0
Research Papers

An Experimental and Numerical Investigation of Phase Change Electrodes for Therapeutic Irreversible Electroporation

[+] Author and Article Information
Christopher B. Arena

Bioelectromechanical Systems Lab,
Virginia Tech-Wake Forest School of Biomedical
Engineering and Sciences,
Virginia Tech, 330 Kelly Hall (MC0298),
Stanger Street,
Blacksburg, VA 24061
e-mail: carena@vt.edu

Roop L. Mahajan

Institute for Critical Technology and
Applied Science (ICTAS),
Virginia Tech Department of
Mechanical Engineering,
Virginia Tech Department of Engineering
Science and Mechanics,
Virginia Tech, 410 H Kelly Hall (MC0298),
Stanger Street,
Blacksburg, VA 24061

Marissa Nichole Rylander

Tissue Engineering Nanotechnology and
Cancer Research Lab,
Virginia Tech-Wake Forest
School of Biomedical Engineering and Sciences,
Virginia Tech Department of
Mechanical Engineering,
Virginia Tech, 335 Kelly Hall (MC0298),
Stanger Street,
Blacksburg, VA 24061

Rafael V. Davalos

Bioelectromechanical Systems Lab,
Virginia Tech-Wake Forest School of
Biomedical Engineering and Sciences,
Virginia Tech, 329 Kelly Hall (MC0298),
Stanger Street,
Blacksburg, VA 24061

1Corresponding author.

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received April 10, 2013; final manuscript received July 30, 2013; accepted manuscript posted September 6, 2013; published online October 3, 2013. Assoc. Editor: Ram Devireddy.

J Biomech Eng 135(11), 111009 (Oct 03, 2013) (9 pages) Paper No: BIO-13-1182; doi: 10.1115/1.4025334 History: Received April 10, 2013; Revised July 30, 2013; Accepted September 06, 2013

Irreversible electroporation (IRE) is a new technology for ablating aberrant tissue that utilizes pulsed electric fields (PEFs) to kill cells by destabilizing their plasma membrane. When treatments are planned correctly, the pulse parameters and location of the electrodes for delivering the pulses are selected to permit destruction of the target tissue without causing thermal damage to the surrounding structures. This allows for the treatment of surgically inoperable masses that are located near major blood vessels and nerves. In select cases of high-dose IRE, where a large ablation volume is desired without increasing the number of electrode insertions, it can become challenging to design a pulse protocol that is inherently nonthermal. To solve this problem we have developed a new electrosurgical device that requires no external equipment or protocol modifications. The design incorporates a phase change material (PCM) into the electrode core that melts during treatment and absorbs heat out of the surrounding tissue. Here, this idea is reduced to practice by testing hollow electrodes filled with gallium on tissue phantoms and monitoring temperature in real time. Additionally, the experimental data generated are used to validate a numerical model of the heat transfer problem, which is then applied to investigate the cooling performance of other classes of PCMs. The results indicate that metallic PCMs, such as gallium, are better suited than organics or salt hydrates for thermal management, because their comparatively higher thermal conductivity aids in heat dissipation. However, the melting point of the metallic PCM must be properly adjusted to ensure that the phase transition is not completed before the end of treatment. When translated clinically, phase change electrodes have the potential to continue to allow IRE to be performed safely near critical structures, even in high-dose cases.

FIGURES IN THIS ARTICLE
<>
Copyright © 2013 by ASME
Your Session has timed out. Please sign back in to continue.

References

Okino, M., and Mohri, H., 1987, “Effects of a High-Voltage Electrical Impulse and an Anticancer Drug on in Vivo Growing Tumors,” Jpn. J. Cancer Res., 78(12), pp. 1319–1321. [PubMed]
Titomirov, A. V., Sukharev, S., and Kistanova, E., 1991, “In Vivo Electroporation and Stable Transformation of Skin Cells of Newborn Mice by Plasmid DNA,” Biochim. Biophys. Acta, 1088(1), pp. 131–134. [CrossRef] [PubMed]
Neumann, E., Schaeferridder, M., Wang, Y., and Hofschneider, P. H., 1982, “Gene Transfer into Mouse Lyoma Cells by Electroporation in High Electric Fields,” Embo. J., 1(7), pp. 841–845. [PubMed]
Davalos, R. V., Mir, L. M., and Rubinsky, B., 2005, “Tissue Ablation With Irreversible Electroporation,” Ann. Biomed. Eng., 33(2), pp. 223–231. [CrossRef] [PubMed]
Pavliha, D., Kos, B., Zupanic, A., Marcan, M., Sersa, G., and Miklavcic, D., 2012, “Patient-Specific Treatment Planning of Electrochemotherapy: Procedure Design and Possible Pitfalls,” Bioelectrochemistry, 87, pp. 265–273. [CrossRef] [PubMed]
Garcia, P. A., Pancotto, T., Rossmeisl, J. H., Henao-Guerrero, N., Gustafson, N. R., Daniel, G. B., Robertson, J. L., Ellis, T. L., and Davalos, R. V., 2011, “Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine Patient,” Technol. Cancer Res. Treat., 10(1), pp. 73–83. [PubMed]
Neal, R. E.2nd, Rossmeisl, J. H.Jr., Garcia, P. A., Lanz, O. I., Henao-Guerrero, N., and Davalos, R. V., 2011, “Successful Treatment of a Large Soft Tissue Sarcoma With Irreversible Electroporation,” J. Clin. Oncol. 29(13), pp. e372–e377. [CrossRef] [PubMed]
Weaver, J. C., and Chizmadzhev, Y. A., 1996, “Theory of Electroporation: A Review,” Bioelectrochem. Bioenergy, 41(2), pp. 135–160. [CrossRef]
Mir, L. M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek, J.Jr., Schwaab, G., Luboinski, B., and Paoletti, C., 1991, “Electrochemotherapy, A New Antitumor Treatment: First Clinical Trial,” C. R. Acad. Sci. III, 313(13), pp. 613–618. [PubMed]
Daud, A. I., DeConti, R. C., Andrews, S., Urbas, P., Riker, A. I., Sondak, V. K., Munster, P. N., Sullivan, D. M., Ugen, K. E., Messina, J. L., and Heller, R., 2008, “Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma,” J. Clin. Oncol., 26(36), pp. 5896–5903. [CrossRef] [PubMed]
Thomson, K. R., Cheung, W., Ellis, S. J., Park, D., Kavnoudias, H., Loader-Oliver, D., Roberts, S., Evans, P., Ball, C., and Haydon, A., 2011, “Investigation of the Safety of Irreversible Electroporation in Humans,” J. Vasc. Interv. Radiol., 22(5), pp. 611–621. [CrossRef] [PubMed]
Gehl, J., 2003, “Electroporation: Theory and Methods, Perspectives for Drug Delivery, Gene Therapy and Research,” Acta Physiol. Scand., 177(4), pp. 437–447. [CrossRef] [PubMed]
Li, W., Fan, Q. Y., Ji, Z. W., Qiu, X. C., and Li, Z., 2011, “The Effects of Irreversible Electroporation (IRE) on Nerves,” Plos One, 6(4), p. e18831. [CrossRef] [PubMed]
Maor, E., Ivorra, A., Leor, J., and Rubinsky, B., 2007, “The Effect of Irreversible Electroporation on Blood Vessels,” Technol. Cancer Res. Treat., 6(4), pp. 307–312. [PubMed]
Rubinsky, B., Onik, G., and Mikus, P., 2007, “Irreversible Electroporation: A New Ablation Modality—Clinical Implications,” Technol. Cancer Res. Treat., 6(1), pp. 37–48. [PubMed]
Appelbaum, L., Ben-David, E., Sosna, J., Nissenbaum, Y., and Goldberg, S. N., 2012, “US Findings After Irreversible Electroporation Ablation: Radiologic-Pathologic Correlation,” Radiology, 262(1), pp. 117–125. [CrossRef] [PubMed]
Becker, S. M., and Kuznetsov, A. V., 2007, “Thermal Damage Reduction Associated With in Vivo Skin Electroporation: A Numerical Investigation Justifying Aggressive Pre-Cooling,” Int. J. Heat Mass Transfer, 50, pp. 105–116. [CrossRef]
Arena, C. B., Mahajan, R. L., Rylander, M. N., and Davalos, R. V., 2012, “Towards the Development of Latent Heat Storage Electrodes for Electroporation-Based Therapies,” Appl. Phys. Lett., 101(8), p. 083902. [CrossRef]
Mondieig, D., Rajabalee, F., Laprie, A., Oonk, H. A. J., Calvet, T., and Cuevas-Diarte, M. A., 2003, “Protection of Temperature Sensitive Biomedical Products Using Molecular Alloys As Phase Change Material,” Transfus Apher Sci., 28(2), pp. 143–148. [CrossRef] [PubMed]
Shim, H., McCullough, E. A.,and Jones, B. W., 2001, “Using Phase Change Materials in Clothing,” Textile Res. J., 71(6), pp. 495–502. [CrossRef]
Sheeran, P. S., and Dayton, P. A., 2012, “Phase-Change Contrast Agents for Imaging and Therapy,” Curr. Pharm. Design, 18(15), pp. 2152–2165. [CrossRef]
Sheeran, P. S., Luois, S. H., Mullin, L. B., Matsunaga, T. O., and Dayton, P. A., 2012, “Design of Ultrasonically-Activatable Nanoparticles Using Low Boiling Point Perfluorocarbons,” Biomaterials, 33(11), pp. 3262–3269. [CrossRef] [PubMed]
Marongiu, M. J., and Clarksean, R., 1997, “Thermal Management of Electronics Enclosures Under Unsteady Heating/Cooling Conditions Using Phase Change Materials (PCM),” Proceedings of the 32nd Intersociety Energy Conversion Engineering Conference (IECEC), pp. 1865–1870.
Ge, H., and Liu, J., 2012, “Phase Change Effect of Low Melting Point Metal for an Automatic Cooling of USB Flash Memory,” Front. Energy, 6(3), pp. 207–209. [CrossRef]
Prakash, J., Garg, H. P., and Datta, G., 1985, “A Solar Water Heater With a Built-in Latent-Heat Storage,” Energy Convers. Manage., 25(1), pp. 51–56. [CrossRef]
Benard, C., Body, Y., and Zanoli, A., 1985, “Experimental Comparison of Latent and Sensible Heat Thermal Walls,” Solar Energy, 34(6), pp. 475–487. [CrossRef]
Etheridge, M. L., Choi, J., Ramadhyani, S., and Bischof, J. C., 2013, “Methods for Characterizing Convective Cryoprobe Heat Transfer in Ultrasound Gel Phantoms,” ASME J. Biomech. Eng., 135(2), p. 021001. [CrossRef]
Wagner, G. H., and Gitzen, W. H., 1952, “Gallium,” J. Chem. Educ., 29(4), p. 162. [CrossRef]
Krishnan, S., and Garimella, S. V., 2004, “Analysis of a Phase Change Energy Storage System for Pulsed Power Dissipation,” IEEE Trans. Compon. Pack Technol., 27(1), pp. 191–199. [CrossRef]
Dantzig, J. A., 1989, “Modeling Liquid-Solid Phase Changes With Melt Convection,” Int. J. Numer. Methods Eng., 28(8), pp. 1769–1785. [CrossRef]
Garcia, P. A., Davalos, R. V., and Pearce, J. A., 2012, “A Comparison Between the Pulsed and Duty Cycle Approaches Used to Capture the Thermal Response of Tissue During Electroporation-Based Therapies,” ASME Summer Bioengineering Conference Fajardo, Puerto Rico, p. 80574.
Deri, B., Kotovsky, J., and Spadaccini, C., 2010, “Assessment of Latent Heat Reservoirs for Thermal Management of QCW Laser Diodes,” No. LLNL-TR-425903, Lawrence Livermore National Laboratory, Livermore, CA.
Incropera, F. P., and DeWitt, D. P., 1996, Fundamentals of Heat and Mass Transfer, Wiley, New York.
Amin, D. V., Lozanne, K., Parry, P. V., Engh, J. A., Seelman, K., and Mintz, A., 2011, “Image-Guided Frameless Stereotactic Needle Biopsy in Awake Patients Without the Use of Rigid Head Fixation,” J. Neurosurg., 114(5), pp. 1414–1420. [CrossRef] [PubMed]
Predel, B., 1960, “Die Zustandsbilder Gallium-Wismut und Gallium-Quecksilber, Vergleich der Koexistenzkurven mit den Theorien der Entmischung,” Z. Phys. Chem., 24(3–4), pp. 206–216. [CrossRef]
Antunes, C. L., Almeida, T. R. O., Raposeiro, N., Goncalves, B., and Almeida, P., 2012, “Using a Tubular Electrode for Radiofrequency Ablation Numerical and Experimental Analysis,” Compel, 31(4), pp. 1077–1086. [CrossRef]
Zalba, B., Marin, J. M., Cabeza, L. F., and Mehling, H., 2003, “Review on Thermal Energy Storage With Phase Change: Materials, Heat Transfer Analysis and Applications,” Appl. Therm. Eng., 23(3), pp. 251–283. [CrossRef]
Garcia, P. A., Rossmeisl, J. H., Neal, R. E., Ellis, T. L., Olson, J. D., Henao-Guerrero, N., Robertson, J., and Davalos, R. V., 2010, “Intracranial Nonthermal Irreversible Electroporation: in Vivo Analysis,” J. Membr. Biol., 236(1), pp. 127–136. [CrossRef] [PubMed]
Arena, C. B., Szot, C. S., Garcia, P. A., Rylander, M. N., and Davalos, R. V., 2012, “A Three-Dimensional In Vitro Tumor Platform for Modeling Therapeutic Irreversible Electroporation,” Biophys. J, 103(9), pp. 2033–2042. [CrossRef] [PubMed]
Faroja, M., Ahmed, M., Appelbaum, L., Ben-David, E., Moussa, M., Sosna, J., Nissenbaum, I., and Goldberg, S. N., 2013, “Irreversible Electroporation Ablation: Is All the Damage Nonthermal?,” Radiology, 266(2), pp. 462–470. [CrossRef] [PubMed]
Ben-David, E., Appelbaum, L., Sosna, J., Nissenbaum, I., and Goldberg, S. N., 2012, “Characterization of Irreversible Electroporation Ablation in in Vivo Porcine Liver,” Am. J. Roentgenol., 198(1), pp. W62–W68. [CrossRef]
Stupar, A., Drofenik, U., and Kolar, J. W., 2010, “Application of Phase Change Materials for Low Duty Cycle High Peak Load Power Supplies,” 6th International Conference on Integrated Power Electronics Systems (CIPS), pp. 1–11.
Lacroix, M., 2001, “Contact Melting of a Phase Change Material Inside a Heated Parallelepedic Capsule,” Energy Convers. Manage., 42(1), pp. 35–47. [CrossRef]
Davalos, R. V., Otten, D. M., Mir, L. M., and Rubinsky, B., 2004, “Electrical Impedance Tomography for Imaging Tissue Electroporation,” IEEE Trans. Biomed. Eng., 51(5), pp. 761–767. [CrossRef] [PubMed]
Garcia, P. A., Rossmeisl, J. H.Jr., Neal, R. E.2nd, Ellis, T. L., and Davalos, R. V., 2011, “A Parametric Study Delineating Irreversible Electroporation From Thermal Damage Based on a Minimally Invasive Intracranial Procedure,” Biomed. Eng. Online, 10(1), p. 34. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

(a) Image of the experimental setup used to monitor temperature during electroporation with phase change electrodes. The electrodes and fiber optic temperature probe are spaced using a printed circuit board, inserted into the tissue phantom, and placed inside an incubator (white arrow). The insert displays the hollow brass electrodes with the inclusion of a gallium core (black arrow). (b) Representative mesh of the finite element model used to simulate the electroporation protocol with 79,198 elements.

Grahic Jump Location
Fig. 2

Comparison of the measured temperatures (dotted lines) with those predicted by the numerical model (solid lines) for solid electrodes (black) and phase change electrodes (gray). The insert displays the volume fraction of solid material predicted by the numerical model at the end of the 99 s pulse protocol. Due to symmetry, only a single electrode is shown with the medial portion on the left.

Grahic Jump Location
Fig. 3

Surface contour plots from the numerical model showing the (a) electric field distribution and temperature distribution for the (b) solid electrodes and (c) phase change electrodes. All plots are shown at the end of the 99 s pulse protocol. In the x-y plane, the cross section is taken at a depth of 1.80 cm from the surface of the ultrasound gel. In the x-z plane the cross section is taken through the center of the electrodes (y = 0).

Grahic Jump Location
Fig. 4

Temperature profiles resulting from the parametric study on electrode radius (0.5, 0.75, 1.0, and 1.25 mm) and PCM melting point above the baseline temperature (1, 4, 7, and 10 °C) for gallium. Temperatures are plotted at the medial electrode–tissue interface at a depth of 1.80 cm from the surface of the ultrasound gel. Dotted lines represent solid electrodes for comparison. In (c) the vertical arrow indicates the end of melting and the horizontal arrow highlights the temperature at the end of treatment.

Grahic Jump Location
Fig. 5

Temperature profiles resulting from the parametric study on electrode radius (0.5, 0.75, 1.0, and 1.25 mm) and PCM melting point above the baseline temperature (1, 4, 7, and 10 °C) when keq/100. Temperatures are plotted at the medial electrode–tissue interface at a depth of 1.80 cm from the surface of the ultrasound gel. Dotted lines represent solid electrodes for comparison. In (c) the vertical arrow indicates the end of melting and the horizontal arrow highlights the temperature at the end of treatment.

Grahic Jump Location
Fig. 6

Comparison of the temperature change during treatment for (a) gallium core electrodes and (b) when keq/100 (b). (c) The difference between (b) and (a) to emphasize the most effective PCM for each parameter combination. White bars represent solid electrodes for comparison.

Grahic Jump Location
Fig. 7

(a) Melting profile for different PCM cores (gallium, keq/10, and keq/100) with a melting point 1 °C above baseline housed within a 1 mm radius electrode. The data is taken at the center of the core at a depth of 1.80 cm from the surface of the ultrasound gel. (b) Cross section of the volume fraction solid material through the center of the electrodes at the end of treatment.

Tables

Errata

Discussions

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In