for intraoperative stimulation test data performed along two trajectories per side were setup using the finite element method for 143 stimulation test positions. The resulting EF isosurface of 0.2 V/mm was superimposed to the outlined anatomical structures. The percentage of volume of each structure's overlap was calculated and related to the corresponding clinical improvement. The proposed concept has been successfully applied to the five patients. For higher clinical improvements, not only the VIM but as well other neighboring structures were covered by the EF isosurfaces. The percentage of the volumes of the VIM, of the nucleus intermediate lateral of the thalamus and the prelemniscal radiations within the prerubral field of Forel increased for clinical improvements higher than 50% compared to improvements lower than 50%. The presented new concept allows a detailed and objective analysis of a high amount of intraoperative data to identify the optimal stimulation target. First results indicate agreement with published data hypothesizing that the stimulation of other structures than the VIM might be responsible for good clinical effects in essential tremor. (Clinical trial reference number: Ref: 2011-A00774-37/AU905)