Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE)

Open access


Background. Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.

Materials and methods. The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy.

Results. Output of the numerical treatment planning method shows that a 19.9 cm3 irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months.

Conclusions. Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

1 Davalos R, Mir L, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng 2005; 33: 223-31.

2 Yarmush ML, Golberg A, Serša G, Kotnik T, Miklavčič D. Electroporation-based technologies for medicine: principles, applications, and challenges. Annu Rev Biomed Eng 2014; 16: 295-320.

3 Jiang C, Davalos R, Bischof J. A review of basic to clinical studies of irreversible electroporation therapy. IEEE Trans Biomed Eng 2015; 62: 4-20.

4 Martin RCG. Irreversible electroporation of locally advanced pancreatic head adenocarcinoma. J Gastrointest Surg 2013; 17: 1850-6.

5 Scheffer HJ, Melenhorst MCAM, Vogel JA, van Tilborg AAJM, Nielsen K, Kazemier G, et al. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report. Cardiovasc Intervent Radiol 2015; 38: 760–5.

6 Qin Z, Jiang J, Long G, Lindgren B, Bischof JC. Irreversible electroporation: an in vivo study with dorsal skin fold chamber. Ann Biomed Eng 2013; 41: 619-29.

7 Neal RE, Garcia PA, Kavnoudias H, Rosenfeldt F, Mclean CA, Earl V, et al. In vivo irreversible electroporation kidney ablation: experimentally correlated numerical models. IEEE Trans Biomed Eng 2015; 62: 561-9.

8 Arena CB, Mahajan RL, Nichole Rylander M, Davalos RV. An experimental and numerical investigation of phase change electrodes for therapeutic irreversible electroporation. J Biomech Eng 2013; 135: 111009.

9 Garcia PA, Rossmeisl JH Jr, Neal RE 2nd, Ellis TL, Davalos RV. A parametric study delineating irreversible electroporation from thermal damage based on a minimally invasive intracranial procedure. Biomed Eng Online 2011; 10: 34.

10 Haemmerich D, Wood BJ. Hepatic radiofrequency ablation at low frequencies preferentially heats tumour tissue. Int J Hyperth 2006; 22: 563-74.

11 Pillai K, Akhter J, Chua TC, Shehata M, Alzahrani N, Al-Alem I, et al. Heat sink effect on tumor ablation characteristics as observed in monopolar radiofrequency, bipolar radiofrequency, and microwave, using ex vivo calf liver model. Medicine 2015; 94: e580.

12 Poulou LS, Botsa E, Thanou I, Ziakas PD, Thanos L. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Hepatol 2015; 7: 1054-63.

13 Golberg A, Bruinsma BG, Uygun BE, Yarmush ML. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by «electric field sinks». Sci Rep 2015; 5: 8485.

14 Marcan M, Pavliha D, Music MM, Fuckan I, Magjarevic R, Miklavcic D. Segmentation of hepatic vessels from MRI images for planning of electroporation-based treatments in the liver. Radiol Oncol 2014; 48: 267-81.

15 Marčan M, Kos B, Miklavčič D. Effect of blood vessel segmentation on the outcome of electroporation-based treatments of liver tumors. PloS One 2015; 10: e0125591.

16 Haemmerich D, Schutt D, Wright A, Webster J, Mahvi D. Electrical conductivity measurement of excised human metastatic liver tumours before and after thermal ablation. Physiol Meas 2009; 30: 459-66.

17 Cukjati D, Batiuskaite D, Andre F, Miklavcic D, Mir L. Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry 2007; 70: 501-7.

18 Corovic S, Lackovic I, Sustaric P, Sustar T, Rodic T, Miklavcic D. Modeling of electric field distribution in tissues during electroporation. Biomed Eng OnLine 2013; 12: 16.

19 Hasgall P, Neufeld E, Gosselin M, Klingenböck A, Kuster N. IT’IS Database for thermal and electromagnetic parameters of biological tissues. 2011. Available at Accessed 15 March 2015.

20 Henriques FC. Studies of thermal injury; the predictability and the significance of thermally induced rate processes leading to irreversible epidermal injury. Arch Pathol 1947; 43: 489-502.

21 Sel D, Cukjati D, Batiuskaite D, Slivnik T, Mir LM, Miklavcic D. Sequential finite element model of tissue electropermeabilization. IEEE Trans Biomed Eng 2005; 52: 816-27.

22 Aström M, Zrinzo LU, Tisch S, Tripoliti E, Hariz MI, Wårdell K. Method for patient-specific finite element modeling and simulation of deep brain stimulation. Med Biol Eng Comput 2009; 47: 21-8.

23 Županič A, Kos B, Miklavcic D. Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation. Phys Med Biol 2012; 57: 5425-40.

24 Daniels C, Rubinsky B. Electrical field and temperature model of nonthermal irreversible electroporation in heterogeneous tissues. J Biomech Eng-Trans ASME 2009; 131: 071006.

25 Lee YJ, Lu DSK, Osuagwu F, Lassman C. Irreversible electroporation in porcine liver: short- and long-term effect on the hepatic veins and adjacent tissue by CT with pathological correlation. Invest Radiol 2012; 47: 671-5.

26 Pavliha D, Mušič MM, Serša G, Miklavčič D. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images. PloS One 2013; 8: e69068.

27 Miklavcic D, Snoj M, Zupanic A, Kos B, Cemazar M, Kropivnik M, et al. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomed Eng Online 2010; 9: 10.

28 Long G, Bakos G, Shires PK, Gritter L, Crissman JW, Harris JL, et al. Histological and finite element analysis of cell death due to irreversible electroporation. Technol Cancer Res Treat 2014; 13: 561-9.

29 Zhang Y, White SB, Nicolai JR, Zhang Z, West DL, Kim D, et al. Multimodality imaging to assess immediate response to irreversible electroporation in a rat liver tumor model. Radiology 2014; 271: 721-9.

30 Scheffer HJ, Nielsen K, de Jong MC, van Tilborg AAJM, Vieveen JM, Bouwman A (R. A), et al. Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. J Vasc Interv Radiol 2014; 25: 997-1011.

31 Wagstaff PGK, de Bruin DM, van den Bos W, Ingels A, van Gemert MJC, Zondervan PJ, et al. Irreversible electroporation of the porcine kidney: Temperature development and distribution. Urol Oncol 2015; 33: 168. e1–168.e7.

32 Dollinger M, Jung E-M, Beyer L, Niessen C, Scheer F, Müller-Wille R, et al. Irreversible electroporation ablation of malignant hepatic tumors: subacute and follow-up CT appearance of ablation zones. J Vasc Interv Radiol 2014; 25: 1589-94.

33 Meir A, Hjouj M, Rubinsky L, Rubinsky B. Magnetic resonance imaging of electrolysis. Sci Rep 2015; 5: 8095.

34 Pucihar G, Krmelj J, Reberšek M, Napotnik TB, Miklavčič D. Equivalent pulse parameters for electroporation. IEEE Trans Biomed Eng 2011; 58: 3279-88.

35 Garcia PA, Pancotto T, Rossmeisl JH, Henao-Guerrero N, Gustafson NR, Daniel GB, et al. Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol Cancer Res Treat 2011; 10: 73-83.

36 Miklavčič D, Serša G, Brecelj E, Gehl J, Soden D, Bianchi G, et al. Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med Biol Eng Comput 2012; 50: 1213-25.

37 Kranjc M, Markelc B, Bajd F, Čemažar M, Serša I, Blagus T, et al. In Situ Monitoring of electric field distribution in mouse tumor during electroporation. Radiology 2015; 274: 115-23.

38 Garcia PA, Davalos RV, Miklavcic D. A numerical investigation of the electric and thermal cell kill distributions in electroporation-based therapies in tissue. PloS One 2014; 9: e103083.

Radiology and Oncology

The Journal of Association of Radiology and Oncology

Journal Information

IMPACT FACTOR 2017: 1.722
5-year IMPACT FACTOR: 1.729

CiteScore 2017: 1.84

SCImago Journal Rank (SJR) 2017: 0.574
Source Normalized Impact per Paper (SNIP) 2017: 0.814

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 123 123 40
PDF Downloads 21 21 4