H-FIRE Pulse Timing to Reduce Arcing and Muscle Stimulation
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Solution Overview
Problem
Existing pulsed electric field treatments for tissue ablation, such as high-frequency irreversible electroporation (H-FIRE), face challenges with high lethal electric field thresholds, muscle contractions, bubble formation, and electrical arcing, which complicate clinical applications and reduce efficacy.
Innovation Solution
The method involves administering bursts of bipolar or monopolar electrical pulses with controlled interphase and interpulse delays to minimize bubble formation and arcing, while maintaining effective tissue ablation and reducing muscle stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If long monopolar pulses (70-100 μs) are used for tissue ablation, then effective tissue destruction is achieved, but muscle contractions and cardiac arrhythmias occur due to stimulation of excitable cells
Solution Approach 1:
The long monopolar pulse is segmented into multiple short bipolar pulses (1-10 μs each) delivered in bursts. Each bipolar pulse consists of a positive phase followed by a negative phase with an interphase delay (d1). This segmentation allows the negative phase to repolarize excitable cells before the next positive phase, preventing sustained muscle contraction while maintaining cumulative electroporation effect for tissue ablation.
Solution Approach 2:
The treatment uses periodic bursts of bipolar pulses with controlled interpulse delays (d2) between bursts. The periodic delivery at high frequency (e.g., 100 Hz) within bursts, combined with longer intervals between bursts, creates a temporal pattern that achieves effective energy delivery for ablation while allowing recovery periods that prevent continuous muscle stimulation and arrhythmias.
2Reliability
If high voltage is applied to achieve effective ablation, then tissue destruction is improved, but electrical arcing and bubble formation increase
Solution Approach 1:
The use of periodic burst patterns with interpulse delays allows bubbles formed during one pulse to partially dissipate before the next pulse arrives. The high-frequency delivery within bursts maintains effective energy deposition, while the longer intervals between bursts reduce cumulative bubble formation and associated arcing risks, enabling safe operation at higher voltages.
Solution Approach 2:
The invention changes multiple parameters simultaneously: pulse width (shorter 1-10 μs), polarity (bipolar alternating), timing (controlled d1 and d2 delays), and burst structure. These parameter changes collectively reduce the likelihood of electrical breakdown and bubble-mediated arcing while preserving ablation efficacy through cumulative electroporation.
3Reliability
If high amplitude electric fields are used for irreversible electroporation, then complete cell membrane permeabilization is achieved, but the lethal electric field threshold increases requiring higher energy dosages
Solution Approach 1:
The high-frequency bipolar pulses within each burst create preliminary electroporation effects that increase membrane permeability before the next burst arrives. The interpulse delay allows partial recovery and redistribution of charge, preparing cells for subsequent pulses. This preliminary action across multiple bursts achieves complete permeabilization at lower individual pulse amplitudes, reducing total energy requirements compared to single high-amplitude pulses.
Solution Approach 2:
The continuous delivery of bipolar pulse bursts maintains cumulative electroporation effect throughout the treatment duration. The high repetition rate within bursts ensures continuous membrane stress without complete recovery, while the burst structure prevents excessive heating. This continuous useful action achieves irreversible electroporation more efficiently than intermittent long pulses, reducing overall energy dosage.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for precise control over biological outcomes, reducing unwanted effects like muscle contractions and arcing, enabling safer and more predictable tissue ablation with lower energy dosages and potentially eliminating the need for neuromuscular blocking agents.
Implementation Method 1
Electroporation is a biological phenomenon in which cells exhibit increased membrane permeability upon exposure to high amplitude electric fields
Implementation Method 2
This is due to the local repolarization that occurs with each negative phase prior to activation of the minimum number of voltage-gated sodium channels (VGSCs) required for excitation
Implementation Method 3
management of patients receiving IRE can be difficult. The long (70-100 μs) pulses of conventional IRE easily stimulate cardiac myocytes, pain receptors, and skeletal muscle fibers, resulting in muscle contractions and potential arrhythmias
Data Source
AI summary
High-frequency irreversible electroporation (H-FIRE) is a tissue ablation modality employing bursts of electrical pulses in a positive phase-interphase delay-negative phase-interpulse delay pattern. Despite accumulating evidence suggesting the significance of these delays, their effects on therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been studied extensively. The present invention provides methods of pulse delivery, including delays, that mitigate bubble formation and/or minimize the risk of arcing, such as due to the presence of bubbles, and/or minimize muscle stimulation are described herein.