Targeted Tissue Ablation With Nanosecond Pulses
ABSTRACT In-vivo porcine studies on the effect of nanosecond high-voltage pulses on liver tissue have shown that cell death can be induced in well-defined tissue volumes without damaging collagen-predominant structures. Comparison of the experimental results with the results of a 3-D finite element model allowed us to determine the threshold electric field for cell death. For 30, 100-ns-long pulses this was found to be in the range from 12 to 15 kV/cm. Modeling of the temperature distribution in the tissue using Pennes' bioheat equation showed that the lethal effect of nanosecond pulses on cells is nonthermal. Muscle contractions, generally caused by high-voltage pulses, were significantly reduced for the 100-ns pulses compared to microsecond-long pulses. The results of these studies indicate that high-voltage nanosecond pulses reliably kill normal liver cells in vivo, and therefore, may be useful for liver tumor treatments.
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ABSTRACT: We report on an experimental study of the temporal evolution of OH density and gas temperature in spark discharges created by nanosecond repetitively pulsed discharges in pure water vapour at 475 K and atmospheric pressure. The plasma was generated by 20 kV, 20 ns pulses, at a repetition frequency of 10 kHz. The temperature was measured during the discharge by optical emission spectroscopy of the second positive system of N2, and between two discharges by two-colour OH-planar laser induced fluorescence (OH-PLIF) using two pairs of rotational transitions. Between two successive discharges, the relative density of OH was measured by OH-PLIF and was found to decay very slowly, with a 1/e decay time of about 50 µs. With the use of a chemical kinetics model, the OH density was placed on an absolute scale.Journal of Physics D Applied Physics 02/2014; 47:075204. DOI:10.1088/0022-3727/47/7/075204 · 2.52 Impact Factor
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ABSTRACT: Strategies for treating liver cancer using radiation, chemotherapy combinations and tyrosine kinase inhibitors targeting specific mutations have provided longer survival times, yet multiple treatments are often needed and recurrences with new malignant phenotypes are not uncommon. New and innovative treatments are undoubtedly needed to successfully treat liver cancer. Over the last decade, nanosecond pulsed electric fields (nsPEFs) have shown promise in pre-clinical studies; however, these have been limited to treatment of skin cancers or xenographs in mice. In the present report, an orthotopic hepatocellular carcinoma (HCC) model is established in rats using N1-S1 HCC cells. Data demonstrate a response rate of 80-90% when 1000 pulses are delivered with 100ns durations, electric field strengths of 50kV/cm and repetition rates of 1Hz. N1-S1 tumours treated with nsPEFs expressed significant number of cells with active caspase-3 and caspase-9, but not caspase-8, indicating an intrinsic apoptosis mechanism(s) as well as caspase-independent mechanisms. Most remarkably, rats with successfully ablated tumours failed to re-grow tumours when challenged with a second injection of N1-S1 cells when implanted in the same or different liver lobe that harboured the original tumour. Given this protective effect, infiltration of immune cells and the presence of granzyme B expressing cells within days of treatment suggest the possibility of an anti-tumour adaptive immune response. In conclusion, NsPEFs not only eliminate N1-S1 HCC tumours, but also may induce an immuno-protective effect that defends animals against recurrences of the same cancer.European journal of cancer (Oxford, England: 1990) 07/2014; 50(15). DOI:10.1016/j.ejca.2014.07.006 · 4.82 Impact Factor
Journal of Nanomedicine & Nanotechnology 01/2013; 04(02). DOI:10.4172/2157-7439.1000163 · 5.72 Impact Factor