Purpose: To study the effects of the surrounding electrical micro-environment and local tissue parameters on the electrical parameters and outcome of irreversible electroporation (IRE) ablation in porcine muscle, kidney, and liver tissue. Materials and Methods: Animal Care and Use Committee approval was obtained, and National Institutes of Health guidelines were followed. IRE ablation (n = 90) was applied in muscle (n = 44), kidney (n = 28), and liver (n = 18) tissue in 18 pigs. Two electrodes with tip exposure of 1.5-2 cm were used at varying voltages (1500-3000 V), pulse repetitions (n = 70-100), pulse length (70-100 mu sec), and electrode spacing (1.5-2 cm). In muscle tissue, electrodes were placed exactly parallel, in plane, or perpendicular to paraspinal muscle fibers; in kidney tissue, in the cortex or adjacent to the renal medulla; and in liver tissue, with and without metallic or plastic plates placed 1-2 cm from electrodes. Ablation zones were determined at gross pathologic (90-120 minutes after IRE) and immunohistopathologic examination (6 hours after) for apoptosis and heat-shock protein markers. Multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis were used for analysis. Results: Mean (+/- standard deviation) ablation zones in muscle were 6.2 cm +/- 0.3 x 4.2 cm +/- 0.3 for parallel electrodes and 4.2 cm +/- 0.8 x 3.0 cm +/- 0.5 for in-plane application. Perpendicular orientation resulted in a cross-shaped zone. Orientation significantly affected IRE current applied (28.5-31.7A for parallel, 29.5-39.7A for perpendicular; P = .003). For kidney cortex, ovoid zones of 1.5 cm +/- 0.1 x 0.5 cm +/- 0.0 to 2.5 cm +/- 0.1 x 1.3 cm +/- 0.1 were seen. Placement of electrodes less than 5 mm from the medullary pyramids resulted in treatment effect arcing into the collecting system. For liver tissue, symmetric 2.7 cm +/- 0.2 x 1.4 cm +/- 0.3 coagulation areas were seen without the metallic plate but asymmetric coagulation was seen with the metallic plate. Conclusion: IRE treatment zones are sensitive to varying electrical conductivity in tissues. Electrode location, orientation, and heterogeneities in local environment must be considered in planning ablation treatment. (C)RSNA, 2013