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The use of magnetic nanoparticles in low frequency inductive hyperthermi

Article  in  COMPEL International Journal of Computations and Mathematics in Electrical · July 2012

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3 authors:

Arkadiusz Miaskowski Bartosz Sawicki

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Inductive Hyperthermia

Abstract

Purpose – The paper aims to present the basic ideas of magnetic nanoparticles’ usage in the breast cancer treatment,

which is called magnetic fluid hyperthermia. The proposed approach offers a relatively simple methodology of energy

deposition allowing an adequate temperature control at the target tissue, in our case a cancerous one. By means of a

numerical method the authors investigated two heating effects caused by varying magnetic fields i.e. eddy currents power

density heating effect was compared with magnetic nanoparicles one.

Design/methodology/approach – In order to numerically investigate the combination of the overheating effect of

magnetic nanoparticles and the eddy current one, the Finite Element Method solver based on FEniCS project has been

prepared. To include the magnetic fluid in the model it has been assumed that power losses in the magnetic nanoparticles

are completely converted into heat according to experimentally developed formula. That formula can be interpreted as the

hysteresis losses with regard to the volume of magnetic fluid. Finally, the total power density has been calculated as the

product of the sum of power density from eddy currents and hysteresis losses. That methodology has been applied to

calculate the effectiveness of magnetic fluid hyperthermia with regard to the female breast phantom.

Findings – The paper presents the methodology which can be used in magnetic fluid hyperthermia therapy planning

and Computer Aid Diagnosis (CAD). Furthermore, it is shown how to overcome one of the most serious engineering

challenges connected with hyperthermia i.e. achieving adequate temperature in deep tumors without overheating the

body surface.

Practical implications – The obtained results connected with the assessment of eddy currents effect suggest that

during hyperthermia treatment the configuration which consists of an exciting coil and human body, plays a curial role.

Moreover, the authors believe that these results will help to predict the skin surface overheating that accompanies deep

heating. The presented methodology can be used by engineers in the development of Computer Aid Diagnosis systems.

Originality/value – In a given patient’s situation a number of choices must be made to determine the parameters of

the hyperthermia treatment. These include the need of multiple-point temperature measurements for accurate and

thorough monitoring. Treatment planning will require accurate characterization of the applicator deposition pattern and the
tissue parameters, as well as the numerical techniques to predict the resultant heating pattern. The presented paper

shows how to overcome these problems from the numerical point of view at least.

Keywords Magnetic fluid hyperthermia, Finite Element Method, computer simulation.

Paper type: Research paper

Introduction

Magnetic nanoparticles have attracted much attention because of their important applications in biomedicine. These

applications involve the tagging or labelling of the desired biological entity with magnetic material, and after that,

separating these tagged entities via a fluid-based magnetic separation device (Moldey, 1982, Sangregorio, 1999,

Kularatne, 2002). They have also been used in drug delivery (Senyei, 1978) and MRI contrast enhancement ( Semelka,

2001, Enochs, 1999, Bulte, 1999) and finally, as the cancer or tumor therapy by hyperthermia (Duguet, 2006). Magnetic

fluid hyperthermia, which is the combination of inductive applicator and magnetic fluid (nanoparticles) injected into

cancerous tissue, has also attracted much attention because of their considerable heating effects in time-varying

magnetic field (Figure 1). It can increase the temperature in tumours to 43-48 0C, and therefore leads to apoptosis.

Figure 1 Low frequency hyperthermia idea – the magnetic fluid injected into cancerous tissue and then external

magnetic field was applied.

The Faraday induction law says that if H field is of sinusoidal variation, it induces an internal E field in the tissues (and

eddy currents density J). It should be mentioned that inductive applicators are working in deep heating regime. It means

that the frequency should be high enough to produce a sufficient internal E field but lower than 10 MHz for appropriate

penetration depth of the electromagnetic field. Moreover, for biomedical reasons, the frequency of hyperthermia device

has to be higher than 50 kHz to avoid neuromuscular electrostimulation (Jordan, 2001, Pankhurst, 2003).
 On the other hand, ferromagnetic nanoparticles heating effect is present the cancerous tissue. The generation of heat

by magnetic substances in an external alternating magnetic field may be caused by several physical loss processes as

described in details in Fannin (2002) . In our case we have simplified the heat generation by magnetic nanoparticles to

hysteresis losses like in Yamada (2007) and Miaskowski (2010). This assumption means that the maximum of hysteresis

losses may be expected for single domain iron oxide particles near to a mean diameter of 30 nm (Hergt, 2006). To

validate such a simplified physical model of heat generation phenomenon the experiments have been prepared as

described in details in Miaskowski (2010). During the experiments the authors have investigated the temperature

dependence on the amount of magnetic fluid with regards to the female breast phantom as it is shown in Figure 2. The

authors have concluded that a reasonable assumption is that about 50 mg of magnetic material concentrated in each

cubic centimetre of tumour tissue is appropriate for magnetic hyperthermia in a female breast. Next, to validate the results

obtained from experiments the investigators have developed numerical solver based on Finite Element Method (FEM) as

it is described below.

Figure 2 Elucidation of the experimental set up – 5 turn exciting coil and the phantom.

Background and Methodology

In order to investigate the combination of the overheating effect of magnetic nanoparticles and the eddy current one,

the authors have prepared the FEM solver based on FEniCS project (Logg, 2010) as follows.

Taking into account low conductivity of human tissues and low frequency of electromagnetic field the considered

problem has been divided into a few steps. Firstly, the current density (Jc) in the torus shape coil has been calculated.
 Secondly, describing magnetic field by magnetic vector potential A and knowing that ∇× A = B we have formulated a

partially differential equation (PDE) for magnetic field:

∇ ⋅ ∇ A = − µ 0Jc (1)

Next, using electric scalar potential (ϕ) the eddy current problem in human tissues has been defined as follows:

 ∂A 
∇ ⋅ σ∇ϕ = −∇ ⋅ σ 
 ∂t 

(2)

where σ is the conductivity of tissues. Then current density vector can be expressed as the sum of two components:

dA
J = −σ∇ϕ − σ (3)
dt

Power density (pe) produced by the eddy currents can be written as:

2
J
pe = (4)
σ

To include in our model the magnetic fluid, we have assumed that power losses in the magnetic nanoparticles are

completely converted into heat, which can be expressed by the following formula for heat capacity Q (Yamada, 2007):

W 
Q = km f Dw B 2  ml  (5)

where: km = 2.4×10-3 [W/Hz/(mgFe/ml)/T2/ml], f – exciting frequency of applied field [Hz], B – external magnetic field [T], D w

– weight density of magnetic fluid [mgFe/ml].

Finally, total power density (p tot) is the product of the sum of the power density from the eddy currents and hysteresis

losses, i.e.:

W 
p tot = p e + Q ⋅ 10 6  m3  (6)
 
Numerical Calculations

The methodology described above has been applied to calculate the effectiveness of magnetic fluid hyperthermia with

regard to the female breast phantom. In the phantom we have distinguished three different layers i.e. layer of skin, breast

fat and muscle (equivalent to cancerous tissue) as it is shown in Figure 3. The dimensions of the phantom are shown in

Figure 4.

Figure 3 The model of female breast and its layers.

Figure 4 The dimensions of the phantom.

model and parameters taken from Gabriel (Gabriel, 1996) (see Table 1).

Table 1. Dielectric properties of female breast phantom.

No Layer name Conductivity

[S/m]

1 Skin 0.089

2 Breast fat 0.025

3 Muscle/Tumor 0.370

The weight density of magnetic fluid, Dw=28 mgFe/ml, has been used, which is equivalent to, for example, Resovit

produced by Meito Sangyo Co. from Japan. As the excitation we have used the 5-turn torus coil flowing current with

amplitude of I = 400 A. The coil has been placed about 3 cm above the layer of skin as it is shown in Figure 5.

Figure 5 The complete simulation model consists of the coil and the simplified breast model. Lines of the picture show

magnetic field generated by the coil.

authors have also provided an assessment of effects from electromagnetic field interference with human tissues i.e. low

frequency inductive hyperthermia.

Figure 6 Total power density distribution (ptot).

As it is visible in Figure 6. the total power density (p tot) is completely dominated by Q term which represents magnetic fluid.

Color scale has been chosen to visualize much weaker effects related to eddy currents (p e), but one should be informed

that power density in the area of magnetic fluid is over 40 times higher comparing with the rest of the phantom.
Assessment of Eddy Current Effect

The high values of the heat capacity (Q) in the magnetic fluid area is considered as awaiting to achieve hyperthermia

heating effect. In this part of the paper the authors have investigated maximum field values (the power density and eddy

currents) in the surrounding tissues in order to achieve information about the low inductive heating.

Human tissues do not have special magnetic properties, like magnetic fluids, so only the effects caused by eddy

currents are present as the source of heat. The highest values of the current and power density are observed in the skin

layer which is the closest to the coil. The nature of eddy currents phenomena suggests that the size and distance between

the breast phantom and coil play crucial role in estimating the maximum values of p e.

Figure 7 Different sizes and locations of the phantom: a) the experimental setup, b) phantom closer to the coil, c) wider

phantom.

a)

b)

c)

That is why, three cases have been solved and analyzed (see Figure 7). The first one (Figure 7a) is the original

configuration (coil – phantom) taken from experimental setup (see Figure 2 and Figure 4), as described in details in

Miaskowski (2010), the second one, (Figure 7b) i.e. the breast phantom has been moved 2cm closer to the coil. In the last

case (Figure 7c) it has been decided to change the size of the phantom (without size changing of the magnetic fluid layer).

The importance of the case c) cannot be overestimated, because in real life it is not possible to restrict electromagnetic
interferences only to the female breast. It emerges from this that the case shown in Figure 7c can be understood as the

approximation of the whole trunk exposed to the magnetic field produced by hyperthermia setup coils.

Table 2 Maximum field values for three phantoms from Figure 7.

max(pe) max(Q) max(J)

Case a) 0.1 4.6 93

Case b) 0.12 5.6 100

Case c) 0.72 5.6 245

The maximum values of power densities and eddy currents for those three cases are presented in Table II. It should be

noticed that these values have occurred in the skin layer and they are negligible when compared with Q, which occurred

in the cancer layer. Moving phantom model closer to the coil (case b) leads to 20% the increase of power density caused

by eddy currents (p e) as well as by magnetic fluid effect (Q). The third case is even more interesting, where the phantom’s

width is comparable to the coil diameter i.e. 24 cm. In this case the maximum p e increased six times, from 0.12 to 0.72

[W/cm3]. The authors believe this result has proved that future simulations of low frequency hyperthermia should be

extended to the whole torso.

Also the values of maximum current density in our model are presented in Table II. They have changed from 93 to 245

A/m2. Such levels of the current are significantly high for living tissues. Without any doubts, during the stimulation a patient

will feel skin sensations. But similar overrun is usually accepted in other magnetic field therapeutical techniques, such as

Transcranial Magnetic Stimulation (TMS). During TMS the values of current density in the human brain could reach up to

100 A/m2 (Sawicki, 2005). All results mentioned above suggest that during hyperthermia treatment the configuration: coil

– human has a crucial role. The authors believe that these results will help to predict the overheating of surface that

accompanies deep heating.

Conclusions

Taking into account the parameters of our model we have concluded that power density in the cancer layer is about

1000 times higher with magnetic fluid than without it. That means that eddy currents effects are completely negligible

regarding the heating of the injected magnetic fluid. On the other hand, eddy currents are important when talking about
inductive heating. The maximum power density values in the body are determined by the size of body, and so is the

distance between the applicator and the skin.

Magnetic nanoparticles are promising tools for the minimal invasive elimination of small tumors in the breast with the

use of magnetically induced heating. In our simplified model we have not considered the presence of blood flow and

tissue perfusion, both of which are dominant sources of tissue cooling, and both of which vary actively as the tissue is

heated, but the proposed approach offers a very simple methodology of energy deposition allowing an adequate

temperature control at the target tissue.

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Contact Information

Arkadiusz Miaskowski, Ph.D.

Full mailing address: University of Life Sciences in Lublin, Department of Applied Mathematics and Computer Science,

Akademicka 13, 20-950 Lublin, Poland

Email address: [email protected]

Phone number +48 81 4456840

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