Fourier analysis spectroscopy for monitoring tissue impedance changes and treatment outcome during electroporation-based-therapies
Inventors
Lorenzo, Melvin F. • ARENA, Christopher B. • Bhonsle, Suyashree • White, Natalie • EPSHTEYN, LUCY • Davalos, Rafael V.
Assignees
Virginia Tech Intellectual Properties Inc • Angiodynamics Inc
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Publication Number
US-12214189-B2
Publication Date
2025-02-04
Expiration Date
Abstract
Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue, resulting in changes in passive electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time (˜10 s); this timeframe is much larger than pulse periods used with EBTs (˜1 s). Fourier Analysis SpecTroscopy (FAST) is introduced as a methodology for monitoring tissue inter-burst impedance (diagnostic FAST) and intra-burst impedance (therapeutic FAST) during EBTs. FAST is a rapid-capture (<<1 s) technique which enables monitoring of inter-burst and intra-burst impedance during EBTs in real-time. FAST identified a frequency which delineates thermal effects from electroporation effects in measured impedance. Significance: FAST demonstrates the potential to perform EIS, in addition to intra-burst impedance spectroscopy, using existing pulse generator topologies.
Core Innovation
The invention provides Fourier Analysis SpecTroscopy (FAST) for real-time impedance spectroscopy during electroporation-based therapies. It separates diagnostic impedance measurements from therapeutic impedance measurements by using low-voltage diagnostic inter-burst impedance measurements and high-voltage therapeutic intra-burst impedance measurements.
FAST extracts impedance spectra quickly using FFT-based analysis over a wide frequency range during ongoing pulse administration. It identifies a frequency that separates thermal/Joule-heating effects from electroporation effects, enabling impedance-spectrum-based monitoring rather than relying on a single impedance value.
The approach includes a monitoring workflow in which reference impedance measurements or spectra are obtained and impedance changes are identified by measuring inter-burst and intra-burst impedance. It uses the measured impedance spectrum to define a pulsing endpoint when the impedance spectrum flattens (saturates), and it supports temperature-aware pausing, halting, and continuation based on the impedance-derived temperature behavior and electroporation-related spectral behavior.
Claims Coverage
Two independent claims define impedance monitoring during administration of electrical pulses using reference impedance measurements or spectra, identification of impedance changes from inter-burst and intra-burst impedance, and endpoint-driven control that adjusts, stops, halts, and/or continues administration. Across the independent claims, the inventive features include inter-burst/intra-burst impedance monitoring with endpoint determination from impedance change and a high-frequency irreversible electroporation burst scheme with defined frequency monitoring and discrete Fourier transform analysis.
Inter-burst and intra-burst impedance monitoring for endpoint control
Administering a plurality of electrical pulses to a material or a tissue; obtaining a reference impedance measurement or spectrum relating to the material or tissue; identifying any change in impedance relative to the reference impedance measurement or spectrum by measuring inter-burst and intra-burst impedance; and monitoring the administering to determine if a desired endpoint is reached as indicated by the change in impedance, and adjusting one or more parameters, stopping, halting, and/or continuing the administering based on the monitoring.
High-frequency irreversible electroporation burst scheme with DFT impedance analysis
Administering high-voltage bursts of electrical pulses to a material or a tissue using a high-frequency irreversible electroporation burst scheme; obtaining a reference impedance measurement or spectrum relating to the material or tissue; identifying any change in impedance, at a frequency in the range of 18.3 kHz to 2 MHz, relative to the reference impedance measurement or spectrum; monitoring tissue response by monitoring high-voltage inter-pulse, intra-pulse, intra-burst, and/or inter-burst impedance by capturing voltage and current and performing discrete Fourier transform analysis to determine if a desired endpoint is reached as indicated by the change in impedance; and adjusting one or more parameters of, stopping, halting, and/or continuing the administering based on the monitoring.
The claim set covers monitoring administration of electrical pulses using impedance references and impedance-change detection across inter-burst and intra-burst intervals, with endpoint-triggered control actions. The narrower independent claim further constrains monitoring to high-frequency irreversible electroporation burst schemes and defines a frequency range and discrete Fourier transform analysis of captured voltage and current impedance data.
Stated Advantages
Enables monitoring to determine if a desired endpoint is reached as indicated by the change in impedance.
Supports adjusting, stopping, halting, and/or continuing the administering based on the monitoring.
Enables differentiation of thermal/Joule-heating effects from electroporation effects by identifying a frequency that separates them.
Documented Applications
Real-time impedance spectroscopy for monitoring electroporation-based therapies by separating diagnostic inter-burst impedance measurements from therapeutic intra-burst impedance measurements.
Monitoring and defining a pulsing endpoint when the impedance spectrum flattens (saturates) during electroporation-based therapy administration.
Using impedance-spectrum flattening and recovery patterns to relate impedance changes to electroporation outcomes and cell death outcomes such as irreversible or reversible electroporation, cell lysis, necrosis, or apoptosis.
Validation of impedance spectroscopy on potato tissue against a commercial potentiostat, and needle-electrode ablation experiments where impedance changes correlate with ablation extent and impedance/temperature relationships.
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