Thermal Analysis of Infrared Irradiation-Assisted Nanosecond-Pulsed Tumor Ablation

Nanosecond Pulsed Electric Fields (nsPEF) have the potential to treat a variety of cancer types including melanoma, pancreatic and lung squamous cancers. Recent studies show that nsPEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. A feedbacklooped heating system, utilizing a 980-nm fiber optic laser, was integrated into nsPEF electrodes for tumor ablation. The laser beam profile was determined to be Gaussian using a knife-edge technique. Thermal properties of the biological target were evaluated based on the treatment area, penetration depth and thermal distribution due to laser irradiation with or without nsPEF. Synergistic effects between nsPEF and the moderately elevated temperature at the target was observed, resulting in enhanced overall survival tumor regression up to 50% in the treatment of lung squamous cell cancer in mice

Thermally Assisted Pulsed Electric Field Ablation for Cancer Therapy

Pulsed Electric Fields (PEF) have promised improved treatment results in a variety of cancer types including melanoma, pancreatic and lung squamous cancer. Recent studies show that PEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. Experiments were performed to design, calibrate and implement a feedback-looped infrared laser irradiation system that could maintain specified temperatures during the treatment. The exact treatment area, penetration depth and thermal distribution of a 980-nm laser fiber were quantified using several methods, including the knife-edge technique and a tissue optical property study. In vivo and in vitro experiments using this protocol show that there is a synergistic effect between PEF and the moderately elevated heating of a target, which resulted in an increased overall treatment area up to a factor of 5.6 in vitro as well as an increased the overall survival of the mice by 54% in the treatment of pancreatic cancer in mice

Synergistic Effect of Subnanosecond Pulsed Electric Fields and Temperature on the Viability of Biological Cells

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with electric field strengths below 100 kV/cm, pulse numbers on the order of 106 would be needed to achieve similar effects. In this dissertation, it was shown that the energy density required for cell death can be reduced considerably if the temperature of the sample is increased to values above physiological temperature (37°C). In order to perform the experiments, a solution of biological sample (growth medium and Hepa 1-6 cells) was exposed to 200 ps pulses in which the electric field strength ranged from 60 kV/cm to 100 kV/cm and the pulse number ranged between 100 and 3,300 pulses. The temperature of the sample was controlled externally by placing the exposure chamber in a controlled temperature environment, and was varied between room temperature and 47°C. In order to reduce the thermal effects due to ohmic heating from the pulses, the repetition rate of the pulses was kept below 10 Hz. The effect, cell death, was determined by trypan blue uptake of the cells 4 hours after experimental exposure. The pulse generator used was an 8 stage Marx bank in which the output pulse was formed with a peaking and tailcut switch. The peaking switch was used to decrease the risetime of the output pulse to less than 200 ps, and the tailcut switch was used to cut off the decaying portion of the pulse. The eight spark gap switches of the Marx bank were pressurized with Nitrogen, while both the peaking and tailcut switch operated in air at atmospheric pressure. The output voltage of the pulse generator ranged from 10 kV to 20 kV and the pulse width could be varied between 140 ps and 230 ps. A conical exposure chamber was designed to expose the biological sample to the pulsed voltages, such that the electric field across the gap was homogeneous. The voltage was measured with a capacitive voltage divider, which was incorporated into the cable leading to the load. The results indicate that an increase in temperature above 37°C caused the cells to be more susceptible to the pulsed electric fields. The lethality increased to over 25% (trypan blue uptake) when the cells were exposed to 2,000 pulses with an electric field strength of 78 kV/cm at 47°C. For temperatures at and below 37°C, there was no indication of cell death, when compared to the controls, for the same pulsing conditions. In order to determine the reason for this increase in cell lethality due to the pulsed electric fields with an increase in temperature, the electrical properties of HELA 1-6 cells were measured by means of time domain reflective spectroscopy. The conductivity of the growth medium, plasma membrane, and cytoplasm increased with temperature. The permittivity of the medium and membrane increased, while the permittivity of the cytoplasm decreased with temperature. Using this data and comparing the results of the trypan blue studies, it seems to be likely that the subanosecond pulse induced cell death can be considered a dose effect with respect to the energy deposited in the cell membrane. Assuming that subcellular membranes show a similar temperature dependence in their electrical properties, the possibility that the cell lethality is triggered through permeabilization of inner membranes (in addition to that of the plasma membrane) cannot be excluded. The threshold voltage across the membrane required for electropermeabilization was shown to decrease with an increase in temperature, which likely due to the increase in the membrane fluidity with temperature. This argument is supported by molecular dynamics simulations which show an increased probability for pore formation with temperature. Based on a three layer (medium, membrane, cytoplasm) cell model and using the dielectric spectroscopy results it was concluded that the induced membrane voltage also decreases with an increase in temperature. Consequently, the threshold voltage needed to induce electropermeabilization must decrease at a faster rate than the induced membrane voltage from the electric field

Annual Research Report, 2010-2011

Annual report of collaborative research projects of Old Dominion University faculty and students in partnership with business, industry and government.https://digitalcommons.odu.edu/or_researchreports/1000/thumbnail.jp