Browsing by Author "O'Brien, Timothy J."
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- The Application of BioHeat Perfusion Sensors to Analyze Preservation Temperature and Quantify Pressure Ischemia of Explanted OrgansO'Brien, Timothy J. (Virginia Tech, 2015-03-09)The development of an organ preservation system (primarily kidneys and livers, but could be adapted to fit hearts, lungs, and even limbs in the future) that can provide surgeons and doctors with real-time quantitative feedback on the health of the organ would be a significant improvement on current transplant practices. This organ transport system will provide surgeons and doctors the opportunity to make more educated decisions towards whether or not to proceed with organ transplantation. Here, we discuss the use Smart Perfusion's organ preservation system as a platform for determining the optimal perfusion temperature of an organ. Porcine kidneys were procured and perfused with a modified PBS solution on the Vasowave™. While on this organ preservation system, a heart emulating pressure waveform (90/50 mmHg) was generated and sent to the specimen. The pressure response, flow rate, temperature, pH, dissolved oxygen content, and conductivity of the fluid stream were all monitored throughout the duration of experimentation. In addition to inline sensors, IR imaging captured the surface temperature of the organ while on the system. Lastly, the use of a combined heat flux-temperature (CHFT) sensor, previously developed at Virginia Tech, was applied for the first time to monitor and measure local tissue perfusion of an explanted organ. A total of 12 experiments were performed (6 at a set fluid temperature of 15°C, and 6 at 20°C). All system data was collected, statistically evaluated and finally compared against blind histological readings (taken at the termination of each experiment at the hilum and pole) to investigate the effects of temperature on organ vasculature. The results of this experiment indicated that the effects of temperature on explanted kidneys can be affectively measured using a non-invasive bioheat perfusion sensor. Specifically, the lower temperature group of kidneys was measured to have lower perfusion. Furthermore, an enhancement to the CHFT sensor technology (CHFT+) was developed and tested for compliance. A controllable thin filmed heat resistor was added to the CHFT assembly to replace the current convective thermal event. This enhancement improved the measured heat flux and temperature signals and enables autonomy. Also, the thin and semi-flexible nature of the new CHFT+ sensor allows for perfusion measurements to be taken from the underside of the organ, permitting a quantitative measure of pressure ischemia. Results from a live tissue test illustrated, for the first time, the effects of pressure ischemia on an explanted porcine kidney.
- High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular CarcinomaPartridge, Brittanie R.; O'Brien, Timothy J.; Lorenzo, Melvin F.; Coutermarsh-Ott, Sheryl; Barry, Sabrina L.; Stadler, Krystina L.; Muro, Noelle; Meyerhoeffer, Mitchell; Allen, Irving C.; Davalos, Rafael V.; Dervisis, Nikolaos G. (2020-03)Purpose: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. Materials and Methods: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. Results: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3(+)/CD4(-)/CD8(-) lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm(3) +/- 0.74 and 1.56 cm(3) +/- 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm +/- 28.2 and 957 V/cm +/- 24.4 V/cm (P = .0004). Conclusions: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.
- An Investigation of Thermal Mitigation Strategies for Electroporation-Based TherapiesO'Brien, Timothy J. (Virginia Tech, 2019-07-16)Irreversible electroporation (IRE) is an energy directed focal ablation technique. This procedure typically involves the placement of two or more electrodes into, or around, a region of interest within the tissue and administering a sequence of short, intense, pulsed electric fields (PEFs). The application of these PEFs results in an increase in the transmembrane potential of all cells within the electric field above a critical value, destabilizing the lipid bilayer of the cellular membrane and increasing the cell-tissue permeability. For years, many have used this phenomenon to assist the transport of macromolecules typically unable to penetrate the cell membrane with the intent of avoiding cell necrosis or irreversible electroporation. More recently, however, irreversible electroporation has proven to be a successful alternative for the treatment of cancer. Proper tuning of the pulse parameters has allowed for a targeted treatment of localized tumors, and has shown immense value in the treatment of surgically inoperable tumors located near major blood vessels and nerves. While it is critical to ensure sufficient treatment of the target tissue, it can be equally vital to the treatment and patients overall outcome that the pulsing conditions are set to moderate the associated thermal effects with the electroporation of biological tissue. The development of thermal mitigation strategies for IRE treatment is the focus of this dissertation. Herein, the underlying theory and thermal considerations of tissue electroporation in various scenarios are described. Additionally, new thermal mitigation approaches with the intention of maintaining tissue temperature below a thermally damaging threshold, while also preserving or improving IRE lesion volume are detailed. Further, numerical models were developed and ex vivo tissue experiments performed using a perfused organ model to examine three thermal mitigation strategies in their ability to moderate temperature. Tests conducted using thermally mitigating treatment delivery on live tissue confirm the capacity to deliver more energy to the tissue at a thermally acceptable temperature, and provide the potential for a replete IRE lesion.
- Pangolins in global camera trap data: Implications for ecological monitoringKhwaja, Hannah; Buchan, Claire; Wearn, Oliver R.; Bahaa-el-din, Laila; Bantlin, Drew; Bernard, Henry; Bitariho, Robert; Bohm, Torsten; Borah, Jimmy; Brodie, Jedediah; Chutipong, Wanlop; du Preez, Byron; Ebang-Mbele, Alex; Edwards, Sarah; Fairet, Emilie; Frechette, Jackson L.; Garside, Adrian; Gibson, Luke; Giordano, Anthony; Gopi, Govindan Veeraswami; Granados, Alys; Gubbi, Sanjay; Harich, Franziska; Haurez, Barbara; Havmoller, Rasmus W.; Helmy, Olga; Isbell, Lynne A.; Jenks, Kate; Kalle, Riddhika; Kamjing, Anucha; Khamcha, Daphawan; Kiebou-Opepa, Cisquet; Kinnaird, Margaret; Kruger, Caroline; Laudisoit, Anne; Lynam, Antony; Macdonald, Suzanne E.; Mathai, John; Sienne, Julia Metsio; Meier, Amelia; Mills, David; Mohd-Azlan, Jayasilan; Nakashima, Yoshihiro; Nash, Helen C.; Ngoprasert, Dusit; Nguyen, An; O'Brien, Timothy J.; Olson, David; Orbell, Christopher; Poulsen, John; Ramesh, Tharmalingam; Reeder, DeeAnn; Reyna, Rafael; Rich, Lindsey N.; Rode-Margono, Johanna; Rovero, Francesco; Sheil, Douglas; Shirley, Matthew H.; Stratford, Ken; Sukumal, Niti; Suwanrat, Saranphat; Tantipisanuh, Naruemon; Tilker, Andrew; Van Berkel, Tim; Van der Weyde, Leanne K.; Varney, Matthew; Weise, Florian; Wiesel, Ingrid; Wilting, Andreas; Wong, Seth T.; Waterman, Carly; Challender, Daniel W. S. (2019-10)Despite being heavily exploited, pangolins (Pholidota: Manidae) have been subject to limited research, resulting in a lack of reliable population estimates and standardised survey methods for the eight extant species. Camera trapping represents a unique opportunity for broad-scale collaborative species monitoring due to its largely nondiscriminatory nature, which creates considerable volumes of data on a relatively wide range of species. This has the potential to shed light on the ecology of rare, cryptic and understudied taxa, with implications for conservation decision-making. We undertook a global analysis of available pangolin data from camera trapping studies across their range in Africa and Asia. Our aims were (1) to assess the utility of existing camera trapping efforts as a method for monitoring pangolin populations, and (2) to gain insights into the distribution and ecology of pangolins. We analysed data collated from 103 camera trap surveys undertaken across 22 countries that fell within the range of seven of the eight pangolin species, which yielded more than half a million trap nights and 888 pangolin encounters. We ran occupancy analyses on three species (Sunda pangolin Manis javanica, white-bellied pangolin Phataginus tricuspis and giant pangolin Smutsia gigantea). Detection probabilities varied with forest cover and levels of human influence for P. tricuspis, but were low (<0.05) for all species. Occupancy was associated with distance from rivers for M. javanica and S. gigantea, elevation for P. tricuspis and S. gigantea, forest cover for P. tricuspis and protected area status for M. javanica and P. tricuspis. We conclude that camera traps are suitable for the detection of pangolins and large-scale assessment of their distributions. However, the trapping effort required to monitor populations at any given study site using existing methods appears prohibitively high. This may change in the future should anticipated technological and methodological advances in camera trapping facilitate greater sampling efforts and/or higher probabilities of detection. In particular, targeted camera placement for pangolins is likely to make pangolin monitoring more feasible with moderate sampling efforts. (c) 2019 The Authors. Published by Elsevier B.V.