Book of abstract 2008

In vivo electroporation level detection based on propidium iodide
test and magnetic resonance imaging and numerical modeling and
optimization of local electric field in muscle tissue
Selma Čorović1 ,2 ,3, Anže Županič1, Simona Kranjc4, Bassim Al Sakere2 ,3, Anne Leroy
Willig5, Lluis M. Mir2 ,3, Damijan Miklavčič1
1University of Ljubljana, Faculty of Electrical Engineering, Tržaška 25, SI-1000 Ljubljana Slovenia;
2CNRS, UMR 8121 Institute Gustave-Roussy, 39 Rue C. Desmoulins, F-94805 Villejuif, France; 3Univ
Paris-Sud, UMR 8121; 4Institute of Oncology, Zaloška 2, SI-1000 Ljubljana, Slovenia; 5Univ Paris-Sud
Faculté d’Orsay, UMR 808, U2R2M, Batiment 220, F-91405 Orsay Cedex, France
The aim of this study was to experimentally and numerically analyze local electric field
distribution in anisotropic tissues to be electroporated for biomedical purposes. Indeed,
in vivo electroporation (electropermeabilization) is an effective technique for delivery of
therapeutic drugs or DNA molecules into the target tissue cells by means of local application
of high voltage electric pulses via appropriate electrode configuration. Solid tumors are
treated with electrochemotherapy (ECT) in routine in clinics, and several types of tissues
can be transfected with foreign DNA by means of gene electrotransfer (EGT).
The level of the tissue electroporation and the distribution of the electric fields can be
optimized so that the increase in cell membrane permeability can be limited to the cells of
the target tissue while minimizing the damage to the surrounding tissue, which is essential
in electrochemotherapy and gene electrotransfer treatment planning. The key parameter
in effective tissue electroporation is local electric field distribution (E) induced by the
application of short and intense electric pulses. In order to assure successful ECT and
EGT outcome the entire tissue to be treated has to be optimally electroporated, which
requires an adequate electric field within the treated tissue. This means that in ECT and
EGT treatment planning the following requirements have to be met: 1) all the target
tissue has to be subjected to the local electric field (E) inducing reversible electroporation
(E between reversible and irreversible thresholds E rev
< E < E irrev
) while 2) the surrounding
tissue should not be exposed to excessively high local electric field (E > E irrev
). The E rev
and
E irrev
thresholds need to be determined experimentally.
In this study we experimentally and numerically determined the E rev
and E irrev
threshold
values for muscle tissue taking into account its anisotropic electric properties. The
experiments were carried out in vivo by means of a fluorescence test using propidium
iodide, and magnetic resonance imaging detecting the electrotransfer inside the cells of an
extracellular contrast agent. Electroporation of mouse anterior tibialis was examined for
parallel and perpendicular directions of the electric field with respect to the muscle fibers.
Based on this we determined the reversible and irreversible elelectropermeabilisation
threshold values - E rev
and E irrev
- in both directions. These values were included in 3D
numerical model of muscle tissue. The numerical analysis was carried using finite element
method. We developed an optimization genetic algorithm for optimization of local
electric field in anisotropic tissues, which can serve as an important tool in ECT and EGT
p1193
treatment planning. The results of our experimental study can significantly contribute to
the understanding of in vivo electroporation also of anisotropic tissues.