2297_2969_CIBECabstr..

advertisement
Experimental and Numerical Characterization of a Tissue Lesion
Induced by a Tubular Electrode
Carlos L. Antunes, MIEEE, Tony R. Almeida, Nélia Raposeiro, Belarmino Gonçalves, and Paulo
Almeida

Abstract—Radiofrequency ablation of tumors on hollow
organs using tubular electrodes made out of a self-expandable
metal stent has been shown as a feasible experimental
procedure. In order to achieve a better understanding of this
method, ex-vivo experimentation and numerical simulation
were performed to characterize the lesion induced in the tissue
next to this kind of electrodes. From the experimental data it
was possible to adjust a numerical model which reassembles
with some precision the results obtained by experimentation
I. INTRODUCTION
C
is actually a major cause of death worldwide.
The International Agency for Research on Cancer
(IARC) estimated that about 8 million people will die during
2010 because of cancer, and 12.7 million of new cases will
be diagnosed. By 2030 it is expected that these numbers
increase to 21.4 million incident cases of cancer and 13
million cancer deaths [1].
Colorectal cancer accounts for 8% of all cancer deaths,
making it the fourth most common cause of death from
cancer. About 20% of colorectal cancers are diagnosed as a
disseminated disease, and the majority of metastatic patients
have unresectable cancer. In these cases, as well as for
patients with colonic obstruction and incurable metastases,
surgery is palliative and the use of self-expanding metallic
stents (SEMS) seems reasonable option [2].
Esophageal cancer is the eighth most common cancer
worldwide and, with its very poor survival rate, it is the sixth
most common cause of death from cancer. More than 50%
of patients with esophageal carcinoma are found to be
incurable at the time of diagnosis. For these cases palliative
cares are the choice and SEMS are effective option for
relieving symptoms and improving quality of life [3].
Liver cancer has a very poor prognosis, being the number
ANCER
Manuscript received June XX, 2010. This work was financially
supported by the Foundation for Science and Technology (FCT, Portugal)
through the project number PTDC/EEA-ACR/72276/2006.
C. L. Antunes is with the Department of Electrical Engineering and
Computer Science, University of Coimbra, 3030-290 Coimbra
PORTUGAL. He is also with RIANDA Research – Centro de Investigação
em Energia, Saúde e Ambiente, 3030-281 Coimbra PORTUGAL (phone:
+351 239 780 237; e-mail: lemos.antunes@apdee.org).
T. R. Almeida is with the Department of Electrical Engineering and
Computer Science, University of Coimbra, 3030-290 Coimbra PORTUGAL
(e-mail: tony@deec.uc.pt).
N. Raposeiro is with RIANDA Research – Centro de Investigação em
Energia, Saúde e Ambiente, 3030-281 Coimbra PORTUGAL.
B. Gonçalves is with Hospitais Universitários de Coimbra, Coimbra,
PORTUGAL.
P. Almeida is with Hospital de Santo André, Leiria, PORTUGAL.
of deaths almost the same as the number of new cases. It is
therefore the third most common cause of death from cancer
[4]. Cholangiocarcinoma is a malignant cancer arising from
the neoplastic transformation of the epithelial cells lining the
intra-hepatic and extra-hepatic bile ducts, and it is the
second most common primary hepatic malignancy [5].
Because there are no early symptoms, the majority of
patients are diagnosed at advanced stage, when surgical
therapies are excluded [6]. Biliary obstruction in patients
with unresectable cholangiocarcinoma can usually be
managed by percutaneous or endoscopic SEMS because of
their feasibility [7].
In recent years, radiofrequency (RF) ablation has been
used as a promising minimally invasive treatment method
for primary and metastatic liver tumor, and its application
has been extended with some success for the treatment of
small renal carcinomas [8, 9], lung [10], breast [11] and
bone tumors [12]. In these medical procedures, the targeted
tissue to be treated is massy and so the electrodes used are
needle-based [13]. On the other hand, these needle-based
electrodes might be hard to apply in tumors that are located
in hollow organs, like the esophagus, colon or bile duct. For
these cases, previous work showed [14, 15] that, besides
SEMS can be used not only as a part of mechanical
palliative procedure, it can be used as an electrode itself.
In this work it is intended to characterize the lesion size
that this kind of electrode can produce and, from the
experimental data, to obtain and validate a numerical model
that helps to estimate the volume lesion.
II. MATERIALS AND METHODS
A. Electrical conductivity measurement
The measurements were performed using the fourelectrode method [16]. The electrodes were made from
0.4 mm diameter silver wire, coated with AgCl to reduce
artifacts due to electrode polarization (Ag/AgCL electrodes).
The electrodes were placed in a straight line with a 1.5 mm
distance between. The two outer electrodes were used to
inject current in the tissue and they were connected to a
current-to-voltage amp-op circuit. The inner electrodes, that
were used to measure the voltage, were connected to an
instrumentation amplifier. The outputs of both circuits were
read using a Tektronics TDS 1002 oscilloscope.
For each liver they were made 2 to 5 measurements in 5 to
10 different points, performing almost 500 measurements.
All measurements were performed at a frequency of
470 kHz, which corresponds to the output voltage frequency
of the ValleyLab RF power generator used during
experimentation.
Fig. 1. The four-electrode probe made for measuring the electrical
conductivity.
B. Ex-vivo experimentation
Experimental work was performed on bovine livers
collected at a local slaughter house, approximately two hours
after abating the animals. In each liver a vertical hole with 89 mm of diameter was made in the center of it for placing
the electrode.
A biliar SEMS from Boston Scientific with a diameter of
10 mm and a length of 40 mm was used as electrode. The
stent was placed in the liver and it was connected to the RF
generator through a BI-PAL endoscopic biopsy. This forceps
consists of a 3-pull ring handle, stainless steel cutting jaws,
and a coiled shaft. An electrical wired was soldered to the
forceps’ shaft, which is electrically connected to the jaws
(Fig. 2). This way the electrode can be placed properly,
achieving the electrical connection to the RF generator using
the forceps’ jaws on the stent.
Two RTD temperature sensors were placed at 1 and 2 cm
of the electrode. A National Instruments NI USB-9219
acquisition board was used to read these sensors and the data
was registered with LabVIEW SignalExpress software.
Also, voltage, current intensity and electrical impedance
measured by the RF generator were registered.
(a)
(b)
Fig. 2. (a) forceps BI-PAL; (b) detail of the electrical connection.
Fig. 3. Experimental setup.
To obtain a current distribution around the electrode as
symmetric as possible, a return pad was placed at each end
of the liver. The RF generator was set to impedance control
mode. Fig. 2 presents one of the typical setups used along
the experimental test performed.
There were performed RF ablation procedures for 5, 10
and 15 minutes, using an output voltage of 25, 50, 75 and
100V. After each procedure, the liver was cross sectioned
along a plane containing the stent axis for measuring the
dimension of the lesion induced. No histological
examination was involved but visual observation.
C. Numerical modeling
The numerical simulation of the models consists on the
analysis of a thermoelectrical coupled field problem. The
temperature at each point of the tissue can be expressed by a
simplified bioheat equation [14, 15]:
c
T
   k T  J  E
t
(1)
where ρ is the density (kg/m3), c is the specific heat (J/kg·K),
T is the temperature (K), k is thermal conductivity (W/m·K),
J is the current density (A/m) and E electric field intensity
(V/m). The right most term of (1) corresponds to the
electrode energy. At RF frequencies the quasi-static
approximation is valid and the biological tissue can be
considered as a resistive material [17]. A RF voltage is
applied between the stent and the return pad and the
resulting voltage through the domain obeys Laplace’s
equation:
  V  0
(2)
where σ is the electrical conductivity (S/m) and V is the
electric potential (V).
Fig. 4. Geometrical model used for numerical simulation.
A cylindrical model of 100 mm radius and 80 mm height
was created for representing the liver tissue. At the center a
second cylinder of radius 5 mm and height of 55 mm
represents the hollow. The electrode is place at the bottom of
the hole and its dimensions are 40 mm length and 10 mm
diameter. The stent is made from 24 nitinol wires with
0.25 mm diameter. Each wire is a helix with a pitch of
25 mm. Twelve of the helices are clockwise and the others
are counter-clockwise. The whole model have a total of
184 117 tetrahedra.
The electrical potential applied to the stent is constant
during all RF ablation procedure. Simulations were
performed considering voltage values of 25, 50, 75 and
100 V. The bottom and the sides of the larger cylinder are
considered at zero volts.
The material properties used in our model are presented in
TABLE I [18]. The electrical conductivity of the tissue was
considered temperature-dependent and simulation was
performed considering temperature coefficient of 2%/ºC.
When temperature reaches 100ºC, electrical conductivity
abruptly drops. By this way it is possible to simulate the
electrical insulation verified when gas forms at this
temperature value [19].
Element
Electrode
Hole
Tissue
TABLE I
MATERIAL PROPERTIES USED IN SIMULATION [18]
Material
ρ [kg/m3]
c[J/kg·K]; k[W/m·K]
Nitinol
6450
840
18
Air
1.202
1
0.025
Liver
1060
3600
0512
σ[S/m]
1·108
0
σ(T)
Dirichlet boundary conditions for the temperature were set
to 22ºC for the surfaces away from the active electrode,
except for the bottom plane, considered as a thermal
insulator surface. The initial temperature of the tissue was
set to 25ºC.
The models were solved using the solver PARDISO
implemented in the finite element software COMSOL
Multiphysics (COMSOL, Inc. Burlington, MA, USA).
Solving time took about 2.21 hours at 25 V, and 15 hours at
100 V. It was used a computer with a Intel Core 2 Quad
CPU @ 2.34Ghz, with 8Gb of RAM, on a 64 bits platform.
generator when its 999Ω security threshold is exceeded. This
is due to the carbonization of the tissue next to the electrode
which induces its electrical insulation.
As it would be expected, temperature in the tissue starts to rise as soon
as a voltage is applied. This temperature increase will depend on the
time of the procedure and on the applied voltage. However,
independently of the time considered, no lesion was induced in the
tissue for an applied voltage of 25 V. It is shown in (a) (b)
Fig. 5 (a) the result of a RF ablation procedure after 15 minutes at 25 V.
Inspection shows that no lesion was induced in the tissue next to the
electrode. On the other hand, in
(a) (b)
Fig. 5 (b) is visible the lesion induced in the tissue for an
applied voltage of 75 V during 15 minutes.
Fig. 6 displays the averaged maximum temperature values
measured one and two centimeters away from the stent after
5, 10 and 15 minutes. Considering that cellular damage can
be attained in a few minutes for a temperature of 50-52ºC
[13, 20], it is possible to verify that the 50ºC threshold will
be hardly exceeded at 2 cm from the electrode after 5
minutes for any applied voltage.
(a)
(b)
III. RESULTS
A. Experimental results
All the data gathered from the measurement of the
electrical conductivity in all the samples of liver used was
averaged and standard deviation was calculated, thus
reaching electrical conductivity value of 0.13±0.06 S/m.
(c)
Fig. 6. Averaged maximum temperatures obtained 1 and 2 cm
away from the electrode after (a) 5 minutes; (b) 10 minutes; and (c)
15 minutes.
(a)
(b)
Fig. 5. (a) Tissue after 15 minutes at an applied voltage of 25 V. It
is observed the no damage was induced in the tissue next to the
electrode; (b) Tissue damage after 15 minutes at 75 V.
In each experimental RF ablation procedure it was
possible to observe that the electrical current supplied by the
RF power source increased with time, thus increasing the
power supplied. This fact consequence of the electrical
impedance drop measured from the RF generator. This was
not totally verified at 100 V because the RF generator
reaches its maximum current output of 2 A. Also, at 100 V
the electrical impedance inverts its decrease tendency above
10 minutes, sometimes leading to the shutdown of the power
Fig. 7. Cylindrical volume approximation of the lesion induced in
the tissue. Numerical and experimental results.
After each RF ablation procedure, the liver was cross
sectioned and the height and the maximum width of the
lesion induced were measured. The volume of the lesion was
calculated and approximated to a cylindrical volume. Fig. 7
shows the average volume obtained considering the voltage
applied and the time of the procedure (experimental results
in solid line). As expected, a bigger lesion is obtained
considering larger values of voltage and/or time. For 100 V
it is possible to observe that the lesion volume does not
significantly change in size after 10 minutes.
B. Numerical simulation
In Fig. 7 are shown the results obtained by numerical
simulation. No results are presented for an applied voltage of
25 V because, even after 15 minutes, the temperature of the
tissue never reached 50ºC so no lesion is induced in tissue.
The volume of the lesion obtained by analysis of the
numerical results almost agrees with measurements made
after experimental procedure. However these results diverge
for an applied voltage of 100 V, for which the volume
obtained with numerical simulation after 5 and 10 minutes is
considerable
larger
than
the
volume
obtained
experimentally. After 15 minutes, volumes obtained
numerically and experimentally are close.
IV. CONCLUSION
Due to its good mechanical and biocompatibility
characteristics, nitinol SEMS is a popular endoprothesis
used for relieving stricture problems in hollow organs due to
carcinomas. Besides its mechanical application, SEMS can
be regarded as well as potential electrode for performing RF
ablation therapy on the tumor. In this work numerical and
experimental analyses were performed in order to
characterize the lesion volume induced in biological tissue
using this kind of tubular electrode.
Results show that it is possible to achieve a regular lesion
around the electrode. The volume of the lesion obviously
depends on the voltage applied and the time of the
procedure. Also, the volume of damaged tissue obtained can
be considerable large which means precautions have to be
taken in order not to injure the duct organ involved. Results
obtained through numerical simulations are very close to
those obtained with experimentation, providing this way an
important tool to predict the dimension that might be
obtained and in order to plan a RF ablation procedure.
The temperature dependence of thermal properties of the
tissue was not considered in this work due to the lack of data
on this subject. Thus, this limitation of our model may lead
to some inaccurate results, particularly for an applied voltage
of 100 V. In this case, the rapidly temperature increase near
the electrode may affect significantly the thermal and even
the electrical properties of the tissue, which might explain
the divergence between numerical and experimental results.
However, considering the fragility of the hollow organs that
undergo RF ablation procedure and the power that is
delivered at 100 V, this voltage certainly will be hardly
considered.
ACKNOWLEDGMENT
The authors would like to thank Dr. Nuno Pinto from
Matadouro da Beira Litoral (Aveiro, Portugal) for his
support on obtaining the liver samples used in this work.
REFERENCES
[1] J. Ferlay, et al. (2010, June 5th). GLOBOCAN 2008, Cancer Incidence
and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Available:
http://globocan.iarc.fr/
[2] J. Súarez, et al., "Stent or surgery for incurable obstructive colorectal
cancer: an individualized decisión," International Journal of Colorectal
Disease, vol. 25, pp. 91-96, 2010.
[3] M. Burstow, et al., "Outcome of palliative esophageal stenting for
malignant dysphagia: a retrospective analysis," Diseases of the Esophagus,
vol. 22, pp. 519-525, 2009.
[4] D. M. Parkin, et al., "Global Cancer Statistics, 2002," CA Cancer
Journal for Clinicians, vol. 55, pp. 74-108, March 1, 2005.
[5] M. Gatto, et al., "Cholangiocarcinoma: Update and future
perspectives," Digestive and Liver Disease, vol. 42, pp. 253-260, April
2010.
[6] M. Gatto and D. Alvaro, "New insights on cholangiocarcinoma," World
Journal of Gastrointestinal Oncology, vol. 2, pp. 136-145, March 15 2010.
[7] W. H. Paik, et al., "Palliative treatment with self-expandable metallic
stents in patients with advanced type III or IV hilar cholangiocarcinoma: a
percutaneous versus endoscopic approach," Gastrointestinal Endoscopy,
vol. 69, pp. 55-62, 2009.
[8] E. M. Merkle, et al., "Renal Cell Carcinoma: Follow-Up with Magnetic
Resonance Imaging After Percutaneous Radiofrequency Ablation," in
Methods of Cancer Diagnosis, Therapy, and Prognosis. vol. 6, ed: Springer
Netherlands, 2010, pp. 108-113.
[9] R.-T. Hoffmann, et al., "Renal cell carcinoma in patients with a solitary
kidney after nephrectomy treated with radiofrequency ablation: Mid term
results," European Journal of Radiology, vol. 73, pp. 652-656, 2010.
[10] L. Crocetti and R. Lencioni, "Radiofrequency ablation of pulmonary
tumors (in press)," European Journal of Radiology, 2010.
[11] T. Kinoshita, et al., "Radiofrequency ablation as local therapy for early
breast carcinomas," Breast Cancer, 2010.
[12] D. Volkmer, et al., "The Use of Radiofrequency Ablation in the
Treatment of Musculoskeletal Tumors (abstract)," Journal of the American
Academy of Orthopaetic Surgeons, vol. 17, pp. 737-743, December 1, 2009.
[13] Y. Ni, et al., "A review of the general aspects of radiofrequency
ablation," Abdominal Imaging, vol. 30, pp. 381-400, August 2005 2005.
[14] C. F. L. Antunes, et al., "Thermal Ablation in Biological Tissue Using
Tubular Electrode," presented at the 14th Biennial IEEE Conference on
Electromagnetic Field Computation, Chicago, USA, 2010.
[15] C. F. L. Antunes, et al., "Effects of the Geometry of a Tubular
Electrode on the Temperature Distribution in Biologial Tissue," presented at
the 14th Biennial IEEE Conference on Electromagnetic Field Computation,
Chicago, USA, 2010.
[16] W. M. Telford, et al., "Resistivity Methods," in Applied Geophysics, 2
ed: Cambridge University Press, 1990, pp. 522-539.
[17] R. Plonsey and D. Heppner, "Considerations of quasi-stationarity in
electrophysiological systems," Bulletin of Mathematical Biology, vol. 29,
pp. 657-664, 1967.
[18] D. Haemmerich, et al., "Hepatic bipolar radio-frequency ablation
between separated multiprong electrodes," IEEE Transactions on
Biomedical Engineering, vol. 48, pp. 1145-1152, 2001.
[19] D. Haemmerich, et al., "Hepatic radiofrequency ablation with internally
cooled probes: effect of coolant temperature on lesion size," IEEE
Transactions on Biomedical Engineering, vol. 50, pp. 493-500, April 2003
2003.
[20] S. N. Goldberg, "Radiofrequency tumor ablation: principles and
techniques," European Journal of Ultrasound, vol. 13, pp. 129-147, 2001.
Download