Computational modeling of internally cooled wet (ICW) electrodes for radiofrequency ablation: Impact of rehydration, thermal convection and electrical conductivity

[EN] Purpose: (1) To analyse rehydration, thermal convection and increased electrical conductivity as the three phenomena which distinguish the performance of internally cooled electrodes (IC) and internally cooled wet (ICW) electrodes during radiofrequency ablation (RFA), (2) Implement a RFA computer model with an ICW which includes these phenomena and (3) Assess their relative influence on the thermal and electrical tissue response and on the coagulation zone size. Methods: A 12-min RFA in liver was modelled using an ICW electrode (17G, 3cm tip) by an impedance-control pulsing protocol with a constant current of 1.5A. A model of an IC electrode was used to compare the ICW electrode performance and the computational results with the experimental results. Results: Rehydration and increased electrical conductivity were responsible for an increase in coagulation zone size and a delay (or absence) in the occurrence of abrupt increases in electrical impedance (roll-off). While the increased electrical conductivity had a remarkable effect on enlarging the coagulation zone (an increase of 0.74cm for differences in electrical conductivity of 0.31S/m), rehydration considerably affected the delay in roll-off, which, in fact, was absent with a sufficiently high rehydration level. In contrast, thermal convection had an insignificant effect for the flow rates considered (0.05 and 1mL/min). Conclusions: Computer results suggest that rehydration and increased electrical conductivity were mainly responsible for the absence of roll-off and increased size of the coagulation zone, respectively, and in combination allow the thermal and electrical performance of ICW electrodes to be modelled during RFA.This work was supported by the Government of Spain through the Spanish Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad under grant number TEC2014-52383-C3-R (TEC2014-52383-C3-1-R).Trujillo Guillen, M.; Bon Corbín, J.; Berjano, E. (2017). Computational modeling of internally cooled wet (ICW) electrodes for radiofrequency ablation: Impact of rehydration, thermal convection and electrical conductivity. International Journal of Hyperthermia. 33(6):624-634. doi:10.1080/02656736.2017.1303751S624634336Kohlhase, K. D., Korkusuz, Y., Gröner, D., Erbelding, C., Happel, C., Luboldt, W., & Grünwald, F. (2016). Bipolar radiofrequency ablation of benign thyroid nodules using a multiple overlapping shot technique in a 3-month follow-up. International Journal of Hyperthermia, 32(5), 511-516. doi:10.3109/02656736.2016.1149234Zhang, F., Wu, G., Sun, H., Ding, J., Xia, F., Li, X., … Bie, P. (2014). Radiofrequency ablation of hepatocellular carcinoma in elderly patients fitting the Milan criteria: A single centre with 13 years experience. International Journal of Hyperthermia, 30(7), 471-479. doi:10.3109/02656736.2014.961042Trujillo, M., Alba, J., & Berjano, E. (2012). Relationship between roll-off occurrence and spatial distribution of dehydrated tissue during RF ablation with cooled electrodes. International Journal of Hyperthermia, 28(1), 62-68. doi:10.3109/02656736.2011.631076McGahan, J. P., & Dodd, G. D. (2001). Radiofrequency Ablation of the Liver. American Journal of Roentgenology, 176(1), 3-16. doi:10.2214/ajr.176.1.1760003Burdío, F., Tobajas, P., Quesada-Diez, R., Berjano, E., Navarro, A., Poves, I., & Grande, L. (2011). Distant Infusion of Saline May Enlarge Coagulation Volume During Radiofrequency Ablation of Liver Tissue Using Cool-tip Electrodes Without Impairing Predictability. American Journal of Roentgenology, 196(6), W837-W843. doi:10.2214/ajr.10.5202Burdío, F., Güemes, A., Burdío, J. M., Navarro, A., Sousa, R., Castiella, T., … Lozano, R. (2003). Bipolar Saline-enhanced Electrode for Radiofrequency Ablation: Results of Experimental Study of in Vivo Porcine Liver. Radiology, 229(2), 447-456. doi:10.1148/radiol.2292020978Lee, J. M., Han, J. K., Kim, S. H., Sohn, K. L., Lee, K. H., Ah, S. K., & Choi, B. I. (2003). A Comparative Experimental Study of the In-vitro Efficiency of Hypertonic Saline-Enhanced Hepatic Bipolar and Monopolar Radiofrequency Ablation. Korean Journal of Radiology, 4(3), 163. doi:10.3348/kjr.2003.4.3.163Goldberg, S. N., Ahmed, M., Gazelle, G. S., Kruskal, J. B., Huertas, J. C., Halpern, E. F., … Lenkinski, R. E. (2001). Radio-Frequency Thermal Ablation with NaCl Solution Injection: Effect of Electrical Conductivity on Tissue Heating and Coagulation—Phantom and Porcine Liver Study. Radiology, 219(1), 157-165. doi:10.1148/radiology.219.1.r01ap27157Lobo, S. M., Afzal, K. S., Ahmed, M., Kruskal, J. B., Lenkinski, R. E., & Goldberg, S. N. (2004). Radiofrequency Ablation: Modeling the Enhanced Temperature Response to Adjuvant NaCl Pretreatment. Radiology, 230(1), 175-182. doi:10.1148/radiol.2301021512Mulier, S., Miao, Y., Mulier, P., Dupas, B., Pereira, P., de Baere, T., … Ni, Y. (2005). Electrodes and multiple electrode systems for radiofrequency ablation: a proposal for updated terminology. European Radiology, 15(4), 798-808. doi:10.1007/s00330-004-2584-xHyoung Kim, J., Nyun Kim, P., Jin Won, H., & Moon Shin, Y. (2013). Percutaneous Radiofrequency Ablation with Internally Cooled versus Internally Cooled Wet Electrodes for Small Subphrenic Hepatocellular Carcinomas. Journal of Vascular and Interventional Radiology, 24(3), 351-356. doi:10.1016/j.jvir.2012.11.025Cha, J., Choi, D., Lee, M. W., Rhim, H., Kim, Y., Lim, H. K., … Park, C. K. (2009). Radiofrequency Ablation Zones in Ex Vivo Bovine and In Vivo Porcine Livers: Comparison of the Use of Internally Cooled Electrodes and Internally Cooled Wet Electrodes. CardioVascular and Interventional Radiology, 32(6), 1235-1240. doi:10.1007/s00270-009-9600-0Lee, J. M., Han, J. K., Chang, J. M., Chung, S. Y., Kim, S. H., Lee, J. Y., … Choi, B. I. (2006). Radiofrequency Ablation of the Porcine Liver In Vivo: Increased Coagulation with an Internally Cooled Perfusion Electrode. Academic Radiology, 13(3), 343-352. doi:10.1016/j.acra.2005.10.020Park, M.-H., Cho, J.-S., Shin, B. S., Jeon, G. S., Lee, B., & Lee, K. (2012). Comparison of Internally Cooled Wet Electrode and Hepatic Vascular Inflow Occlusion Method for Hepatic Radiofrequency Ablation. Gut and Liver, 6(4), 471-475. doi:10.5009/gnl.2012.6.4.471Han, J. K., Lee, J. M., Kim, S. H., Lee, J. Y., Park, H. S., Eo, H., & Choi, B. I. (2005). Radiofrequency ablation in the liver using two cooled-wet electrodes in the bipolar mode. European Radiology, 15(10), 2163-2170. doi:10.1007/s00330-005-2713-1Romero-Méndez, R., Tobajas, P., Burdío, F., Gonzalez, A., Navarro, A., Grande, L., & Berjano, E. (2012). Electrical-thermal performance of a cooled RF applicator for hepatic ablation with additional distant infusion of hypertonic saline:In vivostudy and preliminary computer modeling. International Journal of Hyperthermia, 28(7), 653-662. doi:10.3109/02656736.2012.711894Kim, J. H., Kim, P. N., Won, H. J., & Shin, Y. M. (2012). Percutaneous Radiofrequency Ablation Using Internally Cooled Wet Electrodes for the Treatment of Hepatocellular Carcinoma. American Journal of Roentgenology, 198(2), 471-476. doi:10.2214/ajr.11.6583Kim, J. W., Kim, J. H., Shin, Y. M., Won, H. J., & Kim, P. N. (2014). Percutaneous radiofrequency ablation with internally cooled wet electrodes versus cluster electrodes for the treatment of single medium-sized hepatocellular carcinoma. Gastrointestinal Intervention, 3(2), 98-103. doi:10.1016/j.gii.2014.09.008Jo, B., & Aksan, A. (2010). Prediction of the extent of thermal damage in the cornea during conductive keratoplasty. Journal of Thermal Biology, 35(4), 167-174. doi:10.1016/j.jtherbio.2010.02.004Haemmerich, D., Chachati, L., Wright, A. S., Mahvi, D. M., Lee, F. T., & Webster, J. G. (2003). Hepatic radiofrequency ablation with internally cooled probes: effect of coolant temperature on lesion size. IEEE Transactions on Biomedical Engineering, 50(4), 493-500. doi:10.1109/tbme.2003.809488Demazumder, D., Mirotznik, M. S., & Schwartzman, D. (2001). Journal of Interventional Cardiac Electrophysiology, 5(4), 377-389. doi:10.1023/a:1013224110550Antunes, C. L., Almeida, T. R. O., & Raposeiro, N. (2012). Saline‐enhanced RF ablation on a cholangiocarcinoma: a numerical simulation. COMPEL - The international journal for computation and mathematics in electrical and electronic engineering, 31(4), 1055-1066. doi:10.1108/03321641211227302Pätz T, Kröger T, Preusser T. (2009). Simulation of radiofrequency ablation including water evaporation. IFMBE Proceedings, 25/IV:1287–90.Berjano, E. J., Burdío, F., Navarro, A. C., Burdío, J. M., Güemes, A., Aldana, O., … Gregorio, M. A. de. (2006). Improved perfusion system for bipolar radiofrequency ablation of liver: preliminary findings from a computer modeling study. Physiological Measurement, 27(10), N55-N66. doi:10.1088/0967-3334/27/10/n03McGahan, J. P., Loh, S., Boschini, F. J., Paoli, E. E., Brock, J. M., Monsky, W. L., & Li, C.-S. (2010). Maximizing Parameters for Tissue Ablation by Using an Internally Cooled Electrode. Radiology, 256(2), 397-405. doi:10.1148/radiol.09090662Doss, J. D. (1982). Calculation of electric fields in conductive media. Medical Physics, 9(4), 566-573. doi:10.1118/1.595107Tungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., & Webster, J. G. (2000). Thermal—electrical finite element modelling for radio frequency cardiac ablation: Effects of changes in myocardial properties. Medical & Biological Engineering & Computing, 38(5), 562-568. doi:10.1007/bf02345754Hall, S. K., Ooi, E. H., & Payne, S. J. (2015). Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation. International Journal of Hyperthermia, 31(5), 538-550. doi:10.3109/02656736.2015.1032370Beop-Min Kim, Jacques, S. L., Rastegar, S., Thomsen, S., & Motamedi, M. (1996). Nonlinear finite-element analysis of the role of dynamic changes in blood perfusion and optical properties in laser coagulation of tissue. IEEE Journal of Selected Topics in Quantum Electronics, 2(4), 922-933. doi:10.1109/2944.577317Goldberg, S. N., Stein, M. C., Gazelle, G. S., Sheiman, R. G., Kruskal, J. B., & Clouse, M. E. (1999). Percutaneous Radiofrequency Tissue Ablation: Optimization of Pulsed-Radiofrequency Technique to Increase Coagulation Necrosis. Journal of Vascular and Interventional Radiology, 10(7), 907-916. doi:10.1016/s1051-0443(99)70136-3Trujillo, M., & Berjano, E. (2013). Review of the mathematical functions used to model the temperature dependence of electrical and thermal conductivities of biological tissue in radiofrequency ablation. International Journal of Hyperthermia, 29(6), 590-597. doi:10.3109/02656736.2013.807438Abraham, J. P., & Sparrow, E. M. (2007). A thermal-ablation bioheat model including liquid-to-vapor phase change, pressure- and necrosis-dependent perfusion, and moisture-dependent properties. International Journal of Heat and Mass Transfer, 50(13-14), 2537-2544. doi:10.1016/j.ijheatmasstransfer.2006.11.045Yang, D., Converse, M. C., Mahvi, D. M., & Webster, J. G. (2007). Expanding the Bioheat Equation to Include Tissue Internal Water Evaporation During Heating. IEEE Transactions on Biomedical Engineering, 54(8), 1382-1388. doi:10.1109/tbme.2007.890740Baxter, L. T., & Jain, R. K. (1989). Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection. Microvascular Research, 37(1), 77-104. doi:10.1016/0026-2862(89)90074-5Burdío, F., Berjano, E., Millan, O., Grande, L., Poves, I., Silva, C., … Mojal, S. (2013). CT mapping of saline distribution after infusion of saline into the liver in an ex vivo animal model. How much tissue is actually infused in an image-guided procedure? Physica Medica, 29(2), 188-195. doi:10.1016/j.ejmp.2012.03.001Uthamanthil, R. K., Edwards, R. B., Lu, Y., Manley, P. A., Athanasiou, K. A., & Markel, M. D. (2006). In vivo study on the short-term effect of radiofrequency energy on chondromalacic patellar cartilage and its correlation with calcified cartilage pathology in an equine model. Journal of Orthopaedic Research, 24(4), 716-724. doi:10.1002/jor.20108Nour SG, Lewin JS, Duerk JL. (2001). Saline injection in ex-vivo liver: monitoring with fast gradient echo sequences At 0.2 T, Glasgow, Scotland. Proceedings of the International Society for Magnetic Resonance in Medicine (ISMRM) 9th Scientific Meeting.Schutt, D. J., & Haemmerich, D. (2008). Effects of variation in perfusion rates and of perfusion models in computational models of radio frequency tumor ablation. Medical Physics, 35(8), 3462-3470. doi:10.1118/1.2948388Myong-Ki Jun KD. (2006). Electrode for radiofrequency tissue ablation. US Patent US 2006/0122593, June 8, 2006.Lee, J. M., Han, J. K., Kim, S. H., Han, C. J., An, S. K., Lee, J. Y., & Choi, B. I. (2005). Wet radio-frequency ablation using multiple electrodes: comparative study of bipolar versus monopolar modes in the bovine liver. European Journal of Radiology, 54(3), 408-417. doi:10.1016/j.ejrad.2004.06.004Lee, J. M., Han, J. K., Kim, S. H., Lee, J. Y., Kim, D. J., Lee, M. W., … Choi, B. I. (2004). Saline-Enhanced Hepatic Radiofrequency Ablation Using a Perfused-Cooled Electrode: Comparison of Dual Probe Bipolar Mode with Monopolar and Single Probe Bipolar Modes. Korean Journal of Radiology, 5(2), 121. doi:10.3348/kjr.2004.5.2.121Ishikawa, T. (2013). Radiofrequency ablation during continuous saline infusion can extend ablation margins. World Journal of Gastroenterology, 19(8), 1278. doi:10.3748/wjg.v19.i8.127

Low-temperature muon spin rotation studies of the monopole charges and currents in Y doped Ho2Ti2O7

In the ground state of Ho2Ti2O7 spin ice, the disorder of the magnetic moments follows the same rules as the proton disorder in water ice. Excitations take the form of magnetic monopoles that interact via a magnetic Coulomb interaction. Muon spin rotation has been used to probe the low-temperature magnetic behaviour in single crystal Ho2−xYxTi2O7 (x = 0, 0.1, 1, 1.6 and 2). At very low temperatures, a linear field dependence for the relaxation rate of the muon precession λ(B), that in some previous experiments on Dy2Ti2O7 spin ice has been associated with monopole currents, is observed in samples with x = 0, and 0.1. A signal from the magnetic fields penetrating into the silver sample plate due to the magnetization of the crystals is observed for all the samples containing Ho allowing us to study the unusual magnetic dynamics of Y doped spin ice

Automatic control of finite element models for temperature-controlled radiofrequency ablation

BACKGROUND: The finite element method (FEM) has been used to simulate cardiac and hepatic radiofrequency (RF) ablation. The FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. In both hepatic and cardiac RF ablation a common control mode is temperature-controlled mode. Commercial FEM packages don't support automating temperature control. Most researchers manually control the applied power by trial and error to keep the tip temperature of the electrodes constant. METHODS: We implemented a PI controller in a control program written in C++. The program checks the tip temperature after each step and controls the applied voltage to keep temperature constant. We created a closed loop system consisting of a FEM model and the software controlling the applied voltage. The control parameters for the controller were optimized using a closed loop system simulation. RESULTS: We present results of a temperature controlled 3-D FEM model of a RITA model 30 electrode. The control software effectively controlled applied voltage in the FEM model to obtain, and keep electrodes at target temperature of 100°C. The closed loop system simulation output closely correlated with the FEM model, and allowed us to optimize control parameters. DISCUSSION: The closed loop control of the FEM model allowed us to implement temperature controlled RF ablation with minimal user input

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs

Although thoracic vertebral malformations with kyphosis and scoliosis are often considered incidental findings on diagnostic imaging studies of screw-tailed brachycephalic breeds, they have been suggested to interfere with spinal biomechanics and intervertebral disc degeneration. It is however unknown if an abnormal spinal curvature also predisposes dogs to develop clinically relevant intervertebral disc herniations. The aim of this study was to evaluate if the occurrence of thoracic vertebral malformations, kyphosis or scoliosis would be associated with a higher prevalence of cervical or thoracolumbar intervertebral disc extrusion in French bulldogs

Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported

The Internal Sequence of the Peptide-Substrate Determines Its N-Terminus Trimming by ERAP1

Background: Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims N-terminally extended antigenic peptide precursors down to mature antigenic peptides for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 has unique properties for an aminopeptidase being able to trim peptides in vitro based on their length and the nature of their C-termini. Methodology/Principal Findings: In an effort to better understand the molecular mechanism that ERAP1 uses to trim peptides, we systematically analyzed the enzyme's substrate preferences using collections of peptide substrates. We discovered strong internal sequence preferences of peptide N-terminus trimming by ERAP1. Preferences were only found for positively charged or hydrophobic residues resulting to trimming rate changes by up to 100 fold for single residue substitutions and more than 40,000 fold for multiple residue substitutions for peptides with identical N-termini. Molecular modelling of ERAP1 revealed a large internal cavity that carries a strong negative electrostatic potential and is large enough to accommodate peptides adjacent to the enzyme's active site. This model can readily account for the strong preference for positively charged side chains. Conclusions/Significance: To our knowledge no other aminopeptidase has been described to have such strong preferences for internal residues so distal to the N-terminus. Overall, our findings indicate that the internal sequence of the peptide can affect its trimming by ERAP1 as much as the peptide's length and C-terminus. We therefore propose that ERAP1 recognizes the full length of its peptide-substrate and not just the N- and C- termini. It is possible that ERAP1 trimming preferences influence the rate of generation and the composition of antigenic peptides in vivo

Finite Element Analysis of Hepatic Radiofrequency Ablation Probes using Temperature-Dependent Electrical Conductivity

BACKGROUND: Few finite element models (FEM) have been developed to describe the electric field, specific absorption rate (SAR), and the temperature distribution surrounding hepatic radiofrequency ablation probes. To date, a coupled finite element model that accounts for the temperature-dependent electrical conductivity changes has not been developed for ablation type devices. While it is widely acknowledged that accounting for temperature dependent phenomena may affect the outcome of these models, the effect has not been assessed. METHODS: The results of four finite element models are compared: constant electrical conductivity without tissue perfusion, temperature-dependent conductivity without tissue perfusion, constant electrical conductivity with tissue perfusion, and temperature-dependent conductivity with tissue perfusion. RESULTS: The data demonstrate that significant errors are generated when constant electrical conductivity is assumed in coupled electrical-heat transfer problems that operate at high temperatures. These errors appear to be closely related to the temperature at which the ablation device operates and not to the amount of power applied by the device or the state of tissue perfusion. CONCLUSION: Accounting for temperature-dependent phenomena may be critically important in the safe operation of radiofrequency ablation device that operate near 100°C