Research Papers

The Effect of Small Intestine Heterogeneity on Irreversible Electroporation Treatment Planning

[+] Author and Article Information
Mary Phillips

Quinnipiac University,
275 Mount Carmel Avenue,
Hamden, CT 064518
e-mail: Mary.Phillips@quinnipiac.edu

Manuscript received February 19, 2014; final manuscript received June 2, 2014; accepted manuscript posted June 9, 2014; published online July 16, 2014. Assoc. Editor: Ram Devireddy.

J Biomech Eng 136(9), 091009 (Jul 16, 2014) (11 pages) Paper No: BIO-14-1086; doi: 10.1115/1.4027815 History: Received February 19, 2014; Revised June 02, 2014; Accepted June 09, 2014

Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning.

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Fig. 1

Comsol model of the small intestine geometry. Here, only the right side of the small intestine is modeled, taking advantage of the small intestine symmetry. The small intestine is pressed between two parallel electrodes (9.4 mm wide by 15.6 mm in height), and the different intestinal layers are shown to scale. The red dots mark specific locations on the small intestine model geometry where the local electric field magnitudes and thermal effects were further examined.

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Fig. 2

Directional dependence of electric conductivity in the muscle layers. The muscle fibers in the outer, longitudinal muscle layer are all oriented perpendicular to the electric field, whereas the orientation of muscle fibers in the circumferential muscle layer changes along the circumference of the small intestine.

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Fig. 3

The effect of IRE on the small intestine. (a) The untreated control shows a typical, healthy small intestine. (b) One day after IRE-treatment, the small intestine shows complete cellular ablation. (c) At 7 days after applying IRE, the distinct structure of the small intestine is seen. ((d)–(i)) IRE tissue 3 days after applying the IRE protocol. (d) Areas seen 3 days after treatment still depict a loss in the structural layers of the cells. (e) A very clear boundary is seen between the treated and untreated regions of the longitudinal muscle layer. ((e) and (f)) The boundary between a treated and untreated region is shown. (g) The outer layer of the intestine reveals the presence of blood vascular networks, fibroblasts, macrophages, and neutrophils. (h) The boundary between the treated and untreated zones is seen, focusing on the longitudinal and circumferential muscle layers. (i) Immature epithelial cells are observed lining the lumen at the end of the NTIRE-treated zone. (j) The small intestine is beginning to regain its cellular structure 7 days after IRE-treatment and the mucosa has regenerated, as indicated by the presence of new villi lined with epithelial cells. (k) Masson trichrome staining of an untreated control. (l) 1 day after IRE-treatment the extracellular matrix remains intact. Masson's trichrome staining depicts collagen fibers that are similar in morphology after NTIRE treatment when compared to the control.

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Fig. 4

Electric field dependence on the tissue layers' electrical conductivity in the submucosa at location (0 mm, 0.39 mm) for (a) static electrical conductivity values for each tissue domain and (b) dynamic (electric field dependent) electrical conductivity values. The lines on each plot represent the variation of σ2 from 0.1 to 0.8 S/m in increasing order by increments of 0.1 S/m.

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Fig. 5

Electric field distribution and ablated tissue volume varies greatly, depending on electrical conductivity of each tissue layer. Results obtained used the heterogeneous static electrical conductivity model. Uncolored sections are representative of regions where the electric field did not surpass the threshold of 500 V/cm and thus are considered to have not undergone IRE ablation.

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Fig. 6

The electric conductivity and electric field distribution are compared for the static electrical conductivity model ((a) and (c)) and the dynamic electrical conductivity model ((b) and (d)) for when σ1 = 0.8, σ2 = 0.1, and σ3 = 0.8. As can be seen in comparing (a) and (b), the electrical conductivity distribution changes due to the electric field for the dynamic electrical conductivity model. (e) The electric field distribution is shown for the dynamic electrical conductivity case when σ1 = 0.3, σ2 = 0.6, and σ3 = 0.8 with an ablation threshold of 500 V/cm and this is compared to the same electrical conductivity values when the threshold is increased to 600 V/cm (f).



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