Hearts Ablaze: Radio Frequency Ablation as Treatment for Cardiac Arrythmia

This project analyzes several of the parameters involved in the use of radiofrequency ablation (RFA) in the treatment of cardiac arrhythmia. Arrhythmia is an irregular beating of the heart that can be caused by improperly timed contractions within the heart, which can, in certain circumstances, be corrected by ablating tissue. One out of every five hundred people is born with an arrhythmia and others acquire the condition through heart disease. For heart attack victims, it is the most common cause of sudden death. RFA is a common way to treat serious arrhythmia cases by cutting the short circuit through the destruction of certain tissues. We used finite element analysis along with prototyping software to determine the duration of treatment, with special attention to the damage caused to surrounding tissue. We found that the optimal parameters for most effective treatment were to administer 30V for 120 seconds ? which happens to be the standard method of operation. This destroys the necessary part of the AV node while maintaining the surrounding tissue at relatively normal temperatures

Cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: Experimental study based on an agar phantom

[EN] A great deal of current research is directed to finding a way to minimize thermal injury in the esophagus during radiofrequency catheter ablation of the atrium. A recent clinical study employing a cooling intraesophageal balloon reported a reduction of the temperature in the esophageal lumen. However, it could not be determined whether the deeper muscular layer of the esophagus was cooled enough to prevent injury. We built a model based on an agar phantom in order to experimentally study the thermal behavior of this balloon by measuring the temperature not only on the balloon, but also at a hypothetical point between the esophageal lumen and myocardium (2 mm distant). Controlled temperature (55 degrees C) ablations were conducted for 120 s. The results showed that (1) the cooling balloon provides a reduction in the final temperature reached, both on the balloon surface and at a distance of 2 mm; (2) coolant temperature has a significant effect on the temperature measured at 2 mm from the esophageal lumen (it has a less effect on the temperature measured on the balloon surface) and (3) the pre- cooling period has a significant effect on the temperature measured on the balloon surface (the effect on the temperaturemeasured 2mmaway is small). The results were in good agreement with those obtained in a previous clinical study. The study suggests that the cooling balloon gives thermal protection to the esophagus when a minimum pre- cooling period of 2 min is programmed at a coolant temperature of 5 degrees C or less.We would like to thank the R+D+i Linguistic Assistance Office at the Technical Universityof Valencia for their help in revising this paper. This work was partially financially supported by the ‘Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Educación y Ciencia of Spain (TEC 2005-04199/TCM) and by an R&D contract (CSIC-20060633) between Edwards Life science Ltd. and the Spanish Council for ScientificResearch (CSIC).Lequerica, JL.; Berjano, E.; Herrero, M.; Melecio, L.; Hornero, F. (2008). Cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: Experimental study based on an agar phantom. Physics in Medicine and Biology. 53:25-34. https://doi.org/10.1088/0031-9155/53/4/N01S25345

Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model

[EN] Although previous studies have established the feasibility of monitoring esophageal temperature during radiofrequency cardiac ablation using an esophageal temperature probe (ETP), some questions remain regarding its efficacy. The aims of this study were to study the effect of the location of the ETP on the temperature reached, and to test the characteristics of ETP as used in clinical practice. We constructed an agar phantom to model the thermal and electrical characteristics of the biological tissues (left atrium, esophagus and connective tissue). The ETP was positioned at 6.5 mm from an ablation electrode and at distances of 0, 5, 10, 15, 20 mm from the catheter axis. A thermocouple was located on the probe to measure the actual temperature of the external esophageal layer during the ablations (55 degrees C, 60 s). The mean temperatures reached at the thermocouple were significantly higher than those measured by the ETP (48.3 +/- 1.9 degrees C versus 39.6 +/- 1.1 degrees C). The temperature values measured with the ETP were significantly lower when the probe was located further from the catheter axis ( up to 2.5 degrees C lower when the distance from the probe - catheter axis was 2 cm). The dynamic calibration of the ETP showed a mean value for the time constant of 8 s. In conclusion, the temperature measured by the ETP always underestimates the temperature reached in the thermocouple. This fact can be explained by the distance gap between the thermocouple and probe and by the dynamic response of the ETP. The longer the distance between the ETP and catheter axis, the higher is the temperature difference.We would like to thank the R+D+i Linguistic Assistance Office at the Universidad Politécnica of Valencia for its help in revising this paper. This work was partially supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Educación y Ciencia of Spain (TEC 2005-04199/TCM) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd. and the Spanish Council for Scientific Research (CSIC).Rodriguez, I.; Lequerica, JL.; Berjano, E.; Herrero, M.; Hornero, F. (2007). Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model. Physiological Measurement. 28(5):453-463. https://doi.org/10.1088/0967-3334/28/5/001S453463285Berjano, E. J., & Hornero, F. (2005). What affects esophageal injury during radiofrequency ablation of the left atrium? An engineering study based on finite-element analysis. Physiological Measurement, 26(5), 837-848. doi:10.1088/0967-3334/26/5/020Hong Cao, Vorperian, V. R., Jang-Zem Tsai, Tungjitkusolmun, S., Eung Je Woo, & Webster, J. G. (2000). Temperature measurement within myocardium during in vitro RF catheter ablation. IEEE Transactions on Biomedical Engineering, 47(11), 1518-1524. doi:10.1109/10.880104Cappato, R., Calkins, H., Chen, S.-A., Davies, W., Iesaka, Y., Kalman, J., … Skanes, A. (2005). Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation. Circulation, 111(9), 1100-1105. doi:10.1161/01.cir.0000157153.30978.67Cummings, J. E., Schweikert, R. A., Saliba, W. I., Burkhardt, J. D., Brachmann, J., Gunther, J., … Natale, A. (2005). Assessment of Temperature, Proximity, and Course of the Esophagus During Radiofrequency Ablation Within the Left Atrium. Circulation, 112(4), 459-464. doi:10.1161/circulationaha.104.509612D‘avila, A., Maldonado, P., Veronese, F., Mendonça, M. L. F., Colafranceschi, A. S., Colle, S., & Saad, E. B. (2005). Accuracy of esophageal temperature measurement and its correlation to microbubbles formation during catheter ablation of atrial fibrillation. Heart Rhythm, 2(5), S9. doi:10.1016/j.hrthm.2005.02.040Doll, N., Borger, M. A., Fabricius, A., Stephan, S., Gummert, J., Mohr, F. W., … Hindricks, G. (2003). Esophageal perforation during left atrial radiofrequency ablation: Is the risk too high? The Journal of Thoracic and Cardiovascular Surgery, 125(4), 836-842. doi:10.1067/mtc.2003.165Gillinov, A. M., Pettersson, G., & Rice, T. W. (2001). Esophageal injury during radiofrequency ablation for atrial fibrillation. The Journal of Thoracic and Cardiovascular Surgery, 122(6), 1239-1240. doi:10.1067/mtc.2001.118041Goldberg, 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.r01ap27157YEN HO, S., SANCHEZ-QUINTANA, D., CABRERA, J. A., & ANDERSON, R. H. (1999). Anatomy of the Left Atrium:. Journal of Cardiovascular Electrophysiology, 10(11), 1525-1533. doi:10.1111/j.1540-8167.1999.tb00211.xHORNERO, F., & BERJANO, E. J. (2006). Esophageal Temperature During Radiofrequency-Catheter Ablation of Left Atrium: A Three-Dimensional Computer Modeling Study. Journal of Cardiovascular Electrophysiology, 17(4), 405-410. doi:10.1111/j.1540-8167.2006.00404.xJain, M. K., & Wolf, P. D. (2000). In Vitro Temperature Map of Cardiac Ablation Demonstrates the Effect of Flow on Lesion Development. Annals of Biomedical Engineering, 28(9), 1066-1074. doi:10.1114/1.1310218Kuwahara, T., Takahashi, A., Yokoyama, Y., Kobori, A., Sato, A., Iesaka, Y., … Aonuma, K. (2005). Importance of esophageal temperature monitoring for the avoidance of esophageal injury during circumferential left atrial ablation. Heart Rhythm, 2(5), S156. doi:10.1016/j.hrthm.2005.02.487Lemola, K., Sneider, M., Desjardins, B., Case, I., Han, J., Good, E., … Oral, H. (2004). Computed Tomographic Analysis of the Anatomy of the Left Atrium and the Esophagus. Circulation, 110(24), 3655-3660. doi:10.1161/01.cir.0000149714.31471.fdLobo, 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.2301021512Meade, T., Razavi, M., Yang, D., Delapasse, S., Donsky, A., Ai, T., … Cheng, J. (2005). Real-time esophageal thermal profile during posterior left atrial radiofrequency ablation. Heart Rhythm, 2(5), S236. doi:10.1016/j.hrthm.2005.02.738Pappone, C., Oral, H., Santinelli, V., Vicedomini, G., Lang, C. C., Manguso, F., … Morady, F. (2004). Atrio-Esophageal Fistula as a Complication of Percutaneous Transcatheter Ablation of Atrial Fibrillation. Circulation, 109(22), 2724-2726. doi:10.1161/01.cir.0000131866.44650.46PERZANOWSKI, C., TEPLITSKY, L., HRANITZKY, P. M., & BAHNSON, T. D. (2006). Real-Time Monitoring of Luminal Esophageal Temperature During Left Atrial Radiofrequency Catheter Ablation for Atrial Fibrillation: Observations About Esophageal Heating During Ablation at the Pulmonary Vein Ostia and Posterior Left Atrium. Journal of Cardiovascular Electrophysiology, 17(2), 166-170. doi:10.1111/j.1540-8167.2005.00333.xPiorkowski, C., Hindricks, G., Schreiber, D., Tanner, H., Weise, W., Koch, A., … Kottkamp, H. (2006). Electroanatomic reconstruction of the left atrium, pulmonary veins, and esophagus compared with the «true anatomy» on multislice computed tomography in patients undergoing catheter ablation of atrial fibrillation. Heart Rhythm, 3(3), 317-327. doi:10.1016/j.hrthm.2005.11.027REDFEARN, D. P., TRIM, G. M., SKANES, A. C., PETRELLIS, B., KRAHN, A. D., YEE, R., & KLEIN, G. J. (2005). Esophageal Temperature Monitoring During Radiofrequency Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 16(6), 589-593. doi:10.1111/j.1540-8167.2005.40825.xSánchez-Quintana, D., Cabrera, J. A., Climent, V., Farré, J., de Mendonça, M. C., & Ho, S. Y. (2005). Anatomic Relations Between the Esophagus and Left Atrium and Relevance for Ablation of Atrial Fibrillation. Circulation, 112(10), 1400-1405. doi:10.1161/circulationaha.105.551291SCANAVACCA, M. I., D’ÁVILA, A., PARGA, J., & SOSA, E. (2004). Left Atrial-Esophageal Fistula Following Radiofrequency Catheter Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 15(8), 960-962. doi:10.1046/j.1540-8167.2004.04083.xSolazzo, S. A., Liu, Z., Lobo, S. M., Ahmed, M., Hines-Peralta, A. U., Lenkinski, R. E., & Goldberg, S. N. (2005). Radiofrequency Ablation: Importance of Background Tissue Electrical Conductivity—An Agar Phantom and Computer Modeling Study. Radiology, 236(2), 495-502. doi:10.1148/radiol.2362040965Teplitsky, L., Perzanowski, C., Durrani, S., Berman, A. E., Hranitzky, P., & Bahnson, T. D. (2005). Radiofrequency catheter ablation for atrial fibrillation produces delayed and long lasting elevation of luminal esophageal temperature independent of lesion duration and power. Heart Rhythm, 2(5), S8-S9. doi:10.1016/j.hrthm.2005.02.038Tsao, H.-M., Wu, M.-H., Higa, S., Lee, K.-T., Tai, C.-T., Hsu, N.-W., … Chen, S.-A. (2005). Anatomic Relationship of the Esophagus and Left Atrium. Chest, 128(4), 2581-2587. doi:10.1378/chest.128.4.2581Wittkampf, F. H. M., Nakagawa, H., Yamanashi, W. S., Imai, S., & Jackman, W. M. (1996). Thermal Latency in Radiofrequency Ablation. Circulation, 93(6), 1083-1086. doi:10.1161/01.cir.93.6.108

Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/0967-3334/31/4/009[EN] The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min¿1). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 °C; (3) substantial errors (larger than 15 °C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 °C).This work was supported by the 'Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica del Ministerio de Educacion y Ciencia' of Spain (TEC200801369/ TEC) and by an R&D contract (CSIC-20060633) between Edwards Lifescience Ltd and the Spanish National Research Council (CSIC). The English revision and correction of this paper was funded by the Universidad Politecnica de Valencia, Spain. We thank L Melecio for his invaluable technical support in conducting the experiments.Blasco-Giménez, R.; Lequerica, JL.; Herrero, M.; Hornero, F.; Berjano, E. (2010). Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model. Physiological Measurement. 31(4):581-594. https://doi.org/10.1088/0967-3334/31/4/009S581594314Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459Hong Cao, Vorperian, V. R., Jang-Zem Tsai, Tungjitkusolmun, S., Eung Je Woo, & Webster, J. G. (2000). Temperature measurement within myocardium during in vitro RF catheter ablation. IEEE Transactions on Biomedical Engineering, 47(11), 1518-1524. doi:10.1109/10.880104Hamner, C. E., Potter, D. D., Cho, K. R., Lutterman, A., Francischelli, D., Sundt, T. M., & Schaff, H. V. (2005). Irrigated Radiofrequency Ablation With Transmurality Feedback Reliably Produces Cox Maze Lesions In Vivo. The Annals of Thoracic Surgery, 80(6), 2263-2270. doi:10.1016/j.athoracsur.2005.06.017HARTUNG, W. M., BURTON, M. E., DEAM, A. G., WALTER, P. F., McTEAGUE, K., & LANGBERG, J. J. (1995). Estimation of Temperature During Radiofrequency Catheter Ablation Using Impedance Measurements. Pacing and Clinical Electrophysiology, 18(11), 2017-2021. doi:10.1111/j.1540-8159.1995.tb03862.xDing Sheng He, Bosnos, M., Mays, M. Z., & Marcus, F. (2003). Assessment of myocardial lesion size during in vitro radio frequency catheter ablation. IEEE Transactions on Biomedical Engineering, 50(6), 768-776. doi:10.1109/tbme.2003.812161KO, W.-C., HUANG, S. K. S., LIN, J.-L., SHAU, W.-Y., LAI, L.-P., & CHEN, P. H. (2001). New Method for Predicting Efficiency of Heating by Measuring Bioimpedance During Radiofrequency Catheter Ablation in Humans. Journal of Cardiovascular Electrophysiology, 12(7), 819-823. doi:10.1046/j.1540-8167.2001.00819.xLabonte, S. (1994). Numerical model for radio-frequency ablation of the endocardium and its experimental validation. IEEE Transactions on Biomedical Engineering, 41(2), 108-115. doi:10.1109/10.284921Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Lequerica, J. L., Berjano, E. J., Herrero, M., Melecio, L., & Hornero, F. (2008). A cooled water-irrigated intraesophageal balloon to prevent thermal injury during cardiac ablation: experimental study based on an agar phantom. Physics in Medicine and Biology, 53(4), N25-N34. doi:10.1088/0031-9155/53/4/n01Mattingly, M., Bailey, E. A., Dutton, A. W., Roemer, R. B., & Devasia, S. (1998). Reduced-order modeling for hyperthermia: an extended balanced-realization-based approach. IEEE Transactions on Biomedical Engineering, 45(9), 1154-1162. doi:10.1109/10.709559PILCHER, T. A., SANFORD, A. L., SAUL, J. P., & HAEMMERICH, D. (2006). Convective Cooling Effect on Cooled-Tip Catheter Compared to Large-Tip Catheter Radiofrequency Ablation. Pacing and Clinical Electrophysiology, 29(12), 1368-1374. doi:10.1111/j.1540-8159.2006.00549.xRodríguez, I., Lequerica, J. L., Berjano, E. J., Herrero, M., & Hornero, F. (2007). Esophageal temperature monitoring during radiofrequency catheter ablation: experimental study based on an agar phantom model. Physiological Measurement, 28(5), 453-463. doi:10.1088/0967-3334/28/5/001SCHUMACHER, B., EICK, O., WITTKAMPF, F., PEZOLD, C., TEBBENJOHANNS, J., JUNG, W., & LUDERITZ, B. (1999). Temperature Response Following Nontraumatic Low Power Radiofrequency Application. Pacing and Clinical Electrophysiology, 22(2), 339-343. doi:10.1111/j.1540-8159.1999.tb00448.xTeixeira, C. A., Ruano, A. E., Ruano, M. G., Pereira, W. C. A., & Negreira, C. (2006). Non-invasive temperature prediction of in vitro therapeutic ultrasound signals using neural networks. Medical & Biological Engineering & Computing, 44(1-2), 111-116. doi:10.1007/s11517-005-0004-2Teixeira, C. A., Ruano, M. G., Ruano, A. E., & Pereira, W. C. A. (2008). A Soft-Computing Methodology for Noninvasive Time-Spatial Temperature Estimation. IEEE Transactions on Biomedical Engineering, 55(2), 572-580. doi:10.1109/tbme.2007.90102

A Theoretical and Experimental Analysis of Radiofrequency Ablation with a Multielectrode, Phased, Duty-Cycled System

Background:   The development of a unique radiofrequency (RF) cardiac ablation system, for the treatment of cardiac arrhythmias, is driven by the clinical need to safely create large uniform lesions while controlling lesion depth. Computational analysis of a finite element model of a three-dimensional, multielectrode, cardiac ablation catheter, powered by a temperature-controlled, multiphase, duty-cycled RF generator, is presented. Methods:   The computational model for each of the five operating modes offered by the generator is compared to independent tissue temperature measurements taken during in vitro ablation experiments performed on bovine myocardium. Results:   The results of the model agree with experimental temperature measurements very closely—the average values for mean error, root mean square difference, and correlation coefficient were 1.9°C, 13.3%, and 0.97, respectively. Lesions are shown to be contiguous and no significant edge effects are observed. Conclusions:   Both the in vitro and computational model results demonstrate that lesion depth decreases consistently as the bipolar-to-unipolar ratio increases—suggesting a clinical application to potentially control lesion depth with higher fidelity than is currently available. The effect of variable design parameters and clinical conditions on RF ablation can now be expeditiously studied with this validated model. (PACE 2010; 33:1089–1100)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79205/1/j.1540-8159.2010.02801.x.pd

Darstellung intramyokardialer Temperaturphänomene während der Radiofrequenz-Katheterablation mittels Thermografie im In-vitro-Modell

Ziel der Untersuchung war die Entwicklung eines In-vitro-Modells zur Evaluierung von Ablationskathetern für die Therapie von Herzrhythmusstörungen, die durch thermische Prozesse eine Modifikation des Myokards bewirken. Hierzu wurde erstmals die Technik der modernen Thermografie angewandt. Diese ermöglicht während der Ablation eine Online-Registrierung von Temperaturprozessen an jedem beliebigen Ort im Myokardquerschnitt mit einer Auflösung von 0,1mm und einer Messgenauigkeit von 0,1°C. Ebenfalls lassen sich die Temperaturprozesse zweidimensional in Falschfarbenbildern darstellen. Durch die kontaktfreie Technik der Thermografie konnte auf intramyokardiale Temperatursonden verzichtet werden, welche in ihrer Positionierung meist schwierig standardisierbar sind und selbst zu störenden Effekten und somit Messfehlern während der Stromabgabe führen können. Als optisches Medium zwischen Myokard und Thermografiekamera wurde Saphirglas mit einer Transmission von 92% verwendet. Das Modell konnte mit Hilfe eines Schwarzen Strahlers in seiner Messgenauigkeit und Aussagekraft validiert werden. Im zweiten Teil der Studie wurden drei verschiedene Ablationskatheter (4mm-, 8mm- und eine gekühlte 4mm-Elektrodenspitze) mit dem vorgestellten Versuchsmodell auf ihre thermischen Eigenschaften während der Ablation in n=105 Messreihen bei unterschiedlichen Ablationsleistungen untersucht. Neben den bereits in der Literatur beschriebenen Temperaturphänomenen war es mit dem vorgestellten Versuchsmodell erstmals möglich Prozesse nachzuweisen, welche bisher nur in mathematisch-numerischen Modellen postuliert werden konnten (Bsp. Temperaturverteilung im Perfusionsstrom an der Myokardoberfläche). Ebenfalls zeigte sich eine hohe Korrelation zwischen den Temperaturverteilungsmustern und den resultierenden Nekrosezonen im Myokard, was die rein thermische Alteration des Myokards während der Ablation erneut beweisen konnte. Prinzipiell kann mit dem vorgestellten In-vitro-Modell jedes Ablationssystem auf seine Eigenschaften untersucht werden, welches eine thermische Veränderung des Ablationssubstrats bewirkt. Durch eine geringe Kostenintensität und eine gute Reproduzierbarkeit könnte dieses Modell außerdem zu einer Einsparung von Tierversuchen führen

Acoustic Radiation Force Impulse Imaging of Radiofrequency Ablation Lesions for Cardiac Ablation Procedures

<p>This dissertation investigates the use of intraprocedure acoustic radiation force impulse (ARFI) imaging for visualization of radiofrequency ablation (RFA) lesions during cardiac transcatheter ablation (TCA) procedures. Tens of thousands of TCA procedures are performed annually to treat atrial fibrillation (AF) and other cardiac arrhythmias. Despite the use of sophisticated electroanatomical mapping (EAM) techniques to validate the modification of the electrical substrate, post-procedure arrhythmia recurrence is common due to incomplete lesion delivery and electrical conduction through lesion line discontinuities. The clinical demand for an imaging modality that can visually confirm the presence and completeness of RFA lesion lines motivated this research.</p><p>ARFI imaging is an ultrasound-based technique that transmits radiation force impulses to locally displace tissue and uses the tissue deformation response to generate images of relative tissue stiffness. RF-induced heating causes irreversible tissue necrosis and contractile protein denaturation that increases the stiffness of the ablated region. Preliminary in vitro and in vivo feasibility studies determined RF ablated myocardium appears stiffer in ARFI images.</p><p>This thesis describes results for ARFI imaging of RFA lesions for three research milestones: 1) an in vivo experimental verification model, 2) a clinically translative animal study, and 3) a preliminary clinical feasibility trial in human patients. In all studies, 2-D ARFI images were acquired in normal sinus rhythm and during diastole to maximize the stiffness contrast between the ablated and unablated myocardium and to minimize the bulk cardiac motion during the acquisition time.</p><p>The first in vivo experiment confirmed there was a significant decrease in the measured ARFI-induced displacement at ablation sites during and after focal RFA; the displacements in the lesion border zone and the detected lesion area stabilized over the first several minutes post-ablation. The implications of these results for ARFI imaging methods and the clinical relevance of the findings are discussed.</p><p>The second and third research chapters of this thesis describe the system integration and implementation of a multi-modality intracardiac ARFI imaging-EAM system for intraprocedure lesion evaluation. EAM was used to guide the 2-D ARFI imaging plane to targeted ablation sites in the canine right atrium (RA); the presence of EAM lesions markers and conduction disturbances in the local activation time (LAT) maps were used to find the sensitivity and specificity of predicting the presence of RFA lesion with ARFI imaging. The contrast and contrast-to-noise ratio between RFA lesion and unablated myocardium were calculated for ARFI and conventional ICE images. The opportunities and potential developments for clinical translation are discussed. </p><p>The last research chapter in this thesis describes a feasibility study of intracardiac ARFI imaging of RFA lesions in clinical patients. ARFI images of clinically relevant ablation sites were acquired, and this pilot study determined ARFI-induced displacements in human myocardium decreased at targeted ablation sites after RF-delivery. The challenges and successes of this pilot study are discussed.</p><p>This work provides evidence that intraprocedure ARFI imaging is a promising technology for the visualization of RFA lesions during cardiac TCA procedures. The clinical significance of this research is discussed, as well as challenges and considerations for future iterations of this technology aiming for clinical translation.</p>Dissertatio

Eficacia y seguridad de la desconexión eléctrica de las venas pulmonares mediante aplicaciones de radiofrecuencia de alta potencia y corta duración en pacientes con fibrilación auricular

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 10-07-202

Simple and low-cost manufacturing of customisable drug delivery devices and flexible sensors for biomedical applications

In recent years, 3D printing technologies have been adopted into the medical and pharmaceutical industry for the fabrication of personalised medicines, oral dosage forms, medical implants, medical devices, tissue engineering applications, and many more. However, the use of 3D printing, in particular the low-cost Fused Deposition Modelling (FDM) 3D printing technique, has been limited due to the limited number of biocompatible materials suitable for pharmaceutical and biomedical applications. In this study, the FDM 3D printing technique was being explored for the fabrication of pharmaceutical products as it is the most widely available and easily accessible 3D printing technology. In order to improve the usability of FDM 3D printing for pharmaceutical and biomedical applications, the studies to fabricate several different biocompatible filaments composition that can be used for drug loading were carried out. Firstly, filaments made of several pharmaceutical grade polymers were being developed using hot-melt extrusion (HME). Three types of biocompatible polymeric filaments have been developed. They are (Polylactic Acid) PLA-based, (Hydroxypropyl Cellulose) HPC-based and (Polycaprolactone) PCL-based. These filaments were added with a plasticiser, polyethylene glycol (PEG), to improve their processability and physicochemical properties of the produced filaments so that they can used in an FDM 3D printer. The HPC-based filaments were loaded with a model drug, theophylline, that exhibits poor aqueous solubility, whereas the PCL-based filaments were loaded with a readily soluble model drug, metformin. The studies showed that the filaments were effective in sustaining the release of both drug, and the sustain release properties of the filaments can be adjusted by altering the composition of the polymers. The studies showed that the HME technology is very compatible with FDM 3D printing as it is able to produce 3D printable filaments by mixing different polymeric materials. The filaments can also be loaded with a desired drug at a required dose to allow the 3D printing of drug delivery systems. This technique allows the fabrication of personalised drug delivery systems in-house. It can be beneficial for clinics and hospitals in remote areas as the lead times can be reduced when in-house fabrication is possible. The ability to fabricate personalised medicines at hand also means that the dose can drug release patterns can be altered for the patients at any point of time when required. Apart from that, this technique can change way medicines are transported and stored, which could potentially help save cost on transportation and inventory. In addition to medicines, the FDM 3D printing technique can also be used to produce other personalised drug delivery systems such as microneedles, braces and implants of various shapes due to the flexibility of the 3D printing process. The other aspect of this research was on the fabrication of biomedical sensors that can potentially be integrated with the 3D printed drug delivery systems to form a smart drug delivery device. The idea of smart drug delivery device is that it is capable of continuous monitoring the health of a patient and then administer drug to the patient whenever it is required. The development of such smart medical devices has been one of the hottest interests in the biomedical sector. One of the main issues with such technologies is the high cost which has caused the technologies to be not so affordable for many people. Therefore, the studies to fabricate some simple biomedical sensors such as a temperature sensor and a glucose sensor using simple and cost-effective manufacturing technique were being explored. The fabrication techniques used are FDM 3D printing and a thin-film fabrication technique that involves deposition of material using a thermal evaporator. Low-cost manufacturing techniques were being explored in order to help reduce manufacturing cost which could help improve the affordability of such technologies. The fabricated temperature and glucose sensors exhibit great stability in performance and mechanical flexibility. The flexibility allows the sensors to be conformable to curved surfaces such as the skin. Hence, the sensors are suitable to be used as a wearable device or integrated into some other medical devices to form a smart medical device