In Situ Monitoring of Electric Field Distribution in Mouse Tumor during Electroporation
Abstract
MR electric impedance tomography enables reconstruction of electric field distribution by allowing measurement of the electric current density distribution and electric conductivity of the treated subject during application of electric pulses by using MR imaging and numeric algorithms.
Purpose
To investigate the feasibility of magnetic resonance (MR) electric impedance tomography (EIT) technique for in situ monitoring of electric field distribution during in vivo electroporation of mouse tumors to predict reversibly electroporated tumor areas.
Materials and Methods
All experiments received institutional animal care and use committee approval. Group 1 consisted of eight tumors that were used for determination of predicted area of reversibly electroporated tumor cells with MR EIT by using a 2.35-T MR imager. In addition, T1-weighted images of tumors were acquired to determine entrapment of contrast agent within the reversibly electroporated area. A correlation between predicted reversible electroporated tumor areas as determined with MR EIT and areas of entrapped MR contrast agent was evaluated to verify the accuracy of the prediction. Group 2 consisted of seven tumors that were used for validation of radiologic imaging with histopathologic staining. Histologic analysis results were then compared with predicted reversible electroporated tumor areas from group 1. Results were analyzed with Pearson correlation analysis and one-way analysis of variance.
Results
Mean coverage ± standard deviation of tumors with electric field that leads to reversible electroporation of tumor cells obtained with MR EIT (38% ± 9) and mean fraction of tumors with entrapped MR contrast agent (41% ± 13) were correlated (Pearson analysis, r = 0.956, P = .005) and were not statistically different (analysis of variance, P = .11) from mean fraction of tumors from group 2 with entrapped fluorescent dye (39% ± 12).
Conclusion
MR EIT can be used for determining electric field distribution in situ during electroporation of tissue. Implementation of MR EIT in electroporation-based applications, such as electrochemotherapy and irreversible electroporation tissue ablation, would enable corrective interventions before the end of the procedure and would additionally improve the treatment outcome.
© RSNA, 2014
References
- 1. . Electroporation-based technologies for medicine: principles, applications, and challenges. Annu Rev Biomed Eng 2014;16:295–320. Crossref, Medline, Google Scholar
- 2. . 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 2006;4(11):3–13. Crossref, Google Scholar
- 3. . Electrochemotherapy: from the drawing board into medical practice. Biomed Eng Online 2014;13(1):29. Crossref, Medline, Google Scholar
- 4. . Successful treatment of a large soft tissue sarcoma with irreversible electroporation. J Clin Oncol 2011;29(13):e372–e377. Crossref, Medline, Google Scholar
- 5. . Advanced hepatic ablation technique for cr eating complete cell death: irreversible electroporation. Radiology 2010;255(2):426–433. Link, Google Scholar
- 6. . Magnetic resonance imaging characteristics of nonthermal irreversible electroporation in vegetable tissue. J Membr Biol 2010;236(1):137–146. Crossref, Medline, Google Scholar
- 7. . In vivo imaging of irreversible electroporation by means of electrical impedance tomography. Phys Med Biol 2009;54(16):4927–4943. Crossref, Medline, Google Scholar
- 8. . Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry 2007;70(2):501–507. Crossref, Medline, Google Scholar
- 9. . Diffusion-weighted MRI for verification of electroporation-based treatments. J Membr Biol 2011;240(3):131–138. Crossref, Medline, Google Scholar
- 10. . Irreversible electroporation in the liver: contrast-enhanced inversion-recovery MR imaging approaches to differentiate reversibly electroporated penumbra from irreversibly electroporated ablation zones. Radiology 2011;258(2):461–468. Link, Google Scholar
- 11. . Real-time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis. HPB (Oxford) 2012;14(2):98–102. Crossref, Medline, Google Scholar
- 12. . Intraoperative electrochemotherapy of colorectal liver metastases. J Surg Oncol 2014 Apr 30. [Epub ahead of print] Google Scholar
- 13. . Robustness of treatment planning for electrochemotherapy of deep-seated tumors. J Membr Biol 2010;236(1):147–153. Crossref, Medline, Google Scholar
- 14. . Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. Eur J Cancer Suppl 2006;4(11):45–51. Crossref, Google Scholar
- 15. . The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys J 1998;74(5):2152–2158. Crossref, Medline, Google Scholar
- 16. . Magnetic resonance electrical impedance tomography for monitoring electric field distribution during tissue electroporation. IEEE Trans Med Imaging 2011;30(10):1771–1778. Crossref, Medline, Google Scholar
- 17. . Ex vivo and in silico feasibility study of monitoring electric field distribution in tissue during electroporation based treatments. PLoS One 2012;7(9):e45737. Crossref, Medline, Google Scholar
- 18. . Electrical tissue property imaging at low frequency using MREIT. IEEE Trans Biomed Eng 2014;61(5):1390–1399. Crossref, Medline, Google Scholar
- 19. . In vivo detection of applied electric currents by magnetic resonance imaging. Magn Reson Imaging 1989;7(1):89–94. Crossref, Medline, Google Scholar
- 20. . Magnetic resonance microscopy of electric currents. J Magn Reson A 1994;111(1):93–99. Crossref, Google Scholar
- 21. . Auxiliary phase encoding in multi spin-echo sequences: application to rapid current density imaging. J Magn Reson 2008;190(1):86–94. Crossref, Medline, Google Scholar
- 22. . Magnetic resonance electrical impedance tomography (MREIT): simulation study of J-substitution algorithm. IEEE Trans Biomed Eng 2002;49(2):160–167. Crossref, Medline, Google Scholar
- 23. . In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle. Gene Ther 2005;12(19):1434–1443. Crossref, Medline, Google Scholar
- 24. . Designing clinical research. Philadelphia, Pa: Wolters Kluwer/Lippincott Williams & Wilkins, 2013. Google Scholar
- 25. . In vivo MRI electrical impedance tomography (MREIT) of tumors. Technol Cancer Res Treat 2006;5(4): 381–387. Medline, Google Scholar
- 26. . The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals. IEEE Trans Biomed Eng 2005;52(8):1373–1381. Crossref, Medline, Google Scholar
- 27. . Irreversible electroporation: an in vivo study with dorsal skin fold chamber. Ann Biomed Eng 2013;41(3):619–629. Crossref, Medline, Google Scholar
- 28. . Introduction of definite amounts of nonpermeant molecules into living cells after electropermeabilization: direct access to the cytosol. Exp Cell Res 1988;175(1):15–25. Crossref, Medline, Google Scholar
- 29. . In vivo high-resolution conductivity imaging of the human leg using MREIT: the first human experiment. IEEE Trans Med Imaging 2009;28(11):1681–1687. Crossref, Medline, Google Scholar
- 30. . Conductivity image reconstruction of oblique slice with C-shaped open permanent magnet MRI systems. IEEE Trans Appl Supercond 2010;2 0(3):814–817. Crossref, Google Scholar
Article History
Received February 6, 2014; revision requested April 17; revision received May 26; accepted June 9; final version accepted June 18.Published online: Aug 19 2014
Published in print: Jan 2015