Deep Brain Stimulation: Data Analysis for Clinical Support

DBS Electrode


 

Project summary
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Deep brain stimulation (DBS) is an important therapy for movement disorders such as Parkinson’s disease and essential tremor, and DBS is expanding towards psychiatric illness e.g. Tourette syndrome. In this project we aim at bringing together multiparametric DBS data for clinical support i.e. to go from “mental imagination” to “intuitive visualization” in the surgical planning and follow up of DBS. The work proceeds in parallel but interactive work packages with partners from an international multidisciplinary team with abroad expertise in both technical and clinical DBS-research.

Principle Investigator

Professor Karin Wårdell 
Head of Neuroengineering GroupDept. of Biomedical Engineering (IMT), Linköping University

Investigators

Professor Simone Hemm-Ode 
Institute for Medical Engineering and Medical Informatics, University of Applied Sciences and Art Northwestern Switzerland (FHNW), CH and Guest Researcher at Linköping University.

Dr. Carl-Fredrik Westin 
Director, Lab. of Mathematics in Imaging (LMI), Assoc. Prof. of Radiology, Harvard Medical School, USA and part time visiting Prof. at Linköping University.

Professor Marwan Hariz  
Past chair of Functional Neurosurgery, Institute of Neurology, University College London, UK,  Adjunct Prof. DBS Unit, Norrland Univ. Hospital, Umeå

Dr. Peter Zsigmond 
Consultant Neurosurgeon, Dept. of Neurosurgery, Linköping University Hospital, Sweden

Collaborations

Professor Patric Blomstedt, DBS Unit, Norrland University Hospital, Sweden, Umeå 

Professor Jean-Jacques Lemaire, Dept. of Neurosurgery, Clermont-Ferrand University Hospital, France

Methods

Deep brain stimulation

Deep brain stimulation (DBS) is an important therapy for movement disorders such as Parkinson’s disease and essential tremor, and DBS is expanding towards psychiatric illness e.g. Tourette syndrome (Hariz et al., 2013). Four contacts DBS leads are the most commonly implanted, but DBS leads which can steer the field are other options recently introduced.

Stereotactic DBS implantation and imaging

Stereotactic MRI is used for pre-operative target identification and planning of trajectories. During surgery  the DBS electrode is introduced to the target point and the operation is fulfilled. Intraoperative measurements of neuronal activity with microelectrode recording (MER), microvascular blood flow with laser Doppler flowmetry (LDF), or movement with wrist accelerometers may be done in relation to surgery. Post-operative verification of the DBS lead position is accomplished using MRI or CT (Hemm and Wårdell, 2010).

Patient-specific electric field simulations

Finite element method (FEM) simulation of the electric field surrounding the DBS lead is done in COMSOL Multiphysics. Individual DBS settings together with the pre- and postoperative images makes it patient-specific. Brain models are built in MatLab. Prerpogrammed COMSOL-Apps for DBS lead configurations and stimulations modes will be designed. Results are visualized with the patient own preoperative images (Åström et al., 2009Alonso et al., 2016).

Tractography

By using diffusion MRI (dMRI) different white matter tracts connecting brain regions involved in DBS will be anatomically visualized and combined with the patient-specific electric field simulations. The dentato-rubro-thalamo-cortical circuit is important for DBS in the Vim and Zi (Pujol et al., 2017). Other white fiber tract of interest are the pallidothalamic tracts and the hyperdirect cortico-subthalamic tracts. 

Intraoperative accelerometer measurement of movement

A system for objective intraoperative recording using a 3-axis accelerometer tied to the patient’s (tremor) or neurologist’s (rigidity) is used (Shah et al., 2016). It is combined with intraoperative test stimulations using MER by an analysis method developed in MatLab.
 

Intraoperative optical measurements of blood flow and tissue type

Laser Doppler flowmetry is used for intraoperative measurements of the brain microcirculation and tissue type (Wårdell et al., 2013). A probe with optical fibers is used as guide during creation of the trajectory. The ultimate goal is an online “vessel alarm” for hemorrhage prevention and “bar codes” presenting grey-white tissue boundaries. 

Brain atlas mapping

Anatomical brain atlases created from dissected brains or from MRI (Lemaire et al., 2010) are used for mapping of data. As an example, are the accelerometer values mapped with the clinical rating scales and electric field simulation. (Hemm-Ode et al., 2016).

Data analysis

Data analysis methods for extraction of key parameters (volume of tissue activated, activation distance etc.) that help combine and visualize the multimodal patient-related datasets in a useful, condensed and intuitive way for the user will be developed. 

Demonstrator

A demonstrator will be built in steps. First as separate open access APPs for brain model creation and patient-specific simulations. The final goal is a software demonstrator guiding in presenting individual probabilistic simulation maps of the most likely stimulation regions for various DBS targets/disorders. Physical data gained from intraoperative measurements and clinical scoring will be combined with the simulations and brain maps.

 

Project publications

Thesis

Alonso F, Models and Simulations of the Electric Field in Deep Brain Stimulation: Comparison of Lead Designs, Operating Modes and Tissue ConductivityLinköping Studies in Science and Technology.Dissertation No. 1945, 2018

Latorre M, The Physical Axon: Modeling, Simulation and Electrode EvaluationLinköping Studies in Science and Technology.Dissertation No. 1847, 2017

Papers

Johansson D, Alonso F, Wårdell K,Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA, Accepted, IEEE-EMBC, pp 1-5, 2019

Wårdell K, Hemm-Ode S, Zsigmond P, A System for Combined Laser Doppler Flowmetry and Microelectrode Recording during Deep Brain Stimulation Implantation, Accepted, IEEE-EMBC, pp 1-4, 2019

Latorre M and Wårdell K, A Comparison between Single and Double Cable Neuron Models Applicable to Deep Brain StimulationBiomedical Physics & Engineering Express, 5(2),1-13, 2019


Shah AA, Alonso F, Vogel D, Wårdell K, Coste J, Lemaire JJ, Pison D, Hemm S. Analysis of adverse effects of stimulation during DBS surgery by patient-specific FEM simulations. Conf Proc IEEE Eng Med Biol Soc. 2018 Jul;2018:2222-2225.

 

Johansson JD, Alonso F, Wårdell K, Modelling Details for Electric Field Simulations of Deep Brain Stimulation. In: Lhotska L, Sukupova L, Lackovic I, Ibbott G (eds). IFMBE Proceedings Springer, pp 645-648, vol 68/1, 2018.


Alonso F., Vogel D., Johansson J., Wårdell K, Hemm-Ode S. Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study , Brain Sci., 8(2), 2018

 

Zsigmond P., Hemm-Ode S., Wårdell K. Optical Measurements during Deep Brain Stimulation Lead Implantation: Safety Aspects , Stereotact Funct Neurosurg., 95(6):392-399, 2018

Akbarian-Tefaghi L, Johansson J, Harith A, Eileen J, Limousin P, Zrinzo L, Hariz M, Wårdell K, Foltynie T, Refining the Deep Brain Stimulation target within the Limbic Globus Pallidus internus for Tourette syndrome, Stereotactic and Functional Neurosurgery, Vol. 95, nr 4, pp 251-258, 2017

Hemm S, Pison D, Alonso F, Shah A, Coste J, Lemaire JJ, Wårdell K.
Patient-Specific Electric Field Simulations and Acceleration Measurements for Objective Analysis of Intraoperative Stimulation Tests in the Thalamus. Front Hum Neurosci. 2016 Nov 25;10:577.

Alonso F, Latorre MA, Göransson N, Zsigmond P, Wårdell K. Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study. Brain Sci. 2016 Sep 7;6(3).

Conference presentations
Johansson J, Akbarian-Tefaghi L, Harith A,  Zrinzo L, Limousin P,  Eileen J Hariz M, Wårdell K, Foltynie T, Estimation of effective target area in the globus pallidus during deep brain stimulation for Tourette syndrome. World Society for Stereotactic and Functional Neurosurgery, 17th Quadrennial meeting, Berlin June 26-29, 2017 (Oral)

Wårdell K, Fibre based optical techniques for guidance during stereotactic neurosurgery – a review. World Society for Stereotactic and Functional Neurosurgery, 17thQuadrennial meeting, Berlin June 26-29, 2017 (Oral)

Shah A, Alonso F, Lemaire JJ, Pison D, Coste J, Wårdell K. Schkommodau E, Hemm-Ode SLearning more about the optimal anatomical position for deep brain stimulation in essential tremor patients: 3D visualisation of intraoperative stimulation test results. World Society for Stereotactic and Functional Neurosurgery, 17th Quadrennial meeting, Berlin June 26-29, 2017 (Poster)

Wårdell K, Johansson J, Alonso F, Deep brain stimulation: software for patient-specific electric field simulations, World Society for Stereotactic and Functional Neurosurgery, 17th Quadrennial meeting, Berlin June 26-29, 2017 (Poster)

Alonso F, Vogel D, Wårdell K, Hemm S, Comparison between intraoperative and chronic and deep brain stimulation. World Society for Stereotactic and Functional Neurosurgery, 17th Quadrennial meeting, Berlin June 26-29, 2017 (Poster)

Göransson N, Johansson J, Alonso F, Wårdell K, Zsigmond P, Postoperative lead movement after deep brain stimulation surgery and changes of stimulation area. World Society for Stereotactic and Functional Neurosurgery, 17th Quadrennial meeting, Berlin June 26-29, 2017 (Poster)

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