Physical properties of various MNPs [Maenosono and Saita (2006)]
1. Introduction
Hyperthermia is one of many techniques used in oncology. It uses the physical methods to heat certain organ or tissue delivering an adequate temperature in an appropriate period of time (thermal dose), to the entire tumor volume for achieving optimal therapeutic results. Thermal dose has been identified as one of the most important factors which, influences the efficacy of hyperthermia [Perez and Sapareto (1984)]. Although there are definite prescriptions for temperature (generally
The effectiveness of hyperthermia treatment is related to the temperature achieved during the treatment. An ideal hyperthermia treatment should selectively destroy the tumor cells without damaging the surrounding healthy tissue. [Andrä et al. (1999), Lagendijk (2000), Moroz et al. (2002), Maenosono and Saita (2006), Lin and Liu (2009)]. Therefore, the ability to predict the temperature distribution inside as well as outside the target region as a function of the exposure time, possesses a high degree of importance.
In the past fifteen years, MFH has drawn greater attention due to the potential advantages for cancer hyperthermia therapy. In MFH, a nanofluid containing the MNPs is injected directly into the tumor. An alternating magnetic field is then applied to the target region, and then MNPs generate heat according to Néel relaxation and Brownian rotation losses as localized heat sources [Jordan et al. (1999), Jordan
Two techniques are currently used to deliver the MNPs to the tumor. The first is to deliver particles to the tumor vasculature [Matsuki and Yanada (1994)] through its supplying artery; however, this method is not effective for poorly perfused tumors. Furthermore, for a tumor with an irregular shape, inadequate MNPs distribution may cause under-dosage of heating in the tumor or overheating of the normal tissue. The second approach, is to directly inject MNPs into the extracellular space in the tumors. The MNPs diffuse inside the tissue after injection of nanofluid. If the tumor has an irregular shape, multi-site injection can be exploited to cover the entire target region [Salloum et al. (2008a)].
The nanofluid injection volume as well as infusion flow rate of nanofluid are important factors in dispersion and concentration of the MNPs, within the tissue. A successful MFH treatment is substantially dependent on the MNPs distribution in the tissue [Bagaria and Johnson (2005), Salloum et al. (2008a), Salloum
2. Heat dissipation of MNPs
In MFH, after introducing the MNPs into the tumor (Figure 1), an alternating magnetic field is applied. This causes an increase in the tumor temperature and subsequent tumor regression. The temperature that can be achieved in the tissue strongly depends on the properties of the magnetic material used, the frequency and the strength of the applied magnetic field, duration of application of the magnetic field, and dispersion of the MNPs within the tissue.
2.1. Mechanisms of heat dissipation of MNPs
To turn MNPs into heaters, they are subjected to an oscillating electromagnetic field, where the field’s direction changes cyclically. There are various theories which explain the reasons for the heating of the MNPs when subjected to an oscillating electromagnetic field [Brusentsova
There exist at least four different mechanisms by which magnetic materials can generate heat in an alternating field [Nedelcu (2008)]:
Generation of eddy currents in magnetic particles with size >1μ,
Hysteresis losses in magnetic particles >1μ and multidomain MNPs,
Relaxation losses in ‘superparamagnetic’ single-domain MNPs,
Frictional losses in viscous suspensions.
Relaxation losses in single-domain MNPs fall into two modes: rotational (Brownian) mode and Néel mode. The principle of heat generation due to each individual mode is shown in Figure 2.
In the Néel mode, the magnetic moment originally locked along the crystal easy axis rotates away from that axis towards the external field. The Néel mechanism is analogous to the hysteresis loss in multi-domain MNPs whereby there is an ‘internal friction’ due to the movement of the magnetic moment in an external field that results in heat generation. In the Brownian mode, the whole particle oscillates towards the field with the moment locked along the crystal axis under the effect of a thermal force against a viscous drag in a suspending medium. This mechanism essentially represents the mechanical friction component in a given suspending medium [Nedelcu (2008)].
Power dissipation of MNPs in an alternating magnetic field is expressed as [Rosensweig (2002), Nedelcu (2008)]:
where
where
where the shorter time constant tends to dominate in determining the effective relaxation time for any given size of particle.
where
The equilibrium susceptibility
where
Generally, the practical range of frequency and amplitudes are often described as
2.2. Heating rate of aqueous dispersions of MNPs
Based on the theory mentioned in previous section, Lahonian and Golneshan (2011) calculated the power dissipations for aqueous dispersion of mono-dispersed equiatomic face centred cubic iron-platinum (FCC FePt) MNPs varying the diameter of MNP in adiabatic condition. For comparison, also the power dissipations for magnetite (Fe3O4), and maghemite (γ-Fe2O3 ) have been estimated. In Table 1, physical properties of each magnetic material are shown [Maenosono and Saita (2006)].
In practice, the magnetic anisotropy may considerably vary due to the shape contributions of MNPs. For simplicity, however, the shape effect is not taken into account in the above mentioned model.
It has been pointed out that hysteresis losses are important especially for magnetic single domain particles with high magneto-crystalline anisotropy [Hergt et al. (1998)]. However, the hysteresis losses are not considered, because MNPs are assumed as super-paramagnetic in their study.
Figure 3 shows comparative power dissipation for aqueous mono-dispersions of the various MNPs listed in Table 1, assuming
Figure 4 shows the dependence of power dissipation on induction of applied magnetic field, for fixed
Figures 5, 6 and 7 show the dependence of power dissipation on the frequency (
Material | ||||
FCC FePt | 1140 | 206 | 327 | 15200 |
Magnetite | 446 | 9 | 670 | 5180 |
Maghemite | 414 | 4.7 | 746 | 4600 |
Figures 4 to 7 show that dispersion and concentration of MNPs inside the tissue are important factors in heat dissipation of MNPs and temperature distribution inside the tumor and its surrounding healthy tissue. Also, the effect of concentration of MNPs is comparable with the effects of induction and frequency of the magnetic field on the maximum power dissipation. Therefore, study of the MNPs diffusion and concentration, possesses a high degree of importance.
3 Diffusion of MNPs within the biological tissueThe relationship among the MNPs distribution, the blood perfusion, the infusion flow rate, the injection volume of nanofluid, and the tissue structure are not well understood. It is difficult to devise a treatment protocol that enables the optimum distribution of temperature elevation in the tumor. Hence, it is important to quantify the MNPs distribution and heating pattern following the injection regarding the above mentioned factors [Salloum et al. (2008b)].
Diffusion in isotropic tissues, can be modeled as [Nicholson (2001)]:
where
Therefore an increase in the tortuosity and a decrease in the porosity have significant effects on reducing the effective mass diffusivity.
Experimental study of Salloum et al. (2008a) in a tissue-equivalent agarose gel, showed that the particle concentration was not uniform after the injection and were confined in the vicinity of the injection site. Also the particle deposition was greatly affected by the injection rate and amount. Furthermore, the shape of the distribution tended to be more irregular with higher infusion flow rate.
Due to difficulties in experimental studies, to understand the actual spatial distribution of the MNPs after being injected into the tumor, some numerical simulations have been down.
Diffusion of MNPs inside the tissue was simulated by Golneshan and Lahonian (2011a). A square region with side of
Figure 9 shows the concentration of ferrofluid in the tissue for
Figure 10 shows volume fraction of MNPs in the tissue for different ferrofluid injection volumes,
Figure 11 shows the concentration of ferrofluid in the tissue for
Figure 12 shows the concentration of ferrofluid in the tissue for
4. Diffusion of MNPs in a biological tissue for mono and multi-site injection for irregular tumors
Golneshan and Lahonian (2011a) studied diffusion of MNPs in a biological tissue for irregular tumors. A
They considered multi-site injection as shown in Figure 13d and divided the irregular tumor almost into four equal sections. In each injection site, one fourth the amount of
Figure 15 shows the concentration of ferrofluid in
the injection, the maximum concentration of ferrofluid happens at the injection sites, decreasing rapidly with increasing the distance from the injection sites. At this stage, nearly clear boundaries are seen between diffused ferrofluid for each injection regions. As ferrofluid diffuses more and more, these boundaries are disappeared. Thirty minutes after the injection, the ferrofluid is spread all over the tomour [Golneshan and Lahonian (2011a)].
Comparison between mono-site and multi-site injections in Figures 15 show that diffusion of ferrofluid in the tissue for a multi-site injection is much more uniform and covers all points inside the tumor
5. Conclusion
Results showed and clarified that increasing the magnetic nanofluid injection volume, increases the concentration of MNPs inside the tissue. Also, increasing magnetic nanofluid infusion flow rate increased the concentration of MNPs in the center of the tumor only. For irregular tumors, the effect of multi-site injection was investigated. Results showed that multi-site injection of specific quantity of magnetic nanofluid provided a better distribution of MNPs inside the tumor, in contrast to mono-site injection.
References
- 1.
Andrä W. C. G. D’Ambly R. Hergt I. Hilger W. A. Kaiser 1999 Diffusion of Magnetic Nanoparticles Within a Biological Tissue During Magnetic Fluid Hyperthermia J Magn Magn Mater194 197 203 - 2.
Bagaria H. G. Johnson D. T. 2005 Transient solution to the BHE and optimization for magnetic fluid hyperthermia treatment Int J Hyperther21 1 57 75 - 3.
Bellizzi G. O. M. Bucci 2010 On the optimal choice of the exposure conditions and the nanoparticle features in magnetic nanoparticle hyperthermia Int J Hyperther26 389 403 - 4.
Brusentsova T N, N A Brusentsov, V D Kuznetsov, V N Nikiforov 2005 Synthesis and investigation of magnetic properties of Gd-substituted Mn-Zn ferrite nanoparticles as a potential low-TC agent for magnetic fluid hyperthermia J Magn Magn Mater293 298 302 - 5.
Golneshan A. A. M. Lahonian 2010 Diffusion of magnetic nanoparticles within spherical tissue as a porous media during magnetic fluid hyperthermia using lattice Boltzmann method International Congress on Nanoscience and Nanotechnology9 11 November, shiraz iran. - 6.
Golneshan A. A. M. Lahonian 2011a Diffusion of magnetic nanoparticles in a multi-site injection process within a biological tissue during magnetic fluid hyperthermia using lattice Boltzmann method Mech Res Commun38 425 430 - 7.
Golneshan A. A. M. Lahonian 2011b Effect of heated region on temperature distribution within tissue during magnetic fluid hyperthermia using lattice Boltzmann method Journal of Mechanics in Medicine and Biology11 2 457 469 - 8.
Golneshan A. A. M. Lahonian 2011c The effect of magnetic nanoparticle dispersion on temperature distribution in a spherical tissue in magnetic fluid hyperthermia using the lattice Boltzmann method Int J Hypertherm27 3 266 274 - 9.
Hergt R. W. Andrä C. G. d’Ambly I. Hilger W. A. Kaiser U. Richter-G H. Schmidt 1998 Physical limits of hyperthermia using magnetite fine particles IEEE T Magn5 3745 3754 - 10.
Jo´zefczak A. A. Skumiel 2007 Study of heating effect and acoustic properties of dextran stabilized magnetic fluid J Magn Magn Mater311 193 196 - 11.
Jordan A. R. Scholz K. Maier-Hauff M. Johannsen P. Wust J. Nadobny H. Schirra H. Schmidt S. Deger S. Loening W. Lanksch R. Felix 2001 Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia J Mag Mag Mater225 118 126 - 12.
Jordan A. R. Scholz P. Wust H. Fähling J. Krause W. Wlodarczyk B. Sander T. Vogl R. Felix 1997 Effect of magnetic fluid hyperthermia on C3H mammary carcinoma in vivo Int J Hypertherm13 587 605 - 13.
Jordan A. R. Scholz P. Wust H. Schirra T. Schiestel H. Schmidt R. Felix 1999 Endocytosis of dextran and silan-coated magnetite nanoparticles and the effect of intracellular hyperthermia on human mammary carcinoma cells in vitro J Magn Magn Mater194 185 196 - 14.
Kim D H, D E Nikles, D T Johnson, C S Brazel 2008 Heat generation of aqueously dispersed CoFe2O4 nanoparticles as heating agents for magnetically activated drug delivery and hyperthermia J Magn Magn Mater320 2390 2396 - 15.
Lagendijk J J W 2000 Hyperthermia treatment planning Phys Med Biol 45:R61 R76. - 16.
Lahonian M. A. A. Golneshan 2011 Numerical study of temperature distribution in a spherical tissue in magnetic fluid hyperthermia using lattice Boltzmann method IEEE Trans Nanobio10 4 262 268 - 17.
Lin Ch. T. Liu K. Ch 2009 Estimation for the heating effect of magnetic nanoparticles in perfused tissues Int Commun Heat Mass36 241 244 - 18.
Maenosono S. S. Saita 2006 Theoretical assessment of FePt nanoparticles as heating elements for magnetic hyperthermia IEEE T Magn42 1638 1642 - 19.
Matsuki H. T. Yanada 1994 Temperature sensitive amorphous magnetic flakes for intra-tissue hyperthermia Mat Sci Eng A-Struct 181/A182 1366 1368 - 20.
Moroz P. S. K. Jones B. N. Gray 2002 Magnetically mediated hyperthermia: Current status and future directions Int J Hyperther18 267 284 - 21.
Nedelcu G. 2008 Magnetic nanoparticles impact on tumoural cells in the treatment by magnetic fluid hyperthermia Digest J Nanomat Biost3 3 103 107 - 22.
Nicholson C. 2001 Diffusion and related transport mechanism in brain tissue Rep Prog Phys64 815 884 - 23.
Overgaard J. D. Gonzalez M. C. C. H. Hulshof G. Arcangeli O. Dahl O. Mella S. M. Bentzen 2009 Diffusion of Magnetic Nanoparticles Within a Biological Tissue During Magnetic Fluid Hyperthermia Int J Hyperther25 323 334 - 24.
Pankhurst Q. A. J. Connolly S. K. Jones J. Dobson 2003 Application of magnetic nanoparticles in biomedicine J Phys D Appl Phys 36:R167 R187. - 25.
Perez C A, S A Sapareto 1984 Thermal dose expression in clinical hyperthermia and correlation with tumor response/control1 Cancer Res44 4818 4825 - 26.
Rosensweig R E 2002 Heating magnetic fluid with alternating magnetic field J Magn Magn Mater252 370 374 - 27.
Salloum M. R. H. Ma Weeks D. Zhu L. 2008a Controlling nanoparticle delivery in magnetic nanoparticle hyperthermia for cancer treatment: Experimental study in agarose gel Int J Hyperther24 337 345 - 28.
Salloum M. R. H. Ma Zhu L. 2008b An in-vivo experimental study of temperature elevations in animal tissue during magnetic nanoparticle hyperthermia Int J Hyperther24 589 601 - 29.
Thiesen B. A. Jordan 2008 Clinical applications of magnetic nanoparticles for hyperthermia Int J Hyperther24 467 474