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Cryosurgical ablation in the gastrointestinal tract: Development of a novel cryosurgical platform
Abstracts / Cryobiology 73 (2016) 399e443
cryoprobe within 5 sec and achieved a tip temperature of <150 C within 10 sec. The device repeatedly generated ice balls of 3 cm diameter in less than 2 minutes. Heat load tissue model studies revealed the generation of a full thickness (8 mm) 2 - e10 cm long cryogenic lesions (probe freeze zone dependent) within 1 min, achieving an opposite surface temperature of <-<100 C. Preliminary animal studies demonstrated the delivery of an ablative cryogenic “dose”, producing a contiguous transmural linear lesion in <90 seconds. These studies demonstrate that the SCN technology provides for rapid, effective, controllable freezing of targeted tissue. The ablative power, speed and directional freeze characteristics of the SCN system also offers the potential of improved safety via a reduction in procedural time compared to current cryoablation devices. Further, these technological developments may open new avenues for the application of cryo to treat other cardiac arrhythmogenic disorders including ventricular tachycardia. S068 A MICRO-THERMAL SENSOR FOR FOCAL THERAPY APPLICATIONS H. Natesan 1, *, W. Hodges 2, L. Tian 3, J. Choi 4, S. Lubner 2, J. Rogers 3, C. Dames 2, J. Bischof 1. 1 University of Minnesota, Minneapolis, Minnesota, United States; 2 University of California, Berkeley, California, United States; 3 University of Illinois, Champaign, Illinois, United States; 4 East Carolina University, Greenville, North Carolina, United States * Corresponding author.
Atrial fibrillation (AF) is an increasingly prevalent and debilitating heart condition. A promising approach to treat AF is cryoablation, or freezing of the pulmonary vein (PV). However, treatment in thin PV (<2 mm) often suffers from over or under-freezing. To address this issue, there is an urgent need to monitor PV contact with balloon catheter, PV thickness, and freeze completion during treatment. Unfortunately, the typical resolution of clinical imaging techniques is too large (~1 mm) to successfully monitor freezing in the PV or other smaller cardiovascular structures (1e2 mm thick). These techniques need to be supplemented with reliable information on freezing within thin tissues at the millimeter to sub millimeter level. Here then we present a response to this need through development of a micro- thermal sensor based on the “3u” technique. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3u” technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of PV. To begin with “3u” sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoablation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode, new measurements related to tissue vs. fluid (i.e., water) contact, fluid flow conditions, tissue thickness, and phase change were made. As an ideal surface for balloons, the sensor has been deposited on a flexible, stretchable polymer substrate and calibrated for tissue measurements. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3u” sensors on in vivo deployed focal therapy probe surfaces (i.e., balloons or catheters). Source of funding: National Science Foundation (CBET Grant #1236760), NSF Graduate Research Fellowship (Grant #1106400), Medtronic Inc. S069 CRYOSURGICAL ABLATION IN THE GASTROINTESTINAL DEVELOPMENT OF A NOVEL CRYOSURGICAL PLATFORM
TRACT:
A. Robilotto 1, *, J. Stewart 1, J.M. Baust 1, R. Van Buskirk 2, A. Gage 3, J.G. Baust 2. 1 CPSI Biotech, Owego, New York, United States; 2 Binghamton University, Institute of Biomedical Technology, Binghamton, New York, United States; 3 State University of New York at Buffalo, Department of Surgery, Buffalo, New York, United States * Corresponding author.
As cryosurgery grows, technological advancements are beginning to allow for the treatment of diseases that were previously beyond the ability of
417
cryoablative platforms. With devices becoming more powerful and probes becoming smaller and more varied in their configurations, cryosurgical treatments are now available for a wide range of diseases including those of the gastrointestinal and urogenital tracts, cardiac and vasculature tissues, and neurons and ganglia within the spinal cord. Recently, we developed a pressurized, sub-cooled nitrogen (PSN) device and associated cryoprobes for the treatment of various diseases and tissues of the gastrointestinal (GI) tract. In this study the performance of two cryoprobes were assessed, a 1.8 mm cryogen spray-probe for treating Barrett’s esophagus and esophageal cancers and an 18 Ga endoscopic ultrasound (EUS) compatible cryoprobe for treating pancreatic cancers. Assessments were made using thermocouple arrays in conjunction with a number of tissue analogs. It was found that the 1.8 mm cryogen spray-probe generated spray temperatures of -20 C in 20 s and -40 C in 35 s, and when held a distance of 3.2 mm above the tissue analog the spray-probe froze to a depth of 1.2 mm after 30 s and 5.8 mm after 180 s. For the 18 Ga endoscopic cryoprobe, iceballs 2.14 cm in diameter were created following 5 min of freezing with a nadir surface temperature below 120 C. Temperature distributions revealed that the -20 C isotherm reached a diameter of 1.87 cm following 5 min of freezing and the -40 C isotherm reached 1.20 cm. The endoscopic cryoprobe was also evaluated in a pilot animal study which served as a proof of concept and verified that the probe was EUS compatible and capable of generating cryolesions in a clinical setting. Although further testing and refinement are needed, these studies demonstrate the viability of the PSN-GI cryoablative platform. The use of this system offers the potential for improved treatment efficacy for a wide range of GI disorders. S070 A NOVEL STRATEGY TO ENHANCE THE CRYOSURGICAL OUTCOME IN GEL PHANTOMS K. Ramajayam 1, *, A. Kumar 2, S. Sarangi 2, A. Thirugnanam 1. 1 National Institute of Technology, Department of Biotechnology and Medical Engineering, Rourkela, Odisha, India; 2 National Institute of Technology, Department of Mechanical Engineering, Rourkela, Odisha, India * Corresponding author.
During cryosurgery, a eutectic adjuvant can enhance the rate of freezing inside the tumour. However, the increment in freezing is detrimental to the healthy tissue neighbouring the tumour. In the present study, a novel combinative strategy is proposed that increases the freezing inside the tissue mimicking agarose gel phantoms and at the same time limits freezing at the desired location by using a low thermal conductivity perfluorocarbon solution at the gel-perfluorocarbon interface. In this current work, cryosurgery has been performed on tissue mimicking agarose gel phantoms (1% (w/v) Agarose, k ¼ 0.541 W/mK) in the absence and presence of a eutectic adjuvant like Glycine (i.e. 0.2%, 1% and 5% (w/v)). Further, an experiment has been carried out to evaluate the efficacy of perfluorocarbon as a barrier to freezing in glycine-agarose gel phantom. The thermal history of freezing is measured using a K-type thermocouple connected to a data acquisition system in an interface with a computer. The results demonstrate that with the increase in the concentration of glycine (from 0.2% to 1% and subsequently to 5% (w/v)) in the gel phantoms, there is an enhancement in freezing during cryosurgery. A comparison between the temperature distribution of 1% (w/v) Agarose gel without glycine and 1% (w/v) Agarose with 5% (w/v) glycine during freezing suggests a substantial decrement in temperature at each thermocouple location. Besides, when gel phantom with 5% (w/v) glycine is cooled in the presence of perfluorocarbon, the results of the temperature profile near the interface and the visual observation of ice ball indicate that the freezing front does not cross the gel-perfluorocarbon interface. In conclusion, this study advocates a novel combinative approach that enhances freezing inside the gel and limits it to the desired location, thus, improving the efficacy of cryosurgery significantly. Source of funding: The authors would like to thank the Department of Biotechnology and Medical Engineering, NIT Rourkela and the Department of Science and Technology(DST), and the Government of India (Project sanction order no. SERC/ET-0449/2012 dated March 4, 2013) for the financial support.
cryoprobe within 5 sec and achieved a tip temperature of <150 C within 10 sec. The device repeatedly generated ice balls of 3 cm diameter in less than 2 minutes. Heat load tissue model studies revealed the generation of a full thickness (8 mm) 2 - e10 cm long cryogenic lesions (probe freeze zone dependent) within 1 min, achieving an opposite surface temperature of <-<100 C. Preliminary animal studies demonstrated the delivery of an ablative cryogenic “dose”, producing a contiguous transmural linear lesion in <90 seconds. These studies demonstrate that the SCN technology provides for rapid, effective, controllable freezing of targeted tissue. The ablative power, speed and directional freeze characteristics of the SCN system also offers the potential of improved safety via a reduction in procedural time compared to current cryoablation devices. Further, these technological developments may open new avenues for the application of cryo to treat other cardiac arrhythmogenic disorders including ventricular tachycardia. S068 A MICRO-THERMAL SENSOR FOR FOCAL THERAPY APPLICATIONS H. Natesan 1, *, W. Hodges 2, L. Tian 3, J. Choi 4, S. Lubner 2, J. Rogers 3, C. Dames 2, J. Bischof 1. 1 University of Minnesota, Minneapolis, Minnesota, United States; 2 University of California, Berkeley, California, United States; 3 University of Illinois, Champaign, Illinois, United States; 4 East Carolina University, Greenville, North Carolina, United States * Corresponding author.
Atrial fibrillation (AF) is an increasingly prevalent and debilitating heart condition. A promising approach to treat AF is cryoablation, or freezing of the pulmonary vein (PV). However, treatment in thin PV (<2 mm) often suffers from over or under-freezing. To address this issue, there is an urgent need to monitor PV contact with balloon catheter, PV thickness, and freeze completion during treatment. Unfortunately, the typical resolution of clinical imaging techniques is too large (~1 mm) to successfully monitor freezing in the PV or other smaller cardiovascular structures (1e2 mm thick). These techniques need to be supplemented with reliable information on freezing within thin tissues at the millimeter to sub millimeter level. Here then we present a response to this need through development of a micro- thermal sensor based on the “3u” technique. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3u” technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of PV. To begin with “3u” sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoablation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode, new measurements related to tissue vs. fluid (i.e., water) contact, fluid flow conditions, tissue thickness, and phase change were made. As an ideal surface for balloons, the sensor has been deposited on a flexible, stretchable polymer substrate and calibrated for tissue measurements. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3u” sensors on in vivo deployed focal therapy probe surfaces (i.e., balloons or catheters). Source of funding: National Science Foundation (CBET Grant #1236760), NSF Graduate Research Fellowship (Grant #1106400), Medtronic Inc. S069 CRYOSURGICAL ABLATION IN THE GASTROINTESTINAL DEVELOPMENT OF A NOVEL CRYOSURGICAL PLATFORM
TRACT:
A. Robilotto 1, *, J. Stewart 1, J.M. Baust 1, R. Van Buskirk 2, A. Gage 3, J.G. Baust 2. 1 CPSI Biotech, Owego, New York, United States; 2 Binghamton University, Institute of Biomedical Technology, Binghamton, New York, United States; 3 State University of New York at Buffalo, Department of Surgery, Buffalo, New York, United States * Corresponding author.
As cryosurgery grows, technological advancements are beginning to allow for the treatment of diseases that were previously beyond the ability of
417
cryoablative platforms. With devices becoming more powerful and probes becoming smaller and more varied in their configurations, cryosurgical treatments are now available for a wide range of diseases including those of the gastrointestinal and urogenital tracts, cardiac and vasculature tissues, and neurons and ganglia within the spinal cord. Recently, we developed a pressurized, sub-cooled nitrogen (PSN) device and associated cryoprobes for the treatment of various diseases and tissues of the gastrointestinal (GI) tract. In this study the performance of two cryoprobes were assessed, a 1.8 mm cryogen spray-probe for treating Barrett’s esophagus and esophageal cancers and an 18 Ga endoscopic ultrasound (EUS) compatible cryoprobe for treating pancreatic cancers. Assessments were made using thermocouple arrays in conjunction with a number of tissue analogs. It was found that the 1.8 mm cryogen spray-probe generated spray temperatures of -20 C in 20 s and -40 C in 35 s, and when held a distance of 3.2 mm above the tissue analog the spray-probe froze to a depth of 1.2 mm after 30 s and 5.8 mm after 180 s. For the 18 Ga endoscopic cryoprobe, iceballs 2.14 cm in diameter were created following 5 min of freezing with a nadir surface temperature below 120 C. Temperature distributions revealed that the -20 C isotherm reached a diameter of 1.87 cm following 5 min of freezing and the -40 C isotherm reached 1.20 cm. The endoscopic cryoprobe was also evaluated in a pilot animal study which served as a proof of concept and verified that the probe was EUS compatible and capable of generating cryolesions in a clinical setting. Although further testing and refinement are needed, these studies demonstrate the viability of the PSN-GI cryoablative platform. The use of this system offers the potential for improved treatment efficacy for a wide range of GI disorders. S070 A NOVEL STRATEGY TO ENHANCE THE CRYOSURGICAL OUTCOME IN GEL PHANTOMS K. Ramajayam 1, *, A. Kumar 2, S. Sarangi 2, A. Thirugnanam 1. 1 National Institute of Technology, Department of Biotechnology and Medical Engineering, Rourkela, Odisha, India; 2 National Institute of Technology, Department of Mechanical Engineering, Rourkela, Odisha, India * Corresponding author.
During cryosurgery, a eutectic adjuvant can enhance the rate of freezing inside the tumour. However, the increment in freezing is detrimental to the healthy tissue neighbouring the tumour. In the present study, a novel combinative strategy is proposed that increases the freezing inside the tissue mimicking agarose gel phantoms and at the same time limits freezing at the desired location by using a low thermal conductivity perfluorocarbon solution at the gel-perfluorocarbon interface. In this current work, cryosurgery has been performed on tissue mimicking agarose gel phantoms (1% (w/v) Agarose, k ¼ 0.541 W/mK) in the absence and presence of a eutectic adjuvant like Glycine (i.e. 0.2%, 1% and 5% (w/v)). Further, an experiment has been carried out to evaluate the efficacy of perfluorocarbon as a barrier to freezing in glycine-agarose gel phantom. The thermal history of freezing is measured using a K-type thermocouple connected to a data acquisition system in an interface with a computer. The results demonstrate that with the increase in the concentration of glycine (from 0.2% to 1% and subsequently to 5% (w/v)) in the gel phantoms, there is an enhancement in freezing during cryosurgery. A comparison between the temperature distribution of 1% (w/v) Agarose gel without glycine and 1% (w/v) Agarose with 5% (w/v) glycine during freezing suggests a substantial decrement in temperature at each thermocouple location. Besides, when gel phantom with 5% (w/v) glycine is cooled in the presence of perfluorocarbon, the results of the temperature profile near the interface and the visual observation of ice ball indicate that the freezing front does not cross the gel-perfluorocarbon interface. In conclusion, this study advocates a novel combinative approach that enhances freezing inside the gel and limits it to the desired location, thus, improving the efficacy of cryosurgery significantly. Source of funding: The authors would like to thank the Department of Biotechnology and Medical Engineering, NIT Rourkela and the Department of Science and Technology(DST), and the Government of India (Project sanction order no. SERC/ET-0449/2012 dated March 4, 2013) for the financial support.