Biomedical Engineering Reference
In-Depth Information
3. Iron oxide nanoparticles have been shown to form stable
deposits in treated tissue (Johannsen et al. 2010), provid-
ing the capability for repeated, cyclic treatments after a
single administration.
magnetic fields will induce eddy current losses in any conductive
medium, and this limits usable fields for biological applications.
Treatments utilizing magnetic nanoparticles attempt to minimize
this field-tissue interaction while maximizing interactions between
the field and the energy-absorbing nanoparticle deposits. Energy
conversion in the particles occurs through hysteresis losses in mul-
tidomain particles or through relaxation losses (Brownian and
Néelian) in superparamagnetic, single-domain particles. Domain
and superparamagnetic behavior is determined by the magnetic
material and particle size, with the latter mode generally appearing
below about 20 nm (for iron oxide). Heating efficiency is mainly
determined by the magnetic material properties, applied field
parameters, and the nanoparticle size distribution. The following
discussion will describe these physical mechanisms in detail.
The dominant physical mechanisms behind heating in macroscale
thermoseeds and magnetic nanoparticles differ and have been widely
discussed in literature (Jordan 2009; Hergt et al. 2002; Hergt et al.
2004; Hergt et al. 2005; Hergt, Dutz, and Röder 2008; Popplewell,
Rosensweig, and Johnston 2002; Rosensweig 2002; Barry 2008; Jones
et al. 1992; Moroz, Jones, and Gray 2002). Thermoseeds mainly take
advantage of resistive heating induced by eddy currents, whereas
heating in magnetic nanoparticles occurs through hysteresis or super-
paramagnetic relaxation mechanisms. Early investigation demon-
strated that nanoscale, superparamagnetic particles were superior to
microscale, multi-domain particles in terms of specific absorption rate
(SAR) due to these varying mechanisms (Jordan et al. 1993; Jordan
2009). This relaxation-based heating shows strong dependence on
applied field strength and frequency, nanoparticle magnetic proper-
ties, and nanoparticle size distribution. The dependence on nanopar-
ticle properties and size highlights the importance of well-controlled
methods of synthesis. Wet-phase chemistry approaches, including
coprecipitation and thermal decomposition, are the most common
methods, generally producing colloidal iron oxide (magnetite-Fe
3
O
4
and maghemite-Fe
2
O
3
) particles, but multifunctional core-shell struc-
tures and surface functionalized particles (with drugs, isotopes, and
biologics) are currently an area of heavy research (Lu, Salabas, and
Schüth 2007; Gupta and Gupta 2005; Krishnan 2010).
A number of different groups have demonstrated the efficacy of
magnetic nanoparticle-based heating in vivo, utilizing a variety of
nanoparticles, field applicators, field parameters, and thermom-
etry methods (Gilchrist et al. 1957; Medal et al. 1959; Chan et al.
1993; Gordon, Hines, and Gordon 1979; Lerch and Pizzarello 1986;
Rand, Snow, and Brown 1981a; Sato et al. 1990; Mitsumori et al.
1994; Luderer et al. 1983; Borrelli, Luderer, and Panzarino 1984).
This extensive preclinical work led to the initiation of several clini-
cal studies utilizing interstitially injected aminosilane-coated mag-
netite nanoparticles activated under a specially designed clinical
field applicator. The results of the most advanced clinical studies,
utilizing thermal therapy in combination with conventional irra-
diation, have demonstrated a clear clinical benefit in terms of sur-
vival for recurrent glioblastoma multiforme patients. Despite these
promising initial indications, research continues in an attempt to
(1) improve the efficiency of heat generation, reducing the required
dosages, (2) optimize the field delivery to better focus energy
deposition (Wust et al. 2006), and (3) develop biological targeting,
allowing for systemic delivery and a truly noninvasive procedure
(Stelter et al. 2009; Hoopes et al. 2009).
17.2.2 Effects of aC Magnetic Fields in
Human application: Calculations
and Clinical Experience
Many forms of electromagnetic radiation exhibit strong interac-
tions with tissue, and this allows direct application in thermal
therapies, such as microwave, RF, and laser ablation. However,
all these modalities exhibit significant attenuation in surface lay-
ers, complicating potential treatment of deep-seated tissues. In
contrast, alternating magnetic fields with frequencies up to 10
MHz have demonstrated essentially no attenuation in tissue
equivalents with radii equal to that of a human torso (Young,
Wang, and Brezovich 2007), offering a platform for uniformly
penetrating deep tissue areas.
The components of human tissue are largely diamagnetic and,
in general, magnetic effects are negligible. However, application of
an alternating electromagnetic induction field will produce eddy
currents in any conducting media, including biological tissue
(Atkinson, Brezovich, and Chakraborty 2007), and like all cur-
rents, are subject to losses. These eddy currents increase radially,
so in the human body, maximum losses will be expected in regions
with the greatest cross-sectional area (such as the torso). Assuming
a uniform field and treating the torso as a cylinder, the volumetric
power generation (
P
) can be estimated by integrating the time-
averaged current density over the cross-sectional area, giving:
22
P
=σ πµ
(
f Hr
a
)
(17.1)
0
where σ is the bulk tissue conductivity, μ
0
is the permeability
of free space,
f
is the applied frequency,
H
a
is the applied field
strength, and
r
is the effective torso radius. The eddy current
losses demonstrate three quadratic dependencies, with frequency,
field strength, and radius. Thus, losses will increase significantly
with increases in field strength, and frequency and will be most
prominent near the exterior of large cross-sections of tissue.
Atkinson et al. performed a series of clinical studies to deter-
mine the range of tolerable parameters for alternating magnetic
field-based treatments (Atkinson, Brezovich, and Chakraborty
2007). Results indicated that field tolerance could be roughly esti-
mated as a limit to the product of frequency and field strength,
17.2 Scientific Background
17.2.1 physical principles
Although magnetic fields demonstrate minimal tissue interactions
compared to other forms of electromagnetic radiation, alternating
