Optimization of electrode position and electric pulse amplitude in electrochemotherapy
Background. In addition to the chemotherapeutic drug being present within the tumor during electric pulse delivery, successful electrochemotherapy requires the entire tumor volume to be subjected to a sufficiently high electric field, while the electric field in the surrounding healthy tissue is as low as possible to prevent damage. Both can be achieved with appropriate positioning of the electrodes and appropriate amplitude of electric pulses.
Methods. We used 3D finite element numerical models and a genetic optimization algorithm to determine the optimum electrode configuration and optimum amplitude of electric pulses for treatment of three subcutaneous tumor models of different shapes and sizes and a realistic brain tumor model acquired from medical images.
Results. In all four tumor cases, parallel needle electrode arrays were a better choice than hexagonal needle electrode arrays, since their utilization required less electric current and caused less healthy tissue damage. In addition, regardless of tumor geometry or needle electrode configuration, the optimum depth of electrode insertion was in all cases deeper than the deepest part of the tumor.
Conclusions. Our optimization algorithm was able to determine the best electrode configuration in all four presented models and with further improvement it could be a useful tool in clinical electrochemotherapy treatment planning.
Mir LM, Gehl J, Sersa G, et al. Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator (TM) by means of invasive or non-invasive electrodes. Eur J Cancer Suppl 2006; 4: 14-25.
Snoj M, Rudolf Z, Cemazar M, Jancar B, Sersa G. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. AntiCancer Drugs 2005; 16: 345-8.
Sersa G, Cemazar M, Miklavcic D, Rudolf Z. Electrochemotherapy of tumours. Radiol Oncol 2006; 40: 163-74.
Miklavcic D, Beravs K, Semrov D, Cemazar M, Demsar F, Sersa G. The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys J 1998; 74: 2152-8.
Miklavcic D, Semrov D, Mekid H, Mir LM. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim Biophys Acta 2000; 1523: 73-83.
Miklavcic D, Corovic S, Pucihar G, Pavselj N. Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. Eur J Cancer Suppl 2006; 4: 45-51.
Pavselj N, Bregar Z, Cukjati D, Batiuskaite D, Mir LM, Miklavcic D. The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals. IEEE Trans Biomed Eng 2005; 52: 1373-81.
Sel D, Lebar AM, Miklavcic D. Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization. IEEE Trans Biomed Eng 2007; 54: 773-81.
Gilbert RA, Jaroszeski MJ, Heller R. Novel electrode designs for electrochemotherapy. Biochim Biophys Acta 1997; 1334: 9-14.
Domenge C, Orlowski S, Luboinski B, DeBaere T, Schwaab G, Belehradek J, et al. Antitumor electrochemotherapy - New advances in the clinical protocol. Cancer 1996; 77: 956-63.
Heller R, Gilbert R, Jaroszeski MJ. Clinical applications of electrochemotherapy. Adv Drug Deliv Rev 1999; 35: 119-29.
Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev 2003; 29: 371-87.
Tijink BM, De Bree R, Van D, Leemans CR. How we do it: Chemo-electroporation in the head and neck for otherwise untreatable patients. Clin Otolaryngol 2006; 31: 447-51.
Marty M, Sersa G, Garbay JR, et al. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. Eur J Cancer Suppl Nov 2006; 4: 3-13.
Sersa G. The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical uses. Eur J Cancer Suppl 2006; 4: 52-9.
Cukiati D, Batiuskaite D, Andre F, Miklavcic D, Mir LM. Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry 2007; 70: 501-7.
Pliquett UF, Vanbever R, Preat V, Weaver JC. Local transport regions (LTRs) in human stratum corneum due to long and short ‘high voltage’ pulses. Bioelectrochem Bioener 1998; 47: 151-61.
Al Sakere B, Bernat C, Connault E, Opolon O, Rubinsky B, Davalos R, et al. Tumour ablation with irreversible electroporation. PLoS ONE 2007:11.
Corovic S, Pavlin M, Miklavcic D. Analytical and numerical quantification and comparison of the local electric field in the tissue for different electrode configurations. Biomed Eng Online 2007; 6.
Miklavcic D, Pavselj N, Hart FX. Electric properties of tissues. Wiley Encyclopedia of Biomedical Engineering. New York: John Wiley & Sons; 2006.
Semrov D, Miklavcic D. Calculation of the electrical parameters in electrochemotherapy of solid tumours in mice. Comput Biol Med 1998; 28: 439-48.
Holland JH. Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence. Cambridge: MIT Press; 1992.
Gehl J, Geertsen PF. Palliation of haemorrhaging and ulcerated cutaneous tumours using electrochemotherapy. Eur J Cancer Suppl 2006; 4: 35-7.
Gehl J, Sorensen TH, Nielsen K, Raskmark P, Nielsen SL, Skovsgaard T, et al. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys Acta 1999; 1428: 233-40.
Sersa G, Cemazar M, Semrov D, Miklavcic D. Changing electrode orientation improves the efficacy of electrochemotherapy of solid tumors in mice. Bioelectrochem Bioener 1996; 39: 61-6.
Sel D, Mazeres S, Teissie J, Miklavcic D. Finite-element modeling of needle electrodes in tissue from the perspective of frequent model computation. IEEE Trans Biomed Eng 2003; 50: 1221-32.
Zupanic A, Ribaric S, Miklavcic D. Increasing the repetition frequency of electric pulse delivery reduces unpleasant sensations that occur in electrochemotherapy. Neoplasma 2007; 54: 246-50.
Puc M, Corovic S, Flisar K, Petkovsek M, Nastran J, Miklavcic D. Techniques of signal generation required for electropermeabilization. Survey of electropermeabilization devices. Bioelectrochemistry 2004; 64: 113-24.