Biomedical Engineering Reference
In-Depth Information
17.5 Clinical application in
Cancer therapy
Pre-operative planning:
Imaging: MRI, CT, and US for 3D imaging of tumor
geometry and location.
17.5.1 Components of a Clinical MFH
thermotherapy System
Planning software: Utilize 3D tumor images to plan
implantation trajectories and deposits.
Following is a description of the components necessary for
successful clinical application of magnetic nanoparticle-
based thermal therapy treatment. Reference is made to the
MagForce NanoTherapy (MagForce Nanotechnology AG,
Berlin, Germany) system, as this is the only clinical magnetic
fluid hyperthermia system in use at this time. However, equiv-
alent or similar system components will be required for any
clinical MFH-based treatment. A high-level treatment flow
chart has been included in Figure 17.11, for illustrative pur-
poses. Imaging is not explicitly described as a discrete system
component in the subsequent discussion, but is an integral tool
utilized throughout the process.
MF implantation:
Imaging: Minimally invasive implantation under CT,
TRUS with fluoroscopy, or stereotactic guidance.
Pre-treatment planning:
Imaging: CT measurement of magnetic
nanoparticle distribution.
Planning software: Estimate treatment
temperature distribution based on nanoparticle
distribution and estimated perfusion.
ermometry: In vivo temperature measurement
to estimate mean perfusion rate.
17.5.1.1 Magnetic Nanoparticles
Heating dependence on magnetic nanoparticle properties and poten-
tial core-shell structures have already been discussed. However, keys
to an effective clinical application include high SAR, high biocom-
patibility (acute and long-term), and stability under physiological
conditions. NanoTherm® ® (MagForce Nanotechnologies AG, Berlin,
Germany) is an aqueous dispersion of 15 nm iron oxide cores coated
with aminosilane, for a total hydrodynamic diameter of 100 nm
(Dudeck et al. 2006). The solution has an iron concentration of
112 mg/ml and is directly injected as a number of 0.5 ml deposits.
Treatment planning:
Field applicator: NanoActivator @ 100 kHz:
Pelvic: 3-5 kA/m
oracic/neck: <10 kA/m
Cranial: 12-15 kA/m
→ Ta rget: 41-43ºC for 60 min
ermometry: Intratumoral temperature
measurement to calculate thermal equivalent
dose.
17.5.1.2 pretreatment planning and
Nanoparticle Imaging
Understanding the physical mechanisms behind magnetic
nanoparticle heating and characterization of their performance
in vitro and in preclinical study has provided an extensive knowl-
edge base for predicting performance in vivo, but convenient
tools are still required to effectively translate this understanding
to the clinical setting. Robust and simple methods are necessary
to help clinicians determine the required nanoparticle loading
and expected treatment efficacy, without involved calculation.
The Pennes bioheat equation is a well-accepted method for
solving biological heat transfer problems (Pennes 1948):
Adjunct therapy: Combined radio- and
chemotherapy before, during, and/or after
thermal treatment.
Follow up:
Imaging: PET or SPECT to monitor tumor progression.
MRI cannot be used due to susceptibility artifacts
caused by enduring nanoparticle deposits.
FIGURE 17.11
Components involved in clinical application of MFH.
dT
dt
ρ
c
=
kT
+
(
ρ
c
)
ω
(
T
−+
Tq
)
(17.17)
cp
pblood
b
a
SAR
side can be set to zero. Perfusion can be estimated from values in
literature or various imaging techniques—MRI (Williams et al.
1992), CT (Eastwood et al. 2002), or US (Schrope and Newhouse
1993)). Calculation and measurement of SAR (see Sections 17.2.3
and 17.3.2) has already been discussed, so a solution for either
nanoparticle density or treatment temperature can be found,
given the other value. This can be accomplished analytically
for simple geometries or with finite element methods in more
realistic cases. This relation then provides a tool for calculating
where ρ and c p are the density and specific heat of the tissue and
blood, T is temperature, T a is the arterial blood temperature, t is
time, k is the tissue thermal conductivity, ω b is blood perfusion,
and q SAR has been added for nanoparticle heat generation (i.e.,
SAR from Equations 17.14 and 17.15). Contributions of meta-
bolic heat generation will be insignificant compared to nanopar-
ticle SAR and has been neglected. This equation is often solved
for the steady-state treatment temperature, in which case the left
 
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