In situ monitoring of electric field distribution in mouse tumor during electroporation.

PURPOSE To investigate the feasibility of magnetic resonance (MR) electric impedance tomography ( EIT electric impedance tomography ) 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 electric impedance tomography 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 electric impedance tomography 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 electric impedance tomography (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 electric impedance tomography can be used for determining electric field distribution in situ during electroporation of tissue. Implementation of MR EIT electric impedance tomography 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.

[1]  L. Mir,et al.  Introduction of definite amounts of nonpermeant molecules into living cells after electropermeabilization: direct access to the cytosol. , 1988, Experimental cell research.

[2]  M. Joy,et al.  In vivo detection of applied electric currents by magnetic resonance imaging. , 1989, Magnetic resonance imaging.

[3]  I. Serša,et al.  Magnetic Resonance Microscopy of Electric Currents , 1994 .

[4]  D Miklavcic,et al.  The importance of electric field distribution for effective in vivo electroporation of tissues. , 1998, Biophysical journal.

[5]  Ohin Kwon,et al.  Magnetic resonance electrical impedance tomography (MREIT): simulation study of J-substitution algorithm , 2002, IEEE Transactions on Biomedical Engineering.

[6]  M. Bureau,et al.  In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle , 2005, Gene Therapy.

[7]  Damijan Miklavcic,et al.  The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals , 2005, IEEE Transactions on Biomedical Engineering.

[8]  Damijan Miklavčič,et al.  Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy , 2006 .

[9]  Ozlem Birgul,et al.  In vivo MRI electrical impedance tomography (MREIT) of tumors. , 2006, Technology in cancer research & treatment.

[10]  Damijan Miklavčič,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 , 2006 .

[11]  Damijan Miklavcic,et al.  Real time electroporation control for accurate and safe in vivo non-viral gene therapy. , 2007, Bioelectrochemistry.

[12]  Igor Sersa,et al.  Auxiliary phase encoding in multi spin-echo sequences: application to rapid current density imaging. , 2008, Journal of magnetic resonance.

[13]  Eung Je Woo,et al.  In Vivo High-ResolutionConductivity Imaging of the Human Leg Using MREIT: The First Human Experiment , 2009, IEEE Transactions on Medical Imaging.

[14]  Boris Rubinsky,et al.  In vivo imaging of irreversible electroporation by means of electrical impedance tomography , 2009, Physics in medicine and biology.

[15]  Zheng Wang,et al.  Conductivity Image Reconstruction of Oblique Slice With C-Shaped Open Permanent Magnet MRI Systems , 2010, IEEE Transactions on Applied Superconductivity.

[16]  Boris Rubinsky,et al.  Magnetic Resonance Imaging Characteristics of Nonthermal Irreversible Electroporation in Vegetable Tissue , 2010, The Journal of Membrane Biology.

[17]  Stephen T Kee,et al.  Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation. , 2010, Radiology.

[18]  Damijan Miklavcic,et al.  Robustness of Treatment Planning for Electrochemotherapy of Deep-Seated Tumors , 2010, The Journal of Membrane Biology.

[19]  Yang Guo,et al.  Irreversible electroporation in the liver: contrast-enhanced inversion-recovery MR imaging approaches to differentiate reversibly electroporated penumbra from irreversibly electroporated ablation zones. , 2011, Radiology.

[20]  Damijan Miklavcic,et al.  Magnetic Resonance Electrical Impedance Tomography for Monitoring Electric Field Distribution During Tissue Electroporation , 2011, IEEE Transactions on Medical Imaging.

[21]  Rafael V. Davalos,et al.  Successful treatment of a large soft tissue sarcoma with irreversible electroporation. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Helle K. Iversen,et al.  Diffusion-Weighted MRI for Verification of Electroporation-Based Treatments , 2011, The Journal of Membrane Biology.

[23]  P. Shires,et al.  Real-time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis. , 2012, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[24]  John C. Bischof,et al.  Irreversible Electroporation: An In Vivo Study with Dorsal Skin Fold Chamber , 2012, Annals of Biomedical Engineering.

[25]  Damijan Miklavcic,et al.  Ex Vivo and In Silico Feasibility Study of Monitoring Electric Field Distribution in Tissue during Electroporation Based Treatments , 2012, PloS one.

[26]  S. Hulley,et al.  Designing clinical research , 2013 .

[27]  Damijan Miklavčič,et al.  Electrochemotherapy: from the drawing board into medical practice , 2014, BioMedical Engineering OnLine.

[28]  Damijan Miklavčič,et al.  Electroporation-based technologies for medicine: principles, applications, and challenges. , 2014, Annual review of biomedical engineering.

[29]  Eung Je Woo,et al.  Electrical Tissue Property Imaging at Low Frequency Using MREIT , 2014, IEEE Transactions on Biomedical Engineering.