Abstract
Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength–duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.
Highlights
Treatments with intense pulsed electric fields (PEF) are central for many existing and emerging medical applications, including tumor and tissue ablations [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
The stimulation was considered to be at the threshold when it evoked a minimally discernable compound action potential (CAP), with a peak amplitude of about 20 mV (Figure 1A)
0.5-mm diameter needles were immersed in the solution in a plane orthogonal to the nerve, either touching it or at a distance3. oTf h18e stimulation was considered to be at the threshold when it evoked a minimally discernable compound action potential (CAP), with a peak amplitude of about 20 mV (Figure 1A)
Summary
Treatments with intense PEF are central for many existing and emerging medical applications, including tumor and tissue ablations [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. PEF ablations are considered minimally invasive, the treatment may cause severe pain, involuntary muscle contractions, and heart fibrillation [7,16,17,18]. These major side effects need to be mitigated by local or general anesthesia and muscle relaxants, as well as by synchronizing PEF with nonvulnerable phases of the heart cycle. These side effects can be better appreciated by comparing the induced transmembrane potentials (TMP) for neuromuscular excitation and for electroporation. With the stimulation TMP thresholds being an order of magnitude smaller than the TMP required for ablation, the stimulated tissue volume is often much larger than the ablation volume
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