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The Physical Axon: Modeling, Simulation and Electrode Evaluation
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. (MINT)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Electrodes are used in medicine for detection of biological signals and for stimulating tissue, e.g. in deep brain stimulation (DBS). For both applications, an understanding of the functioning of the electrode, and its interface and interaction with the target tissue involved is necessary. To date, there is no standardized method for medical electrode evaluation that allows transferability of acquired data. In this thesis, a physical axon (Paxon) potential generator was developed as a device to facilitate standardized comparisons of different electrodes. The Paxon generates repeatable, tuneable and physiological-like action potentials from a peripheral nerve. It consists of a testbed comprising 40 software controlled 20 μm gold wires embedded in resin, each wire mimicking a node of Ranvier. ECG surface Ag-AgCl electrodes were systematically tested with the Paxon. The results showed small variations in orientation (rotation) and position (relative to axon position) which directly impact the acquired signal. Other electrode types including DBS electrodes can also be evaluated with the Paxon.

A theoretical comparison of a single cable neuronal model with an alternative established double cable neuron model was completed. The output with regards to DBS was implemented to comparing the models. These models were configured to investigate electrode stimulation activity, and in turn to assess the activation distance by DBS for changes in axon diameter (1.5-10 μm), pulse shape (rectangular biphasic and rectangular, triangular and sinus monophasic) and drive strength (1-5 V or mA). As both models present similar activation distances, sensitivity to input shape and computational time, the neuron model selection for DBS could be based on model complexity and axon diameter flexibility. An application of the in-house neuron model for multiple DBS lead designs, in a patient-specific simulation study, was completed. Assessments based on the electric field along multiple sample planes of axons support previous findings that a fixed electric field isolevel is sufficient for assessments of tissue activation distances for a predefined axon diameter and pulse width in DBS.

Abstract [sv]

Elektroder används inom sjukvården, både för att mäta biologiska signaler, t.ex. hjärtats aktivitet med EKG, eller för att stimulera vävnad, t.ex. vid djup hjärnstimulering (DBS). För båda användningsområdena är det viktigt med en grundläggande förståelse av elektrodens interaktion med vävnaden. Det finns ingen standardiserad metod för att utvärdera medicinsk elektroders dataöverföringsfunktion. I den här avhandlingen presenteras en metod för att underlätta elektrodtestning. En hårdvarumodell av ett axon (Paxon) har utvecklats. Paxon kan programmeras för att efterlikna repeterbara aktionspotentialer från en perifer nerv. Längs axonet finns 40 noder, vilka var och en består av en tunn (20 μm) guldtråd inbäddad i harts och därefter kopplad till elektronik. Denna testbädd har använts för att undersöka EKG elektroders egenskaper. EKG elektroderna visade på variationer i orientering och position i relation till Paxon. Detta har en direkt inverkan på den registrerade signalen. Även andra elektrotyper kan testas i Paxon, t.ex. DBS elektroder.

En teoretisk jämförelse mellan två neuronmodeller med olika komplexitet, anpassade för användning vid DBS studier, har utförts. Modellerna konfigurerades för att studera inverkan på aktiveringsavstånd från olika axondiametrar, stimulationspuls och stimulationsstyrka. Då båda modellerna visade likvärdiga aktiveringsavstånd och beräkningstid så förordas den enklare neuronmodellen för DBS simuleringar. En enklare modell kan lättare introduceras i klinisk verksamhet. Simuleringarna stöder tidigare resultat som visat att det elektriska fältet är en bra parameter för presentation av resultat vid simulering av DBS. Metoden exemplifieras vid simulering av aktiveringsavstånd och elektriska fältets utbredning för olika typer av DBS elektroder i en patient-specifik studie.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. , p. 75
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1847
National Category
Medical Laboratory and Measurements Technologies Other Medical Engineering Biomedical Laboratory Science/Technology Computer Systems
Identifiers
URN: urn:nbn:se:liu:diva-138587DOI: 10.3384/diss.diva-138587ISBN: 9789176855294 (print)OAI: oai:DiVA.org:liu-138587DiVA, id: diva2:1111850
Public defence
2017-08-25, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 621-2013-6078Swedish Research Council, 2016-03564Linköpings universitetSwedish Foundation for Strategic Research , BD15-0032Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2017-08-21Bibliographically approved
List of papers
1. A Physical Action Potential Generator: Design, Implementation and Evaluation
Open this publication in new window or tab >>A Physical Action Potential Generator: Design, Implementation and Evaluation
2015 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 9, p. 1-11, article id 371Article in journal (Refereed) Published
Abstract [en]

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon’s action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1 to 40 in incremental steps of 1) and the node drive potential (0 to 2.8V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon’s programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Place, publisher, year, edition, pages
Frontiers Research Foundation, 2015
Keywords
Action potential, biomedical electrode, electronic nerve model, nodes of Ranvier, ulnar nerve
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-121086 (URN)10.3389/fnins.2015.00371 (DOI)
Note

Funding agencies| Linköping University; the Swedish Research Council (Grant No. 621-2013-6078)

At the time for thesis presentation publication was in status: Manuscript

Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2017-12-04Bibliographically approved
2. Describing Measurement Behaviour of a Surface Ag-AgCl Electrode Using the Paxon Test Platform
Open this publication in new window or tab >>Describing Measurement Behaviour of a Surface Ag-AgCl Electrode Using the Paxon Test Platform
2016 (English)In: XIV MEDITERRANEAN CONFERENCE ON MEDICAL AND BIOLOGICAL ENGINEERING AND COMPUTING 2016, SPRINGER , 2016, Vol. 57, p. 442-445Conference paper, Published paper (Refereed)
Abstract [en]

A better understanding of bioelectrodes can be acquired with extended testing, which will lead to better methodology and data quality. Today electrodes are evaluated for intraelectrode differences and performance with a traditional gain-phase method, while using the physical axon action potential generator (Paxon) test platform offers extended test possibilities. The direct gain-phase measurements are useful to extract the transfer function of the electrode, as well as some other base parameters. The Paxon test platform is a complementary method that tests electrodes under conditions that are more realistic, mimicking real measurement situations in comparison to the gain-phase method. The Paxon also allows tests to be performed beyond what the gain-phase methods can measure, for example electrode rotation, which would uncover variations in the symmetry of the electrode. When tested, the symmetry properties of the electrode, where the electrodes are rotated in steps of 90 degrees, resulted in a peak to peak variation in detected amplitude of 5.3 +/- 8.9 mV. Therefore, the Paxon appears to be a feasible test platform for characterizing electrodes beyond the gain-phase tests in a semiautomatic manner.

Place, publisher, year, edition, pages
SPRINGER, 2016
Series
IFMBE Proceedings, ISSN 1680-0737
Keywords
Electrode testing; Characterization; Coupling Parameters; Stability test; Axon potential
National Category
Medical Equipment Engineering
Identifiers
urn:nbn:se:liu:diva-129510 (URN)10.1007/978-3-319-32703-7_86 (DOI)000376283000086 ()978-3-319-32703-7 (ISBN)978-3-319-32701-3 (ISBN)
Conference
14th Mediterranean Conference on Medical and Biological Engineering and Computing (MEDICON)
Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2017-06-19Bibliographically approved
3. Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study
Open this publication in new window or tab >>Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study
Show others...
2016 (English)In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 6, no 3, p. 1-16Article in journal (Refereed) Published
Abstract [en]

New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

Place, publisher, year, edition, pages
MDPI, 2016
Keywords
deep brain stimulation (DBS), steering, patient-specific, electric field, finite element method, neuron model, brain model, zona incerta (ZI), electrode design
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-131863 (URN)10.3390/brainsci6030039 (DOI)27618109 (PubMedID)
Available from: 2016-10-11 Created: 2016-10-11 Last updated: 2018-09-10Bibliographically approved

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