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Models and Simulations of the Electric Field in Deep Brain Stimulation Comparison of Lead Designs, Operating Modes and Tissue Conductivity

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Models and Simulations of the Electric Field in Deep Brain Stimulation Comparison of Lead Designs, Operating Modes and Tissue Conductivity Linköping Studies in Science and Technology Linköping University Dissertation No. 1945 Models and Simulations of the Electric Field in Deep Brain Stimulation Comparison of Lead Designs, Operating Modes and Tissue Conductivity Fabiola Alonso Department of Biomedical Engineering Linköping University Linköping 2018 Cover: Depiction of the electric field around DBS electrodes and the word brain . The pictograph is contained in an ancient Egyptian Papyrus, transcribed in the Seventeenth Century B.C. The papyrus is a medical treatise with the earliest mention of the brain in human records. MODELS AND SIMULATIONS OF THE ELECTRIC FIELD IN DEEP BRAIN STIMULATION COMPARISON OF LEAD DESIGNS, OPERATING MODES AND TISSUE CONDUCTIVITY Linköping Studies in Science and Technology Dissertation No. 1945 Copyright © 2018 Fabiola Alonso Supervisor: Karin Wårdell Co-supervisors: Simone Hemm Johannes Johansson Department of Biomedical Engineering Linköping University SE-581 85 Linköping, Sweden ISBN 978-91-7685-261-3 ISSN 0345-7524 Printed by LiU-Tryck, Sweden 2018 Todo es puerta, basta la leve presión de un pensamiento… Octavio Paz, Noche en claro Everything is a door, all one needs is the light push of a thought… Translation by Eliot Weinberger ABSTRACT Deep brain stimulation (DBS) is an established surgical therapy for movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). A thin electrode is implanted in a predefined area of the brain with the use of stereotactic neurosurgery. In the last few years new DBS electrodes and systems have been developed with possibilities for using more parameters for control of the stimulation volume. In this thesis, simulations using the finite element method (FEM) have been developed and used for investigation of the electric field (EF) extension around different types of DBS lead designs (symmetric, steering) and stimulation modes (voltage, current). The electrode surrounding was represented either with a homogeneous model or a patient-specific model based on individual preoperative magnetic resonance imaging (MRI). The EF was visualized and compared for different lead designs and operating modes. In Paper I, the EF was quantitatively investigated around two lead designs (3389 and 6148) simulated to operate in voltage and current mode under acute and chronic time points following implantation.Simulations showed a major impact on the EF extension between postoperative time points which may explain the clinical decisions to change the stimulation amplitude weeks after implantation. In Paper II, the simulations were expanded to include two leads having steering function (6180, Surestim1) and patient-specific FEM simulations in the zona incerta. It was found that both the heterogeneity of the tissue and the operating mode, influence the EF distribution and that equivalent contact configurations of the leads result in similar EF. The steering mode presented larger volumes in current mode when using equivalent amplitudes. Simulations comparing DBS and intraoperative stimulation test using a microelectrode recording (MER) system (Paper III), showed that several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution and that the DBS EF volume can cover, but also extend to, other anatomical areas. Paper IV introduces a method for an objective exploitation of intraoperative stimulation test data in order to identify the optimal implant position in the thalamus of the chronic DBS lead. Patient-specific EF simulations were related to the anatomy with the help of brain atlases and the clinical effects which were quantified by accelerometers. The first results indicate that the good clinical effect in ET is due to several structures around the ventral intermediate nucleus of the thalamus. SVENSK SAMMANFATTNING Djup hjärnstimulering (deep brain stimulation, DBS) är en metod för att ta bort symtom från olika rörelsesjukdomar, t.ex. Parkinsons sjukdom och essentiell tremor. En liten elektrod opereras in i ett väl bestämt område i hjärnan med stereotaktisk teknik. Elektroden påverkar nervceller och fungerar då som en ”pacemaker”. Under de senare åren har flera nya typer av DBS-elektroder och system introducerats. I denna avhandling, studeras olika DBS-elektrodkonfigurationer och deras inverkan på det stimulerade området i hjärnan. Finita element metoden (FEM) används för att skapa datormodeller av elektroderna och av den omgivande hjärnvävnadens elektriska egenskaper (konduktivitet). Hjärnmodellerna kan vara homogena och representera grå vävnad eller vara heterogena dvs. patient-specifika. De senare byggs utifrån en persons magnetresonans (MR) bilder genom att ersätta vävnadtypen med dess respektive konduktivitet. Därefter utför simuleringar av det elektriska fältet (EF) runt elektroden. Resultaten visualiseras för en förbestämd isonivå genom att överlagra elektrod och simulerat EF på MR-bilden. Utbredning av EF och dess volym används som mått vid jämförelse. Elektriska fältet kring DBS elektroderna har jämförts med varandra för olika kontaktinställningar, simulationsmoder (ström, spänning) och stimulationsamplituder. Vidare har simuleringar vid olika tidpunkter, akut och kronisk, undersökts. Detta är baserat på att en förändring av vävnadens konduktivitet runt elektroden sker över tid. Jämförelse har också systematisk utförts för en rad olika situationer relaterat till mikroelektrodstimulering, en metod som används vid själva operationen för att söka upp det bästa målområdet där DBS elektroden ska placeras. Vidare har patientspecifika simuleringar kopplats samman med mätning av rörelse och intraoperativ stimulering för att påbörja arbetet med att skapa kartor av vilka områden som ger bäst effekt av stimuleringen. Simuleringarna visar att det är viktigt att ta hänsyn till den individuella hjärnans konduktiva egenskaper, dvs. patientspecifika simuleringar, och att man bör vänta med den slutliga amplitudinställningen ungefär en månad efter det kirurgiska ingreppet, dvs. när vävnadsegenskaperna stabiliserats runt elektroden. DBS- elektroder som kan styra EF visar på större volymer i strömstyrd inställning jämfört med spänningsstyrd. Stora kontaktytor i elektroden spets bör undvikas. Vid användning av intraoperativ teststimulering bör det beaktas att de kroniska DBS EF- volymerna inte alltid är spridda i samma anatomiska områden. Avhandlingen presenterar metoder och resultat i fyra artiklar som har publicerats i internationella vetenskaplig tidskrifter. LIST OF PUBLICATIONS This thesis is based on the following papers which were published with an open access (CC BY) license. The papers are appended at the end of the thesis. I. Alonso, F., Hemm-Ode, S., & Wårdell, K. (2015). Influence on Deep Brain Stimulation from Lead Design, Operating Mode and Tissue Impedance Changes–A Simulation Study. Brain Disorders and Therapy, 4, pp. 1-8. II. Alonso, F., Latorre, M. A., Göransson, N., Zsigmond, P., & Wårdell, K. (2016). Investigation into deep brain stimulation lead designs: a patient-specific simulation study. Brain sciences, 6(3), 39, pp.1-16. III. Alonso, F., Vogel, D., Johansson, J., Wårdell, K., & Hemm, S. (2018). Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—a Simulation Study. Brain sciences, 8(2), 28, pp. 1-15. IV. Hemm, S., Pison, D., Alonso, F., Shah, A., Coste, J., Lemaire, J. J., & Wårdell, K. (2016). Patient-Specific Electric Field Simulations and Acceleration Measurements for Objective Analysis of Intraoperative Stimulation Tests in the Thalamus. Frontiers in human neuroscience, (10), 577, pp. 1-14 RELATED PUBLICATIONS 1. Alonso F, Latorre M, Wårdell K, Comparison of Three Deep Brain Stimulation Lead Designs under Voltage and Current Modes. In: Jaffray D (eds) IFMBE Proceedings Springer, vol 51, pp 1196-1199, 2015 2. Johansson JD, Alonso F, Wårdell K, Modelling Details for Electric Field Simulations of Deep Brain Stimulation. In: Lhotska L, Sukupova L, Lacković I, Ibbott G (eds). IFMBE Proceedings, Springer, pp 645-648, vol 68/1, 2018 3. Shah AA, Alonso F, Vogel D, Wårdell K, Coste J, Lemaire JJ, Pison D and Hemm S, Analysis of Adverse Effects of Stimulation During DBS Surgery by Patient-Specific FEM Simulations, Proceedings of IEEE EMBC USA, pp 1-5, 2018, Accepted 4. Johansson D, Alonso F, Wårdell K, Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA, In Manuscript 2018 ABBREVIATIONS CC Coverage coefficient CNS Central Nervous System CSF Cerebrospinal fluid CT Computer tomography cZi Caudal part of the zona incerta DBS Deep brain stimulation DC Sørensen-Dice coefficient EF Electric field ET Essential tremor FEM Finite element method FF Fields of Forel FP Floating potential GND Ground GPi Globus pallidus internus IPG Implantable pulse generator MER Microelectrode recording MRI Magnetic resonance imaging OCD Obsessive compulsive disorder PES Perielectrode space PD Parkinson’s disease PDE Partial differential equation PSA Posterior subthalamic area ROI Region of interest SNc Substantia nigra pars compacta SNr Substantia nigra pars reticulata STN Subthalamic nucleus VIM Ventro intermediate nucleous VTA Volume of tissue activated Zi Zona incerta Contents 1 INTRODUCTION ........................................................................................................................ 1 2 NEUROPHYSIOLOGY AND NEUROLOGICAL DISEASES ............................................................ 3 2.1 SIGNALLING UNIT OF THE NERVOUS SYSTEM ................................................................
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