Peripheral nerve magnetic stimulation: influence of tissue nonhomogeneity
 Vessela TZ Krasteva^{1},
 Sava P Papazov^{1} and
 Ivan K Daskalov^{1}Email author
DOI: 10.1186/1475925X219
© Krasteva et al; licensee BioMed Central Ltd. 2003
Received: 25 September 2003
Accepted: 23 December 2003
Published: 23 December 2003
Abstract
Background
Peripheral nerves are situated in a highly nonhomogeneous environment, including muscles, bones, blood vessels, etc. Timevarying magnetic field stimulation of the median and ulnar nerves in the carpal region is studied, with special consideration of the influence of nonhomogeneities.
Methods
A detailed threedimensional finite element model (FEM) of the anatomy of the wrist region was built to assess the induced currents distribution by external magnetic stimulation. The electromagnetic field distribution in the nonhomogeneous domain was defined as an internal Dirichlet problem using the finite element method. The boundary conditions were obtained by analysis of the vector potential field excited by external currentdriven coils.
Results
The results include evaluation and graphical representation of the induced current field distribution at various stimulation coil positions. Comparative study for the real nonhomogeneous structure with anisotropic conductivities of the tissues and a mock homogeneous media is also presented. The possibility of achieving selective stimulation of either of the two nerves is assessed.
Conclusion
The model developed could be useful in theoretical prediction of the current distribution in the nerves during diagnostic stimulation and therapeutic procedures involving electromagnetic excitation. The errors in applying homogeneous domain modeling rather than real nonhomogeneous biological structures are demonstrated. The practical implications of the applied approach are valid for any arbitrary weakly conductive medium.
Background
The analysis of electrical fields induced by magnetic stimulation has been addressed by many authors. However, possible domain nonhomogeneity, nonlinearity, or anisotropy usually have not been considered, even in relatively recent works [1–5]. However, some studies have to some extent taken into account media characteristics [6–9], and Miranda et al. [10] did consider nonhomogeneity in brain tissue layers. Nonhomogeneities do influence correct coil design, excitation current, and positioning with respect to stimulation sites.
It is well known that excitation of peripheral nerves is achieved by electrical current or magnetically induced current, especially by the component parallel to the nerve, as ensuing from the wellknown cable equation [1]:
where V _{ m }, τ, λ, are, respectively, the transmembrane potential, the membrane timeconstant, and the fiber length constant.
With magnetic stimulation, the Jz component, only a fraction of the globally induced current field pattern, is associated with the properties of the conductive medium. The induced current density (J) distribution depends on the electric field, but also on the tissue specific resistivities. Excitation will occur at sites where the local current density exceeds a certain threshold.
When diagnosing, for example, nerve compression in the carpal canal by using magnetic stimulation, one difficulty is the need for separate excitation of the median and ulnar nerves. The electromyogram examination for diagnosis of nerve compression in the carpal canal is done routinely by electrical stimulation of n. medianus over the wrist, and recording the evoked potential from the 3^{rd} finger (the 4^{th} finger is also partly innervated by n. medianus). More proximal stimulation is not recommended, especially for the diagnosis of carpal tunnel syndrome, as other injury may be present along the nerve.
The problem of separate electrical stimulation of n. medianus and n. ulnaris is especially complicated in babies and small children, due not only to the small size of the member, but also to the intensive pain involved.
From a biomedical engineering point of view, the problem is related to the induced electrical field and the resulting current density distribution analysis in nonhomogeneous and anisotropic biological structures.
The above considerations defined our main study objectives :

to show and assess the differences between induced fields and current density with and without accounting for nonhomogeneity, using an adequate model of the stimulated object;

to assess the possibility of selective median and ulnar nerve stimulation in the wrist region.
Methods
In addition, this study involved the use of MATLAB 5.2 (MathWorks, Inc., Natick, USA), Mathematica 4.0 (Wolfram Research, Inc., Champaign, USA) and several inhouse developed linking modules.
 a)
homogeneous structure of specific resistivity ρ = 5 Ωm; the value was chosen as a very approximate average of the conductivity of nerves.
 b)
nonhomogeneous structure that takes into account the anisotropy of the nerves and the muscles. The specific resistivities were chosen to correspond to the regions marked in Fig. 2, as follows [e.g. [6, 11]]:
M _{ 1 } – connective tissue, buffer zone between various tissues  ρ_{1} = 10 Ωm;
M _{ 2 } – tendons  ρ_{2} = 5 Ωm;
M _{ 3 } – extracellular space  ρ_{3} = 6 Ωm;
M _{ 4 } – blood vessels  ρ_{4} = 2.5 Ωm;
M _{ 5 } – nerves  ρ_{5x }= ρ_{5y }= 10 Ωm ; ρ_{5z }= 1 Ωm;
M _{ 6 } – bone  ρ_{6} = 160 Ωm;
M _{ 7 } – cartilage  ρ_{7} = 40 Ωm;
M _{ 8 } – skin and fat  ρ_{8} = 20 Ωm;
M _{ 9 } – articular disc  ρ_{9} = 60 Ωm;
M _{ 10 } – muscles  ρ_{10x }= ρ_{10y }= 13.2 Ωm; ρ_{10z }= 1.9 Ωm;
The medium was taken to be magnetically homogeneous, with relative magnetic permeability μ_{ r }= 1 assigned to all subregions.
The external magnetic field was excited by five identical squareshaped coils (1 cm side) in fanlike configuration (slinky coils [8]), positioned 5 mm above the skin (due to the need for adequate coil isolation). The 1 cm active coil length was chosen taking into account the model length, limited to ± 2 cm, and also the fact that although of small size, such coils can be manufactured.
The excitation currents for the coils were generated by RLCcontour capacitor discharge (R = 1.75 Ω, L = 5.146 μH, C = 32 μF), with I = 1000A (peak current). The initial current slope (di(t) / dt)_{ t=0}was assessed to be 10^{7} A/s, at f = 10 kHz approximate equivalent frequency in stationary sinusoidal mode. The influence of skin, proximity and twisting effects [12] were not considered in the computations for R and L.
Two coil positions were studied (Fig. 2): (A) for stimulation of the median nerve, and (B) for stimulation of the ulnar nerve. The same type of coordinate system was used for each of the coil positions: Zaxis along the quasicylindrical surface generatrix (i.e. parallel to the nerves), Yaxis perpendicular to the surface, and Xaxis tangent to the surface. Z = 0 was selected at the center of the common part of the coils.
The coil disposition (Fig. 2) with respect to the two nerves yielded the following distances (from the center of the active conductor to the center of the respective nerve): from coil A to the median nerve 13,5 mm and to the ulnar nerve 40 mm; from coil B to the median nerve 38 mm and to the ulnar nerve 18,3 mm.
The analysis of the induced eddy fields in the nonhomogeneous domain was performed according to a previously developed approach [9]. Its main points are:
a) Defining the field of the external electromagnetic source by the equation for the magnetic vector potential of a current contour [e.g. [13]]:
For a number of n coils, each of w windings, and currents i _{ k }(t), k = 1,2,...,n, the following equation was used:
b) Calculation of the three vectorpotential components A _{ x }, A _{ y }and A _{ z }for the nodes which belong to the boundary regions of the examined 3D volume (1900 nodes). These potentials were introduced as Dirichlet boundary conditions.
For magnetically homogeneous media (μ = const), using the Coulomb gauge div = 0 and neglecting the field potential component φ, the homogeneous form of the diffusion equation is obtained:
For sinusoidal harmonic potentials the Helmholtz equation was used:
where σ = 1/ρ is the specific conductivity of the respective region.
The strict solution of the problem for φ ≠ 0 and div = 0, neglecting the current of the electrical induction, requires the use of a system of equation [14, 16]:
In case of nonhomogeneous medium with small differences between specific conductivities, the surface charges ρ_{ s }at the boundaries are neglected [15] and respective φ ≡ 0.
c) The boundary conditions at the interface between different media are obtained automatically by the FEM [15], in connection with the principles of continuity, ensuing from the Maxwell equations.
d) The induced electrical field vector in homogeneous subregions is determined in the FEM by the following relations:
or in the harmonic mode:
The respective current density is:
Results
As was noted in the Background section above, excitation of peripheral nerves is achieved by electrical current or magnetically induced current, especially by the current component parallel to the nerve. The induced current density distribution (Jz) depends on the electric field, but also on the tissue specific resistivities. Excitation will occur at sites where the local current density exceeds a certain threshold.
Current density data (Jz component) in the nerve fibers for the two coil positions, in homogeneous and nonhomogeneous model.
Coil Position  Homogeneity & Isotropy  Median nerve  Ulnar Nerve  Ratio  

[A/m^{2}]  [A/m^{2}]  [A/m^{2}]  [A/m^{2}]  [A/m^{2}]  [A/m^{2}]  
A  Yes  10.45  7.38  3.1  0.66  0.59  0.34  12.5 
A  No  45.00  29.74  11.41  3.98  3.71  2.04  8.01 
B  Yes  0.70  0.62  0.37  2.06  1.74  0.87  2.81 
B  No  3.44  2.95  1.58  7.98  6.35  2.91  2.15 
Discussion
We should note that the image definition (Figs. 4,5,6,7) and the current profiles smoothness (Fig. 8) depend on the finite element mesh size used, which was restricted by the total number of elements in the model and their respective distribution (Fig. 2).
The impact of considering nonhomogeneity and anisotropy in this particular task can be assessed by comparing the respective current density distributions in Figs. 4,5 and Figs. 6,7. The eddy currents in the nonhomogeneous model are concentrated in low resistivity regions under the stimulation coils. Moreover, the maximum eddy current density in the nerves was found to be significantly higher in the case of nonhomogeneous domain – about 4.31 times for the median nerve and 4.91 times for the ulnar nerve (Table 1). The selected average value of the homogeneous domain specific resistivity (ρ = 5 Ωm) is lower than that of the compound structure, where the bone (ρ = 160 Ωm) and other tissues (ρ > 5 Ωm) occupy more than about 33% and 25% of the domain, respectively. The blood vessels, having much lower specific resistivity, cover negligibly smaller portion of the domain.
Another way to present the inadequacy of homogeneous analysis can be seen in the graphs of Fig. 8. As shown above, J _{ z }for the coil position (A) in the nonhomogeneous domain has four to five times higher peak value than in the homogeneous medium. The current density is not exactly proportional to the conductivity because current density distribution is considered – J will depend on conductivity of adjacent structures due to compression or rarefaction of current lines. These results might be useful for future research related to stimuli propagation along the nerve.
In connection with the profiles of Fig. 8, it should be noted that at every node of the boundary surfaces the value of the vectorpotential was obtained from the coil current. The eddy currents induced were defined by solving this boundary problem with dependence of the specific resistivities in each volume element and of the accepted equivalent frequency. Jz is therefore not restricted to a condition Jz = 0 at the boundaries, so that the profiles obtained might be accepted as realistic. Also, the model length of ± 2 cm compared to the 1 cm active coil side seems to be an acceptable compromise.
The possibilities for selective stimulation were assessed. The distances between coils and nerves should be taken into account. As specified in Methods section above, these distances are (Fig. 2): from coil position A to the median nerve 13,5 mm, and to the ulnar nerve 40 mm; from coil position B to the median nerve 38 mm and to the ulnar nerve 18,3 mm.
 1.
The relatively complicated introduction of stimulation coil currents in the basic FEM software module was avoided. A first step involved an analyticalnumerical procedure for obtaining the magnetic vectorpotential of the external field. The necessary computation of the integrals in Eq. (3) does not lead to essential difficulties.
 2.
The solution of the internal Dirichlet problem, after the already available vectorpotential of the external field and its use for defining the boundary conditions, becomes a routine procedure. According to the uniqueness theorem [e.g. [17, 18]], the solution was unique, considering the limited volume. The accepted nonhomogeneity did not infringe on this condition [14, 15]. An indirect verification for respecting the uniqueness conditions, even with the introduced partial anisotropy, was the relatively fast convergence of the procedures related to the FEM application.
 3.
The program allowed solution of the Helmholtz equation, valid for harmonic mode. The solution for harmonic mode could lead to unstable solutions using FEM, even for analysis in linear domains, depending on various factors (e.g. geometry of the region and subregions, type of mesh generator, elements used, etc). The proposed approach yielded stable solutions in all cases.
 4.
A more accurate model would require increasing the domain longitudinal dimension while preserving solution stability. Increasing the length from 4 to 6 cm would raise the number of elements from 114,638 to 180,000. A still more detailed model structure would require more than 600,000 elements.
 5.
The excitation system selected, with five fanlike square coils, was one possible application. Optimization procedures could be used, with appropriate criteria and limiting conditions. The selected coil size is rather small, but it is feasible and consistent with the model (and wrist) dimensions.
 6.
Additional studies may include the cable equation (Eq. 1), in relation to propagation velocities along peripheral nerves, by taking into account nonhomogeneity and anisotropy, for various coil shapes and positions.
 7.
The proposed procedure is applicable, in principle, for electromagnetic stimulation of other excitable structures.
Conclusion
We have presented an application of the induced electrical field approach to magnetic stimulation of peripheral nerves in nonhomogeneous tissues. Solutions of two specific problems were proposed:

assessment of the induced electrical field gradient under conditions of nonhomogeneity and in relation to possible solution of the cable equation;

analysis of the possibilities for selective stimulation.
The method developed is of limited accuracy, but its possible errors should be considered in view of the various random factors appearing in the process of stimulation. The results presented demonstrate that neglecting nonhomogeneity and to some extent anisotropy, could introduce essential and strongly misleading errors.
Declarations
Acknowledgements
The authors thank the Technical University of Sofia for granting use of the FEM software.
Authors’ Affiliations
References
 Basser P, Roth B: New currents in electrical stimulation of excitable tissues. Annu Rev Biomed Eng 2000, 02: 377–397. 10.1146/annurev.bioeng.2.1.377View ArticleGoogle Scholar
 Tofts PS: The distribution of induced current in magnetic stimulation of the nervous system. Phys Med Biol 1990, 35: 1119–1128. 10.1088/00319155/35/8/008View ArticleGoogle Scholar
 Ruohonen J, Ravazzani P, Nilsson J, Panizza M, Grandori F, Tognola G: A volumeconduction analysis of magnetic stimulation of peripheral nerves. IEEE Trans Biomed Eng 1996, 43: 669–678. 10.1109/10.503174View ArticleGoogle Scholar
 Karu PE, Stuchly MA: Quasistatic electric field in a cylindrical volume conductor induced by external coils. IEEE Trans Biomed Eng 1994, 41: 151–158. 10.1109/10.284926View ArticleGoogle Scholar
 Roth BJ, Saypol JM, Hallet M, Cohen LG: A theoretical calculation of the electric field induced by magnetic stimulation of a peripheral nerve. Muscle & Nerve 1994, 13: 734–741.View ArticleGoogle Scholar
 Nagarajan S, Durand M: Analysis of magnetic stimulation of a concentric axon in a nerve bundle. IEEE Trans Biomed Eng 1995, 42: 926–932. 10.1109/10.412659View ArticleGoogle Scholar
 Roth BJ, Saypol JM, Hallet M, Cohen LG: A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroenceph Clin Neurophysiol 1991, 81: 47–56. 10.1016/01685597(91)901035View ArticleGoogle Scholar
 Ragan PM, Wang W, Eisenbrg SR: Magnetically induced currents in the canine Heart: A finite element study. IEEE Trans Biomed Eng 1995, 42: 1110–6. 10.1109/10.469378View ArticleGoogle Scholar
 Krasteva VT, Papazov SP, Daskalov IK: Magnetic Stimulation for nonhomogeneous biological structures. BioMed Eng Online 2002, 1: 3. 10.1186/1475925X13View ArticleGoogle Scholar
 Miranda PC, Hallet M, Basser PJ: The electric field induced in the brain by magnetic stimulation: A 3D Finiteelement analysis of the effect of tissue heterogeneity and anisotropy. IEEE Trans Biomed Eng 2003, 50: 1074–1085. 10.1109/TBME.2003.816079View ArticleGoogle Scholar
 Malmivuo J, Plonsey R: Bioelectromagnetism. Oxford University Press, New YorkOxford 1995.Google Scholar
 Ravazzani P, Ruohonen J, Tognola G, Anfonsso F, Ollikainen M, Ilmoniemi , Grandori F: Frequencyrelated effects in the optimization of coil for magnetic stimulation of nervous system. IEEE Trans Biomed Eng 2002, 49: 463–470. 10.1109/10.995685View ArticleGoogle Scholar
 Panofsky WKH, Phillips M: Classical electricity and Magnetism. AddisonWesley Publishing Company, INC, Cambridge 42, Mass 1964.Google Scholar
 Coulomb JL, Sabonnadiere JC: Cao en Electrotechnique. Hermes ublishing 1985.Google Scholar
 Silvester PP, Ferrari RL: Finite elements for electrical engineers. Cambridge University Press CambridgeLondonNew York 1983.Google Scholar
 Novozhilov YuV, Yappa YuA: Electrodynamics. Mir Publishers, Moscow 1981.Google Scholar
 Jakson JD: Classical Electrodynamics. JW & Sons, NewYorkLondon 1962.Google Scholar
 Stratton JA: Electromagnetic theory. McGGRAWHILL, New York and London 1941.Google Scholar
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