Biomedical Engineering Reference
In-Depth Information
deposition is attempted by planning trajectories that provide
interdeposit spacing between 8 and 10 mm throughout the tumor
(Thiesen and Jordan 2009). In addition, the software can be used in
conjunction with postimplantation CT nanoparticle concentration
data, to estimate field-dependent temperature distributions in the
tissue, using perfusion estimates based on minimally invasive ther-
mometry. Preliminary experience with these methods and software
has yielded reasonable agreement of intratumoral temperatures,
but considerable deviations are found outside of the tumor.
promise in preferential deposition of nanoparticles for treatment
of liver carcinoma (Dudeck et al. 2006), which would offer major
advantages over minimally invasive methods. This procedure will
be discussed in more detail in Section 17.5.2.5.
Nanoparticle retention is another critical factor for successful
implantation. Significant diffusion from the injection site can
result in unwanted heating of surrounding tissues, and stable
deposits provide the capability for repeated treatments over time
with a single injection. No significant nanoparticle deposits have
been identified outside of the injection site throughout the clini-
cal imaging completed to date, and stable deposits in the pros-
tate have been detectable a year after implantation (Johannsen et
al. 2010). This provides for safe, repeatable treatment.
17.5.1.3 Implantation procedure
Effective thermal treatment of a tumor requires that all areas
of the tumor are heated to a therapeutic level, and this is best
achieved through a homogenous distribution of nanoparticles.
This, in turn, requires an effective method for implantation.
Some success has been demonstrated for image-guided inter-
stitial injection, while local arterial infusion indicates potential
promise for some future applications.
Interstitial injection is most effective under some form of image
guidance. CT guidance has been used to control nanoparticle
injection in the cranium (stereotactically administered), cervi-
cal area, and other soft tissue sites, while transrectal ultrasound
(TRUS) with X-fluoroscopy guidance has been used in the pros-
tate. While these techniques have generally met with success,
some significant mechanical resistance has been encountered
in tissues that received prior radiotherapy (Wust et al. 2006;
Johannsen et al. 2010). This provided difficulty in following the
planned trajectories and raises concern over the subsequent abil-
ity of the nanoparticles to diffuse through the tissue. Overall,
however, the interstitial injection techniques have proved clini-
cally viable. Computed images of planned and actual nanopar-
ticle distributions are included in Figure 17.13, along with the
resulting temperature maps during treatment. Intraoperative
injection under direct visual and endoscopic guidance has also
been attempted, with mixed results (Wust et al. 2006; Steinbach
et al. [in draft]). Transarterial injection has demonstrated some
17.5.1.4 Magnetic Field applicator
A means of safely and effectively applying an external magnetic
field is necessary to activate the implanted nanoparticles. Major
considerations in design of such an applicator include uniformity
of field, patient comfort, and capability for treatment through-
out the body. Although multiturn inductive coils provide an
adequate platform for small animal preclinical studies, a more
robust system is required for clinical applications. Currently, the
only applicator under clinical investigation is the NanoActivator
(MagForce Nanotechnologies AG, Berlin, Germany), illustrated
in Figure 17.14. Patients are placed horizontally on the bed and
slid in the y-direction into the applicator. A ferrite yoke with pole
shoes above and below the patient is coupled with a resonant
circuit that creates an alternating magnetic field at 100 kHz. A
roughly cylindrical field with 20 cm diameter is created between
the two pole shoes. Field variability is shown in Figure 17.14. The
magnetic field strength depends linearly on the coil current and
is adjustable from 2 to 18 kA/m. An aperture can also control the
gap between the pole shoes, adjustable from 210 to 320 mm, with
some decrease in field strength for wider gaps. However, the field
is relatively homogeneous with very little radial variance.
(a)
Plan
Actual nanoparticle distribution
Puncture track
Skin
ermometry
catheter
Ta rget
Nanoparticle area
Nanoparticle deposit
Planned temperature distribution
Actual temperature distribution
(b)
FIGURE 17.13
Comparison of planned and actual nanoparticle distributions for treatment of cervical cancer (a), with resulting temperature
distributions (b). (From Wust, P. et al.,
International Journal of Hyperthermia
22, 8, 2006.)
