Acta Radiol OnlineFirst, published on April 6, 2016 as doi:10.

1177/0284185116639765

Original Article
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Determination of the electrical 2016
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DOI: 10.1177/0284185116639765
impact on therapy planning in the acr.sagepub.com

radiofrequency ablation of liver tumors

Urte Zurbuchen, Franz Poch, Ole Gemeinhardt, Martin E Kreis,

Stefan M Niehues, Janis L Vahldieck and Kai S Lehmann

Abstract
Background: Radiofrequency ablation is used to induce thermal necrosis in the treatment of liver metastases. The
specific electrical conductivity of a liver metastasis has a distinct influence on the heat formation and resulting tumor
ablation within the tissue.
Purpose: To examine the electrical conductivity s of human colorectal liver metastases and of tumor-free liver tissue in
surgical specimens.
Material and Methods: Surgical specimens from patients with resectable colorectal liver metastases were used for
measurements (size of metastases <30 mm). A four-needle measuring probe was used to determine the electrical
conductivity s of human colorectal liver metastasis (n ¼ 8) and tumor-free liver tissue (n ¼ 5) in a total of five patients.
All measurements were performed at 470 kHz, which is the relevant frequency for radiofrequency ablation. The tissue
temperature was also measured. Hepatic resections were performed in accordance with common surgical standards.
Measurements were performed in the operating theater immediately after resection.
Results: The median electrical conductivity s was 0.57 S/m in human colorectal liver metastases at a median tempera-
ture of 35.1 C and 0.35 S/m in tumor-free liver tissue at a median temperature of 34.9 C. The electrical conductivity was
significantly higher in tumor tissue than in tumor-free liver tissue (P ¼ 0.005). There were no differences in tissue
temperature between the two groups (P ¼ 0.883).
Conclusion: The electrical conductivity is significantly higher in human colorectal liver metastases than in tumor-free
liver tissue at a frequency of 470 kHz.

Keywords
Electrical conductivity, radiofrequency ablation, liver metastases
Date received: 26 October 2015; accepted: 17 February 2016

Introduction
Radiofrequency ablation (RFA) is a frequently used
treatment for primary liver tumors and liver metastases
(1,2). A challenge in RFA is the induction of ablation
zones large enough to destroy the tumor tissue with an
adequate security margin to prevent local tumor recur-
rence. The mechanisms by which tissue is destroyed by
RFA are well known (3,4). The area of the induced
thermal necrosis is significantly influenced by the prop-
erties of the treated tissue, such as blood flow in
the tissue (5) and its electrical conductivity (6).
Biological tissues have different electrical conductivities
(6,7). Haemmerich et al. measured the electrical con-
ductivity of a small number of human liver tumors
and healthy liver tissue. They showed that the electrical
Charité–Universitätsmedizin Berlin, Berlin, Germany
Corresponding author:
Urte Zurbuchen, Charité–Universitätsmedizin Berlin, Campus Benjamin
Franklin, Hindenburgdamm 30, Berlin, 12200, Germany.
Email: urte.kunz-zurbuchen@charite.de

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2 Acta Radiologica 0(0)

conductivity is higher in tumor tissue than in healthy
tissue, independent of the frequency used for measure-
ment. Any relationship between temperature and elec-
trical conductivity was not examined in this study (8).
In an earlier study, we examined the changes in elec-
trical conductivity s during tissue coagulation at the
ablative and cooling temperatures associated with
RFA (9). We used porcine liver tissue in an ex vivo
model for this study. We showed that the electrical
conductivity increased during the heating phase and
decreased continuously during the cooling phase. In a
pre-test, we completed a single conductivity measure-
ment in a human liver sample to examine the electrical
conductivity in healthy human liver tissue and in a
human liver metastasis. This measurement indicated
that the electrical conductivity of human liver tissue is
significantly different from that of porcine liver tissue.
The conductivity was higher for the liver metastasis and
lower for the healthy liver tissue compared with the
corresponding values in the porcine liver at the same
temperature.
The aim of this study was to examine the electric
conductivity s of human colorectal liver metastases
and of tumor-free liver tissue in surgical specimens.
accordance with common surgical standards. The
measurements were obtained in the operating room
immediately (3–5 min) after resection of the surgical
specimen.
The four-needle measuring probe was positioned in
the tumor (Figs. 1 and 2), and the electrical conductiv-
ity was read from the measurement bridge. The
temperature of the tissue was measured with a digital
thermometer in the middle of the tissue near the mea-
suring probe. Measurements in macroscopic tumor-
free liver tissue were performed in a similar manner
within the same surgical specimen. The surgical speci-
mens underwent a histological assessment after
measurement.
All data (tissue temperature, electrical conductivity,
histological findings, and pre-treatment chemotherapy)
were collected in a database. Statistical analyses were

Material and Methods

A wide-band 42 Hz to 5 MHz LCR (inductance,
capacitance, resistance) measurement bridge (LCR
HiTESTER 3532-50, Hioki Corporation, Ueda,
Nagano, Japan) with a four-needle measuring probe
was used to determine the electrical conductivity of
tissue samples. The physical principle of this measure-
ment is based on a model consisting of layers of air,
saline solution, and agar to simulate resistance within Fig. 1. Experimental set-up: LCR-measurement bridge
the tissue (10). This method minimizes the effects of (background left) with the measurement probe. The four-needle
polarization impedance and is commonly used in measurement probe is positioned within the tumor-free liver
tissue studies (11,12). The conductivity measurement tissue in this example. The digital thermometer (right) was used
for temperature measurement directly after the conductivity
system used in this study is described in detail by Tsai
measurement was performed.
et al. (12). In all the experiments, calibration was per-
formed with a physiological saline solution at a tem-
perature of 25 C. All measurements were performed at
470 kHz, which is the relevant frequency for RFA. We
used a small four-needle measuring probe for this study
to perform measurements in small tissue samples. The
minimum tissue diameter for this probe was 20 mm.
Surgical specimens from patients with resectable
colorectal liver metastases were used for measurements.
The inclusion criteria were resectable colorectal liver
metastases with a minimum diameter of 30 mm for a
single metastasis. Patients received detailed information
on the purpose of this study, and their written consent
was obtained. The study was approved by the Ethics
Commission of the Charité–University Medicine Berlin Fig. 2. Conductivity measurement in a colorectal liver
(EA4/020/11). Hepatic resections were performed in metastasis.

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Zurbuchen et al. 3

performed with IBM SPSS Statistics version 21 (IBM,
Ehningen, Germany). Central tendencies were calcu-
lated as medians (minimum – maximum) because
none of the parameters measured showed normal dis-
tributions. The Mann–Whitney U Test was used for
comparisons between two independent groups. The
level of significance was 0.05 (two-sided) for each stat-
istical test. To determine whether a linear correlation
existed between temperature and conductivity, we used
Pearson’s correlation coefficient.
Results
The measurements were obtained from human colorec-
tal liver metastases from five patients with a total of
eight metastases. Measurements were also performed
in tumor-free liver tissues from all surgical specimens.
Table 1 shows the results of all electrical conductivity
s measurements, including the temperature at the
time of measurement. The postoperative histological
examination confirmed colorectal adenocarcinomas
in all metastases. The tumor-free liver tissue samples
showed different grades of steatosis or fibrosis. The
measurements in all eight metastases were performed
at a median temperature of 35.1 C. The median elec-
trical conductivity s of the metastases was 0.57 S/m.
The five measurements in healthy liver tissue were per-
formed at a median temperature of 34.9 C. The median
electrical conductivity value was 0.35 S/m in the tumor-
free liver tissue. The electric conductivity was signifi-
cantly higher in the metastases than in the tumor-free
liver tissue (Table 2).
To examine whether a correlation between tempera-
ture and conductivity existed, we used Pearson’s correl-
ation coefficient. The temperature difference was 2.1 C
for liver metastases and 1 C for tumor-free liver tissue.
There was no significant correlation between tempera-
ture and conductivity in liver metastases or tumor-free
liver tissue (Pearson’s correlation: P ¼ 0.985 for liver
metastases and P ¼ 0.880 for tumor-free liver tissue).
Discussion
In this study, we examined the electrical conductivity s
in human colorectal liver metastases and in tumor-free
liver tissues from surgical specimens. We investigated
eight metastases in five patients. The median electrical
conductivity s was 0.57 S/m at a median temperature of
35.1 C for the metastases. This value was significantly
higher than the electrical conductivity of the human
tumor-free liver tissue, which was 0.35 S/m at a tem-
perature of 34.9 C.
Previous studies in various tumor models suggested
that malignant tissue has a higher electrical conductiv-
ity than normal tissues at radiofrequencies (11,13,14).
Haemmerich et al. measured electrical conductivity in a

Table 1. Electrical conductivity in colorectal liver metastases and tumor-free liver tissue.

Patient Age Temperature Specific electric

no. (years) Gender ( C) conductivity s (S/m) Histology

1 60 M Metastasis 1 37.2 0.62 Moderately differentiated

Metastasis 2 32.7 0.68 colorectal adenocarcinoma
Tumor-free 35.9 0.35 Severe mixed vesicular steatosis,
liver tissue moderate fibrosis
2 86 M Metastasis 34.0 0.44 Necrotic metastasis of a
colorectal adenocarcinoma
Tumor-free 33.9 0.26 Normal liver tissue
liver tissue
3 68 F Metastasis 1 32.5 0.51 Moderately differentiated
Metastasis 2 32.5 0.60 colorectal adenocarcinoma
Tumor-free 34.9 0.38 Marginal steatosis and fibrosis
liver tissue
4 59 F Metastasis 1 37.0 0.57 Moderately differentiated
Metastasis 2 36.1 0.56 colorectal adenocarcinoma
Tumor-free 34.6 0.46 Normal liver tissue
liver tissue
5 53 M Metastasis 36.1 0.54 Necrotic metastasis of a
colorectal adenocarcinoma
Tumor-free 35.9 0.32 Marginal steatosis and fibrosis
liver tissue

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4 Acta Radiologica 0(0)
Table 2. Statistical analysis of conductivity and temperature (two-sided Mann–Whitney U test).
Group
Colorectal liver metastases
Median Minimum
Specific electrical 0.57 0.44
conductivity s (S/m)
Temperature ( C) 35.1 32.5
small number of human liver tumors and healthy liver
tissue samples. These authors showed that the electrical
conductivity is higher in tumor tissue than in healthy
tissue, independent of the frequency used for measure-
ment (8). The relationship between temperature and
electrical conductivity was not examined in this study.
In this study, the measurements were performed
30–60 min after resection of the surgical specimen and
after the transport of tissues to the pathology lab,
where the tumor was centrally sliced to expose the
tumor core. Haemmerich determined the electrical con-
ductivity to be 0.50 S/m for tumor tissue and 0.26 S/m
for normal liver tissue at 460 kHz. The temperature of
the tissue upon measurement was not indicated. Our
results at 470 kHz, which were 0.57 S/m for tumor tis-
sues and 0.35 S/m for normal liver tissue, are slightly
higher than the values obtained by Haemmerich. Our
results confirm that the electrical conductivity is higher
in tumor tissue than in normal tumor-free tissue. We
assumed that the slightly greater electrical conductivity
in our study was due to the higher temperature in the
tissue at the time of measurement. In our experimental
set-up, the measurements were performed 3–5 min after
resection of the surgical specimen in the operating
room, and the tissue temperature was measured.
Empirical surgical specimens cool down quickly,
so we assume that the tissue temperatures in
Haemmerich’s study were lower.
In a previous study on porcine liver ex vivo, we
determined that the electrical conductivity changes
during the coagulation process (9). We showed that
the electrical conductivity s depends on the tissue tem-
perature and that the conductivity continuously
increases during the thermal coagulation process. The
maximum conductivity was reached at a temperature of
80 C. During the cooling phase, which follows coagu-
lation, the electrical conductivity was uniformly lower
than that during tissue heating. To our knowledge, no
data exist regarding the correlation between electrical
conductivity s and tissue temperature in human colo-
rectal liver metastases.
All measurements were performed in the operating
room immediately after surgical resection to ensure that
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Tumor-free liver tissue
Maximum Median Minimum Maximum P
0.68 0.35 0.26 0.46 0.005
37.2 34.9 33.9 35.9 0.883
the measurements were essentially performed at body
temperature. Cell disintegration could be excluded, as
all measurements were performed without delay after
resection.
However, this study also had some limitations. In
addition to the small sample size, we measured the con-
ductivity in liver tissue at only one specific temperature
after surgical resection. Therefore, we could not exam-
ine temperature-dependent changes, which we expect to
occur during RFA. While these data would be interest-
ing, such an approach is limited due to ethical consid-
erations. An experimental conductivity measurement
involving the coagulation process would require heat-
ing of the tumor (9), which would render a proper
pathological investigation impossible. The vasculariza-
tion of tissue was missing in our study. It is known that
the vascular perfusion of tissue has a high impact on its
biophysiological properties (5). The absence of blood
flow in the measured tissue presumably influences the
electrical conductivity. In our previous study, we
showed temperature-dependent changes in electrical
conductivity during the complete heating and cooling
phases within the RFA temperature range. We used
porcine liver samples for these ex vivo measurements.
In the present study, the temperature difference was
2.1 C for the liver metastases and 1 C for the tumor-
free liver tissue. There was no significant correlation
between temperature and conductivity in our study.
Even if we did not examine the changes in electrical
conductivity in human liver metastases during the
RFA heating and cooling phases for the reasons out-
lined above, we assumed that the trends would be the
same and that the electrical conductivity would increase
during the heating phase and decrease continuously
during the cooling phase. Other experimental studies
support this statement (15).
The heat dispersion during RFA of colorectal liver
metastases is influenced by several application param-
eters (applicator length, power settings, application
time), as well as by tissue-dependent parameters
(16,17). In addition to vascular perfusion (5), electrical
conductivity determines the depth of the heat disper-
sion in the target tissue. Several studies have shown that
Zurbuchen et al.
larger coagulation zones can be achieved by changing
the biophysiological properties of the target tissue
(18,19). Based on the knowledge that a change in elec-
trical conductivity can be achieved by saline, the per-
fusion of saline in the vicinity of radiofrequency
applicators has been performed to produce larger
coagulation zones (20) and maintain low electrical
conductivity.
Differences in the electrical conductivity between
liver metastases and tumor-free liver tissue can have a
significant impact on ablation area. The histological
analysis of the liver tissue samples in our study showed
different stages of steatosis or fibrosis. The impact of
liver histological features on the electrical conductivity
of the tissue is not clear. An impedance-controlled
therapy, which takes the changes in electrical conduct-
ivity into account, would be a reasonable approach
for an optimized ablation strategy (21). Moreover, com-
puter-aided simulation and planning tools are being
developed to enable a pre-interventional estimation of
RFA effectiveness (22,23) by using mathematical simu-
lation to model the electrical conductivity of tissues (24).
The simulation algorithms of these systems require
information related to the electrical conductivity of
target tissues for precise RFA therapy planning.
In conclusion, electrical conductivity significantly
differs between human colorectal liver metastases and
tumor-free liver tissue. The conductivity influences the
energy distribution in the target tissue during RFA.
Knowledge of the conductivity can have an impact on
RFA and can be used to optimize therapy planning.
The higher electrical conductivity of tumor tissue
should be considered in planning algorithms for
RFA. A viable option would be to directly measure
the specific conductivity before RFA. The ablation
could then be performed in an impedance-controlled
manner to reach an optimal energy input into the
target tissue.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The authors received no financial support for the research,
authorship, and/or publication of this article.
References
1. Faitot F, Faron M, Adam R, et al. Two-stage hepatect-
omy versus 1-stage resection combined with radiofre-
quency for bilobar colorectal metastases: a case-matched
analysis of surgical and oncological outcomes. Ann Surg
2014;260:822–827. (discussion 827–828).
Downloaded from acr.sagepub.com at DALHOUSIE UNIV KELLOG LIBRARY on June 5, 2016
5
2. Cirocchi R, Trastulli S, Boselli C, et al. Radiofrequency
ablation in the treatment of liver metastases from colo-
rectal cancer. Cochrane Database Syst Rev Online 2012;
6:CD006317.
3. Goldberg SN, Gazelle GS, Compton CC, et al.
Treatment of intrahepatic malignancy with radiofre-
quency ablation: radiologic-pathologic correlation. Cancer
2000;88:2452–2463.
4. Thomsen S. Pathologic analysis of photothermal and
photomechanical effects of laser-tissue interactions.
Photochem Photobiol 1991;53:825–835.
5. Lehmann KS, Ritz JP, Valdeig S, et al. Ex situ quantifi-
cation of the cooling effect of liver vessels on radiofre-
quency ablation. Langenbecks Arch Surg Dtsch Ges Für
Chir 2009;394:475–481.
6. O’Rourke AP, Lazebnik M, Bertram JM, et al. Dielectric
properties of human normal, malignant and cirrhotic
liver tissue: in vivo and ex vivo measurements from 0.5
to 20 GHz using a precision open-ended coaxial probe.
Phys Med Biol 2007;52:4707–4719.
7. Fu F, Xin SX, Chen W. Temperature- and frequency-
dependent dielectric properties of biological tissues
within the temperature and frequency ranges typically
used for magnetic resonance imaging-guided focused
ultrasound surgery. Int J Hyperth Off J Eur Soc
Hyperthermic Oncol North Am Hyperth Group 2014;
30:56–65.
8. Haemmerich D, Schutt DJ, Wright AW, et al. Electrical
conductivity measurement of excised human metastatic
liver tumours before and after thermal ablation. Physiol
Meas 2009;30:459–466.
9. Zurbuchen U, Holmer C, Lehmann KS, et al.
Determination of the temperature-dependent electric
conductivity of liver tissue ex vivo and in vivo:
Importance for therapy planning for the radiofrequency
ablation of liver tumours. Int J Hyperth Off J Eur Soc
Hyperthermic Oncol North Am Hyperth Group 2010;26:
26–33.
10. Tsai JZ, Cao H, Tungjitkusolmun S, et al. Dependence of
apparent resistance of four-electrode probes on insertion
depth. IEEE Trans Biomed Eng 2000;47:41–48.
11. Haemmerich D, Ozkan R, Tungjitkusolmun S, et al.
Changes in electrical resistivity of swine liver after occlu-
sion and postmortem. Med Biol Eng Comput 2002;40:
29–33.
12. Haemmerich D, Staelin ST, Tsai JZ, et al. In vivo elec-
trical conductivity of hepatic tumours. Physiol Meas
2003;24:251–260.
13. Surowiec AJ, Stuchly SS, Barr JB, et al. Dielectric prop-
erties of breast carcinoma and the surrounding tissues.
IEEE Trans Biomed Eng 1988;35:257–263.
14. Swarup A, Stuchly SS, Surowiec A. Dielectric properties
of mouse MCA1 fibrosarcoma at different stages of
development. Bioelectromagnetics 1991;12:1–8.
15. Wi H, McEwan AL, Lam V, et al. Real-time conductivity
imaging of temperature and tissue property changes
during radiofrequency ablation: an ex vivo model using
weighted frequency difference. Bioelectromagnetics 2015;
36:277–286.
6 Acta Radiologica 0(0)
16. Zurbuchen U, Frericks B, Roggan A, et al. Ex vivo evalu-
ation of a bipolar application concept for radiofrequency
ablation. Anticancer Res 2009;29:1309–1314.
17. Vahldiek JL, Lehmann KS, Poch F, et al. Measuring
and optimizing results in multipolar RFA: Techniques
and early findings in an experimental setting. Clin
Hemorheol Microcirc 2014;58:77–87.
18. Goldberg SN, Ahmed M, Gazelle GS, et al. Radio-
frequency thermal ablation with NaCl solution injec-
tion: effect of electrical conductivity on tissue heating
and coagulation-phantom and porcine liver study.
Radiology 2001;219:157–165.
19. Liu Z, Ahmed M, Weinstein Y, et al. Characterization of
the RF ablation-induced ‘‘oven effect’’: the importance of
background tissue thermal conductivity on tissue heating.
Int J Hyperth Off J Eur Soc Hyperthermic Oncol North
Am Hyperth Group 2006;22:327–342.
20. Clasen S, Geng A, Herberts T, et al. Internally cooled
bipolar radiofrequency ablation: is a lower power
Downloaded from acr.sagepub.com at DALHOUSIE UNIV KELLOG LIBRARY on June 5, 2016
output more effective? RöFo Fortschritte Auf Dem
Geb Röntgenstrahlen Nukl 2007;179:282–288.
21. Kröger T, Pätz T, Altrogge I, et al. Fast estimation of the
vascular cooling in RFA based on numerical simulation.
Open Biomed Eng J 2010;4:16–26.
22. Rieder C, Kroeger T, Schumann C, et al. GPU-based
real-time approximation of the ablation zone for radio-
frequency ablation. IEEE Trans Vis Comput Graph
2011;17:1812–1821.
23. Lehmann KS, Frericks BB, Holmer C, et al. In vivo val-
idation of a therapy planning system for laser-induced
thermotherapy (LITT) of liver malignancies. Int J
Colorectal Dis 2011;26:799–808.
24. Trujillo M, Berjano E. Review of the mathematical func-
tions used to model the temperature dependence of elec-
trical and thermal conductivities of biological tissue in
radiofrequency ablation. Int J Hyperth Off J Eur Soc
Hyperthermic Oncol North Am Hyperth Group 2013;
29:590–597.