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Electroporation

Towards Electroporation Based Treatment Planning Considering Electric Field Induced Muscle Contractions (189-201)

The electric field threshold for muscle contraction is two orders of magnitudes lower than that for electroporation. Current electroporation treatment planning and electrode design studies focus on optimizing the delivery of electroporation electric fields to the targeted tissue. The goal of one part of this study was to investigate the relation between the volumes of tissue that experience electroporation electric fields in a targeted tissue volume and the volumes of tissue that experience muscle contraction inducing electric fields around the electroporated tissue volume, (VMC), during standard electroporation procedures and for various electroporation electrodes designs. The numerical analysis shows that conventional electroporation protocols and electrode design can generate muscle contraction inducing electric fields in surprisingly large volumes of non-target tissue, around the electroporation treated tissue. In studying various electrode configurations, we found that electrode placement in a structure we refer to as a “Current Cage” can substantially reduce the volume of non-target tissue exposed to electric fields above the muscle contraction threshold. In an experimental study on a tissue phantom we compare a commercial two parallel needle electroporation system with the Current Cage design. While tissue electroporated volumes were similar, VMC of tissue treated using the Current Cage design electrodes was an order of magnitude smaller than that using a commercially available system. An important aspect of the entire study is that it suggests the benefit of including the calculations of VMC for planning of electroporation based treatments such as DNA vaccination, electrochemotherapy and irreversible electroporation.

Key words: Electroporation; DNA vaccination; Electrochemotherapy; Electrode configuration; Muscle contraction; Current Cage.





This article can be cited as:
Golberg, A. Rubinsky, B. Towards Electroporation Based Treatment Planning Considering Electric Field Induced Muscle Contractions Technol Cancer Res Treat. 11, 189-201 (2012). DOI: 10.7785/tcrt.2012.500249

References

1. Neumann, E., Schaefer-Ridder, M., Wang, Y., Hofschneider, P. H. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO Journal 1, 841-845 (1982).
2. Pucihar, G., Krmelj, J., Rebersek, M., Napotnik, T., Miklavcic, D. Equivalent Pulse Parameters for Electroporation. Biomedical Engineering, IEEE Transactions on 58, 3279-3288 (2011).
3. Ongaro, A., Pellati, A., Caruso, A., Battista, M., De Terlizzi, R., De Mattei, M., Fini, M. Identification of In Vitro Electropermeabilization Equivalent Pulse Protocols. Techology in Cancer Research and Treatment 10, 465-473 (2011).
4. Schoenbach, K., Joshi, R., Beebe, S., Baum, C. A scaling law for membrane permeabilization with nanopulses. Dielectrics and Electrical Insulation, IEEE Transactions on 16, 1224-1235 (2009). [Crossref]
5. Mir, L. M. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry 53, 1-10 (2001). [Crossref]
6. Titomirov, A. V., Sukharev, S., Kistanova, E. In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochimica et Biophysica Acta 1088, 131-134 (1991). [Crossref]
7. Okino, M., Mohri, H. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Japanese Journal of Cancer Research 78, 1319-1321 (1987).
8. Orlowski, S., Belehradek, J., Jr., Paoletti, C., Mir, L. M. Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochemical Pharmacology 37, 4727-4733 (1988).
9. Mir, L. M., Gehl, J., Sersa, G., Collins, C. G., Garbay, J.-R., Billard, V., Geertsen, P. F., Rudolf, Z., O’Sullivan, G. C., Marty, M. 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 CliniporatorTM by means of invasive or non-invasive electrodes. European Journal of Cancer 4, 14-25 (2006). [Crossref]
10. Edhemovic, I., Gadzijev, E. M., Brecelj, E., Miklavcic, D., Kos, B., Zupanic, A., Mali, B., Jarm, T., Pavliha, D., Marcan, M., Gasljevic, G., Gorjup, V., Music, M., Vavpotic, T. P., Cemazar, M., Snoj, M., Sersa, G. Electrochemotherapy: a New Technological Approach in Treatment of Metastases in the Liver. Technology in cancer research & treatment, 475-485 (2011).
11. Mir, L. M., Orlowski, S. P. Mechanisms of electrochemotherapy. Advanced Drug Delivery Reviews 35, 107-118 (1999).
12. Jaroszeski, M. J., Dang, V., Pottinger, C., Hickey, J., Gilbert, R., Heller, R. Toxicity of anticancer agents mediated by electroporation in vitro. Anti-Cancer Drugs 11, 201-208 (2000). [Crossref]
13. van Drunen Littel-van den Hurk, S., Hannaman, D. Electroporation for DNA immunization: clinical application. Expert Review of Vaccines 9, 503-517 (2010). [Crossref]
14. Vasan, S., Hurley, A., Schlesinger, S. J., Hannaman, D., Gardiner, D. F., Dugin, D. P., Boente-Carrera, M., Vittorino, R., Caskey, M., Andersen, J., Huang, Y., Cox, J. H., Tarragona-Fiol, T., Gill, D. K., Cheeseman, H., Clark, L., Dally, L., Smith, C., Schmidt, C., Park, H. H., Kopycinski, J. T., Gilmour, J., Fast, P., Bernard, R., Ho, D. D. Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers. PLoS ONE 6, e19252 (2011).
15. Drabick, J. J., Glasspool-Malone, J., Somiari, S., King, A., Malone, R. W. Cutaneous Transfection and Immune Responses to Intradermal Nucleic Acid Vaccination Are Significantly Enhanced by in Vivo Electropermeabilization. Molecular Therapy 3, 249-255 (2001). [Crossref]
16. NIH. Clinical trials http://clinicaltrials.gov. Accessed Dec. 4, 2011. (2011).
17. Miklavcic, D., Pucihar, G., Pavlovec, M., Ribaric, S., Mali, M., Macek-Lebar, A., Petkovsek, M., Nastran, J., Kranjc, S., Cemazar, M., Sersa, G. The effect of high frequency electric pulses on muscle contractions and antitumor efficiency in vivo for a potential use in clinical electrochemotherapy. Bioelectrochemistry 65, 121-128 (2005). [Crossref]
18. Roos, A.-K., Eriksson, F., Walters, D. C., Pisa, P., King, A. D. Optimization of Skin Electroporation in Mice to Increase Tolerability of DNA Vaccine Delivery to Patients. Molecular Therapy 17, 1637-1642 (2009). [Crossref]
19. El-Kamary, S. S., Billington, M., Deitz, S., Colby, E., Rhinehart, H., Wu, Y., Blackwelder, W., Edelman, R., Lee, A., King, A. Safety and Tolerability of the Easy Vax[trade] Clinical Epidermal Electroporation System in Healthy Adults. Molecular Therapy (2011). [Crossref]
20. Rubinsky, B. Irreversible Electroporation (Springer, 2010).
21. Lee, E. W., Thai, S., Kee, S. T. Irreversible Electroporation: A Novel Image-Guided Cancer Therapy. Gut Liver 4(Suppl. 1), S99-S104 (2010). [Crossref]
22. Davalos, R. D., Mir, L. M., Rubinsky, B. Tissue ablation with Irreversible Electroporation. Annals of Biomedical Engeneering 33, 223-231 (2005). [Crossref]
23. Edd, J. F., Horowitz, L., Davalos, R. D., Mir, L. M., Rubinsky, B. In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE T Biomed Eng 153, 1409-1415 (2006). [Crossref]
24. Pavselj, N., Miklavcic, D. Resistive heating and electropermeabilization of skin tissue during in vivo electroporation: A coupled nonlinear finite element model. International Journal of Heat and Mass Transfer 54, 2294-2302 (2011). [Crossref]
25. Garcia, P., Rossmeisl, J. J., Neal, R., 2nd, Ellis, T., Davalos, R. A Parametric Study Delineating Irreversible Electroporation from Thermal Damage Based on a Minimally Invasive Intracranial Procedure. Biomedical Engineering Online (2011). [Crossref]
26. Rubinsky, B. Irreversible electroporation in medicine. Tech Cancer Res Treat 6, 255-260 (2007).
27. Onik, G., Mikus, P., Rubinsky, B. Irreversible electroporation: implications for prostate ablation. Technology in Cancer Research & Treatment 6, 295-300 (2007).
28. Rubinsky, B., Onik, G., Mikus, P. Irreversible Electroporation: A New Ablation Modality – Clinical Implications. Technology in Cancer Research and Treatment 6, 37-48 (2007).
29. Garcia, P., Pancotto, T., Rossmeisl, J. J., Henao-Guerrero, N., Gustafson, N., Daniel, G., Robertson, J., Ellis, T., Davalos, R. Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol Cancer Res Treat 10, 73-83 (2011).
30. Neal, R., 2nd, Singh, R., Hatcher, H., Kock, N., Torti, S., Davalos, R. Treatment of breast cancer through the application of irreversible electroporation using a novel minimally invasive single needle electrode. Breast Cancer Res Treat 123, 295-301 (2010). [Crossref]
31. Thomson, K. in Irreversible Electroporation (Ed. B. Rubinsky) 249-254 (Springer, 2010).
32. Ball, C., Thomson, K., Kavnoudias, H. Irreversible Electroporation: A New Challenge in “Out of Operating Theater” Anesthesia. Anesth Analg 110, 1305-1309 (2010). [Crossref]
33. Deodhar, A., Dickfeld, T., Single, G. W., Hamilton, W. C., Thornton, R. H., Sofocleous, C. T., Maybody, M., Gonen, M., Rubinsky, B., Solomon, S. B. Irreversible Electroporation Near the Heart: Ventricular Arrhythmias Can Be Prevented With ECG Synchronization. American Journal of Roentgenology 196, W330-W335 (2011). [Crossref]
34. Despa, F., Basati, S., Zhang, Z. D., D’Andrea, J., Reilly, J. P., Bodnar, E. N., Lee, R. C. Electromuscular Incapacitation Results From Stimulation of Spinal Reflexes. Bioelectromagnetics 30, 411-421 (2009). [Crossref]
35. Joshi, R. P., Mishra, A., Xiao, S., Pakhomov, A. Model Study of Time-Dependent Muscle Response to Pulsed Electrical Stimulation. Bioelectromagnetics 31, 361-370 (2010). [Crossref]
36. Rogers, W. R., Merrit, J. H., Comeaux, J. A., Kuhnel, C. T., Moreland, D. F., Teltschik, D. G., Lucas, J. H., Murphy, M. R. Strength-Duration Curve for an Electrically Excitable Tissue Extended Down to Near 1 Nanosecond. IEEE T Plasma Sci 32, 1587-1599 (2004). [Crossref]
37. Zupanic, A., Ribaric, S., Miklavcic, D. Increasing the repetition frequency of electric pulse delivery reduces unpleasant sensations that occur in electrochemotherapy. Neoplasma 54, 246-250 (2007).
38. Ferraro, B., Heller, L. C., Cruz, Y. L., Guo, S., Donate, A., Heller, R. Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a multielectrode array. Gene Ther 18, 496-500 (2011). [Crossref]
39. Sersa, G., Stabuc, B., Cemazar, M., Miklavcic, D., Rudolf, Z. Electrochemotherapy with Cisplatin: Clinical Experience in Malignant Melanoma Patients. Clinical Cancer Research 6, 863-867 (2000).
40. Rodriguez-Cuevas, S., Barroso-Bravo, S., Almanza-Estrada, J., Cristobal-Martinez, L., Gonzalez-Rodriguez, E. Electrochemotherapy in Primary and Metastatic Skin Tumors: Phase II Trial Using Intralesional Bleomycin. Archives of Medical Research 32, 273-276 (2000). [Crossref]
41. Heller, R., Jaroszeski, M. J., Glass, L. F., Messina, J. L., Rapaport, D. P., DeConti, R. C., Fenske, N. A., Gilbert, R. A., Mir, L. M., Reintgen, D. S. Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy. Cancer 77, 964-971 (1996). [Crossref]
42. Zupanic, A., Miklavcic, D. in Irreversible Electroporation (Ed. B. Rubinsky) 203-222 (Springer, 2010).
43. Golberg, A., Rubinsky, B. A statistical model for multidimensional irreversible electroporation cell death in tissue. BioMedical Engineering OnLine 9:13, doi:10.1186/1475-1925X-1189-1113 (2010). [Crossref]
44. Sersa, G., Miklavcic, D., Cemazar, M., Rudolf, Z., Pucihar, G., Snoj, M. Electrochemotherapy in treatment of tumours. EJSO 34, 232-240 (2008). [Crossref]
45. Miklavcic, D., Corovic, S., Pucihar, G., Pavselj, N. Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. EJC Supplements, 45-51 (2006). [Crossref]
46. Miklavcic, D., Semrov, D., Mekid, H., Mir, L. M. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim. Biophys. Acta 1523 73-83 (2000). [Crossref]
47. Miklavcic, D., Snoj, M., Zupanic, A., Kos, B., Cemazar, M., Kropivnik, M., Bracko, M., Pecnik, E., Gadzijev, E., Sersa, G. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomedical Engineering Online 9 (2010). [Crossref]
48. Sten-Knudsen, O. The ineffectiveness of the ‘window field’ in the initiation of muscle contraction. J Physiol 125, 396-404 (1954).
49. Reilly, J. P. Applied Bioelectricity: From Electrical Stimulation to Electropathology (Springler, 1998).
50. Pavselj, N., Miklavcic, D. Numerical modeling in electroporation-based biomedical applications. Radiology and Oncology 42, 159-168 (2008).
51. Weaver, J. C. Electroporation of cells and tissues. IEEE Transactions on Plasma Science 28, 24-33 (2000). [Crossref]
52. Ivorra, A., Al-Sakere, B., Rubinsky, B., Mir, L. M. In vivo electrical conductivity measurements during and after tumor electroporation: conductivity changes reflect the treatment outcome. Physics in Medicine and Biology 54, 5949 (2009). [Crossref]
53. Pavselj, N., Bregar, Z., Cukjati, D., Batiuskaite, D., Mir, L. M., Miklavcic, D. The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals. Biomedical Engineering, IEEE Transactions on 52, 1373-1381 (2005). [Crossref]
54. Kos, B., Zupanic, A., Kotnik, T., Snoj, M., Sersa, G., Miklavcic, D. Robustness of Treatment Planning for Electrochemotherapy of Deep-Seated Tumors. Journal of Membrane Biology 236, 147-153 (2010). [Crossref]
55. Daniels, C., Rubinsky, B. Electrical Field and Temperature Model of Nonthermal Irreversible Electroporation in Heterogeneous Tissues. Journal of Biomechanical Engineering 131, 071006-071012 (2009). [Crossref]
56. NanoKnife® System, http://www.angiodynamics.com/products/nanoknife. 57. Gothelf, A., Gehl, J. Gene Electrotransfer to Skin; Review of Existing Literature and Clinical Perspectives. Current Gene Therapy 10, 287-299 (2010). [Crossref]
58. Denet, A.-R., Vanbever, R., Preat, V. Skin electroporation for transdermal and topical delivery. Advanced Drug Delivery Reviews 56, 659-674 (2004). [Crossref]
59. Pavselj, N., Miklavcic, D. Numerical Models of Skin Electropermeabilization Taking Into Account Conductivity Changes and the Presence of Local Transport Regions. IEEE Transactions on Plasma Science 36, 1650-1658 (2008). [Crossref]
60. Dosdall, D. J., Fast, V. G., Ideker, R. E. Mechanisms of Defibrillation. Annu Rev Biomed Eng 12, 233-258 (2010).
61. Joshi, R. P. Modeling Electrode-Based Stimulation of Muscle and Nerve by Ultrashort Electric Pulses. IEEE T Plasma Sci 32, 1687-1695 (2004). [Crossref]
62. Rassier, D. E. Muscle Biophysics. From Molecules to Cells (Springler, 2010).
63. Pumir, A., Romey, G., Krinsky, V. Deexcitation of Cardiac Cells. Biophys J 74, 2850-2861 (1998).
64. Rayment, I., Holden, H. M., Whittaker, M., Yohn, C. B., Lorenz, M., Holmes, K. C., Milligan, R. A. Structure of the actin-myosin complex and its implications for muscle contraction. Science 261, 58-65 (1993).
65. Joshi, R. P., Mishra, A., Song, J., Pakhomov, A. G., Schoenbach, K. H. Simulation studies of ultrashort, high-intensity electric pulse induced action potential block in whole-animal nerves. IEEE Trans Biomed Engr 55, 1391-1398 (2008). [Crossref]
66. Pakhomov, A., Kolb, J. F., Joshi, R. P., Schoenbach, K. H., Dayton, T., Comeaux, J., Ashmore, J., Beason, C. Neuromuscular disruption with ultrashort electrical pulses. Proc SPIE-Int Soc Opt Eng 6219, 621903-621910 (2006). [Crossref]
67. Delitto, A., Strube, M. J., Shulman, A. D., Minor, S. D. A Study of Discomfort with Electrical Stimulation. Physical Therapy 72, 410-421 (1992).
68. Horowicz, P., Schneider, M. F. Membrane charge moved at contraction thresholds in skeletal muscle fibres. J Physiol 314, 595-633 (1981).
69. Pakhomova, O. N., Gregory, B. W., Khorokhorina, V. A., Bowman, A. M., Xiao, S., Pakhomov, A. Electroporation-Induced Electrosensitization. PLoS ONE 6, e17100 . doi:17110.11371/journal.pone.0017100 (2011). [Crossref]
70. Krastev, P., Tracey, B. in Proceedings of the COMSOL Conference.
71. Martinek, J., Stickler, Y., Reichel, M., Rattay, F. in Proceedings of the COMSOL Conference.
72. Long, G. L., Plescia, D., Shires, P. K. in Proceedings of the COMSOL Conference (Comsol).
73. Reichel, M., Mayr, W., Rattay, F. Computer simulation of field distribution and excitation of denervated muscle fibers caused by surface electrodes. Artificial Organs 23, 453-456 (1999). [Crossref]
74. Jayanti, V., Zviman, M. M., Nazarian, S., Halperin, H. R., Berger, R. D. Novel electrode design for potentially painless internal defibrillation also allows for successful external defibrillation. J Cardiovasc Electrophysiol. 18, 1095-1100 (2007). [Crossref]
75. Jayam, V., Zviman, M., Jayanti, V., Roguin, A., Halperin, H., Berger, R. D. Internal defibrillation with minimal skeletal muscle activation: a new paradigm toward painless defibrillation. Heart Rhythm 2, 1114-1115 (2005). [Crossref]
76. Choi, S.-O., Kim, Y., Park, J.-H., Hutcheson, J., Gill, H., Yoon, Y.-K., Prausnitz, M., Allen, M. An electrically active microneedle array for electroporation. Biomedical Microdevices 12, 263-273 (2011). [Crossref]
77. Spugnini, E. P., Citro, G., Porrello, A. Rational design of new electrodes for electrochemotherapy. Journal of Experimental & Clinical Cancer Research 24, 246-254 (2005).
78. Zupanic, A., Corovic, S., Miklavcic, D. Optimization of electrode position and electric pulse amplitude in electrochemotherapy. Radiology and Oncology 42, 93-101 (2008). [Crossref]
79. Zupanic, A., Corovic, S., Miklavcic, D., Pavlin, M. Numerical optimization of gene electrotransfer into muscle tissue. Biomedical Engineering online 9:66, doi:10.1186/1475-1925X-1189-1166 (2010). [Crossref]
80. Edd, J. F., Davalos, R. Mathematical Modeling of Irreversible Electroporation for Treatment Planning. Technology in cancer research & treatment 6, 275-286 (2007).
81. Reilly, J. Peripheral nerve stimulation by induced electric currents: Exposure to time-varying magnetic fields. Medical and Biological Engineering and Computing 27, 101-110 (1989).
82. Corovic, S., Zupanic, A., Kranjc, S., Al Sakere, B., Leroy-Willig, A., Mir, L., Miklavcic, D. The influence of skeletal muscle anisotropy on electroporation: in vivo study and numerical modeling. Medical and Biological Engineering and Computing 48, 637-648 (2010). [Crossref]

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Received: October 20, 2011; Revised: December 7, 2011; Accepted: December 20, 2011

TCRT April 2012

category image
Volume 11
No.2 (105-201)
April 2012
ISSN 1533-0338

DOI: 10.7785/tcrt.2012.500249

Alex Golberg, Ph.D.*
Boris Rubinsky, Ph.D.

Department of Mechanical Engineering, Etcheverry Hall, 6124, University of California at Berkeley, Berkeley, CA 94720, USA

*Corresponding author: Alex Golberg, Ph.D.
E-mail: alex.golberg@berkeley.edu