TREATMENT PLANNING FOR ELECTROPORATION-BASED THERAPIES

• US 20110106221A1
• Filed: 10/18/2010
• Published: 05/05/2011
• Est. Priority Date: 04/29/2008
• Status: Active Grant

• Current Assignee: Virginia Tech Intellectual Properties, Inc. (Virginia Polytechnic Institute and State University)
• Original Assignee: Virginia Tech Intellectual Properties, Inc. (Virginia Polytechnic Institute and State University)
• Inventors: Rossmeisl, John H., Robertson, John L., Neal, Robert E. II, Garcia, Paulo A., Davalos, Rafael V.
• Granted Patent: US 9,198,733 B2
• Time in Patent Office: Days
• US Class Current: 607/74
• CPC Class Codes: A61B 18/12 by passing a current through the tissue to be heated, e.g. high-frequency current
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation
• CPC Class Codes: A61B 2034/104 Modelling the effect of the tool, e.g. the effect of an implanted prosthesis or for predicting the effect of ablation or burring
• CPC Class Codes: A61B 2034/105 Modelling of the patient, e.g. for ligaments or bones
• CPC Class Codes: A61B 34/10 Computer-aided planning, simulation or modelling of surgical operations
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

The present invention provides systems, methods, and devices for electroporation-based therapies (EBTs). Embodiments provide patient-specific treatment protocols derived by the numerical modeling of 3D reconstructions of target tissue from images taken of the tissue, and optionally accounting for one or more of physical constraints or dynamic tissue properties. The present invention further relates to systems, methods, and devices for delivering bipolar electric pulses for irreversible electroporation exhibiting reduced or no damage to tissue typically associated with an EBT-induced excessive charge delivered to the tissue.

Claims

1. A treatment planning system for determining a patient-specific electroporation-based treatment protocol comprising:

a processing module operably configured for performing the following stages;

receiving and processing information from medical images of a target structure and preparing a 3-D reconstruction model of the target structure;

performing a numerical model analysis using as inputs in the analysis the 3-D reconstruction and information from one or more of physical constraints, tissue heterogeneities, dynamic effects of electropermeabilization, dynamic thermal effects, or effects resulting from multiple treatments; and

constructing one or more protocols each providing a treatment region with parameters for electroporating the target structure; and

a processor for executing the stages of the processing module.

2. The treatment planning system of claim 1, wherein the processing module is capable of performing the stages in real time.

3. The treatment planning system of claim 1, wherein the information from medical images is extracted from an array of images obtained from one or more imaging modalities chosen from radiographs, tomography, nuclear scintigraphy, CT, MRI, fMRI, PET, or US.

4. The treatment planning system of claim 1, wherein the numerical model analysis comprises finite element modeling (FEM).

5. The treatment planning system of claim 1, wherein the 3D reconstruction is a surface or a solid volume.

6. The treatment planning system of claim 4, wherein the target structure is a targeted region or mass;

or is a targeted region or mass with neighboring regions;

or is a 3D map of voxels to be treated as independent elements in the finite modeling software.

7. The treatment planning system of claim 1, wherein the numerical model analysis involves accounting for physical constraints, tissue heterogeneities, dynamic effects of electropermeabilization, dynamic thermal effects, and multiple-treatment effects.

8. The treatment planning system of claim 1, further comprising a self-optimization algorithm for constructing the protocols.

9. The treatment planning system of claim 8, wherein the self-optimization algorithm is capable of repeatedly evaluating one or more of physical constraints, placement of electrodes, electric field distribution simulations, and outcome success of the, and evaluation of outcome success until one or more effective protocol is constructed.

10. The treatment planning system of claim 1, wherein the treatment region and parameters for electroporating are determined automatically, interactively, or automatically and interactively with or without user input.

11. The treatment planning system of claim 1, capable of constructing protocols for an initial patient treatment or retreatment with or without additional medical images.

12. The treatment planning system of claim 1, further adapted for instructing an electrical waveform generator to perform the protocol.

13. The treatment planning system of claim 12, further comprising an electrical waveform generator in operable communication with the processing module and capable of receiving and executing the treatment protocol.

14. The treatment planning system of claim 12, wherein instructing comprises specifying a number of bipolar pulses to be delivered, a length of pulse duration at any pole, and a length of any delay between pulses.

15. The treatment planning system of claim 13, wherein the generator is operably configured for delivering a bipolar pulse train.

16. The treatment planning system of claim 2, wherein the processing module further comprises functionality for monitoring electrode or tissue temperature in real time and for considering electrode or tissue temperature in the analysis.

17. A treatment planning method comprising:

receiving and processing information from medical images of a target structure and preparing a 3-D reconstruction model of the target structure;

performing a numerical model analysis using as inputs in the analysis the 3-D reconstruction and information from one or more of physical constraints, tissue heterogeneities, dynamic effects of electropermeabilization, dynamic thermal effects, or effects resulting from multiple treatments;

and constructing an electroporation protocol based on results of the analyzing;

wherein the receiving, processing, analyzing, and constructing is performed in real time.

18. A method of reducing adverse effects of irreversible electroporation comprising administering electrical pulses through electrodes to tissue in a manner which causes irreversible electroporation of the tissue but minimizes electrical charge build up on the electrodes, or minimizes charge delivered to the tissue, or both.

19. The method of claim 18, wherein the adverse effects are one or more of thermal damage of the tissue or electrolysis.

20. The method of claim 19, wherein the electrical pulses comprise a series of unipolar or bipolar pulses with a net charge of zero.

21. The method of claim 20, wherein the net charge of zero is achieved by a change in potential direction between each pulse, or a change in potential direction within each pulse.

22. The method of claim 20, wherein the electrical pulses together comprise a pulse protocol comprising a train of unipolar pulses followed by a train of unipolar pulses of opposite polarity, or a train of bipolar pulses, or simultaneous unipolar pulses of opposite polarity which are offset from one another by a desired amount, or a combination of protocols.

23. The method of claim 22, wherein the electrical pulses have a waveform which is square, triangular, trapezoidal, exponential decay, sawtooth, sinusoidal, or of alternating polarity, or comprise a combination of one or more waveform.

24. A control system for an electroporation device comprising:

a processor in operable communication with a control module;

a control module executable by the processor and in operable communication with an electrical circuit, wherein the control module is operably configured for initiating switching of the circuit at a rate of between 10 ms to 1 ns; and

an electrical circuit operably configured to enable delivery of a voltage to an electrode and switching of the voltage to a second electrode to cause reversing of the polarity of the electric potential between the two electrodes.

25. A electroporation system comprising:

an electroporation device capable of delivering a first unipolar electrical pulse;

the electroporation device further capable of, or a second electroporation device capable of, delivering a second unipolar electrical pulse which is opposite in polarity to the first unipolar pulse;

a processor in operable communication with a control module;

a control module executable by the processor and in operable communication with the electroporation device(s), wherein the control module is operably configured for initiating delivery of the first unipolar electrical pulse at a time 1 and for initiating delivery of the second unipolar electrical pulse at time 2 offset from time 1 by 1 second to 1 nanosecond.

26. An electroporation device operably configured to enable delivery of an electrical pulse to a first electrode, switching of the pulse to a second electrode to cause reversing of the polarity of the electric potential between the two electrodes, and switching of the pulse back to the first electrode or to zero, wherein a cycle of switching is established which cycle is capable of being performed at a rate of between 10 milliseconds to 1 nanosecond.

27. The device of claim 26, wherein the switching occurs for each electrical pulse or within each electrical pulse.

28. The device of claim 27, wherein the electrical pulses together comprise a pulse protocol comprising a train of unipolar pulses followed by a train of unipolar pulses of opposite polarity or a train of bipolar pulses.

29. The device of claim 28, wherein the electrical pulses have a waveform which is square, triangular, trapezoidal, exponential decay, sawtooth, sinusoidal, or of alternating polarity, or comprise a combination of one or more waveform.