IRREVERSIBLE ELECTROPORATION (IRE) FOR CONGESTIVE OBSTRUCTIVE PULMONARY DISEASE (COPD)

Abstract

A method for treating Chronic Obstructive Pulmonary Disease (COPD) or chronic bronchitis to alleviate the discomforts of breathing by using non-thermal electroporation energy to ablate diseased portions of the lung including the bronchus, airways and alveoli which, in effect, opens the restrictive diseased portions thereby maximizing the overall surface area thereof causing improved airflow and uninhibited breathing.

Claims

1-20. (canceled)

21. A system comprising: an endobronchial device configured to be placed at a first treatment zone in a lung; a deployable monopolar electrode and a second electrode both configured to be operatively coupled to a generator; the deployable electrode configured to expand from a collapsed state to a deployed state at the first treatment zone; the generator configured to generate a first set of electrical pulses delivered through the deployed electrode to the first treatment zone and sufficient to non-thermally ablate tissue affected by bronchitis in the first treatment zone; the deployable electrode configured to be collapsed from the deployed state to the collapsed state and placed a second treatment zone in the lung; the deployable electrode configured to expand from the collapsed state to the deployed state at the second treatment zone; and the generator configured to generate a second set of electrical pulses delivered through the deployable electrode to the second treatment zone and sufficient to non-thermally ablate tissue affected by bronchitis in the second treatment zone.

22. The system of claim 21, wherein the tissue in both the first treatment zone and the second treatment zone is irreversibly electroporated.

23. The system of claim 21, wherein the second electrode is a monopolar electrode.

24. The system of claim 21, wherein the first treatment zone is a first area within the lung and the second treatment zone is a second area within the lung.

25. The system of claim 21, wherein the deployable electrode comprises an elongated flexible shaft.

26. The system of claim 21, further comprising an imaging unit.

27. The system of claim 21, wherein the tissue affected by bronchitis in both the first treatment zone and the second treatment zone comprise abnormal mucus-producing cells.

28. The system of claim 21, wherein both the first set of electrical pulses and the second set of electrical pulses are configured to induce cell necrosis without raising or lowering a temperature at both the first treatment zone and the second treatment zone.

29. The system of claim 21, wherein the generator is preprogrammed to deliver both the first set of electrical pulses and the second set of electrical pulses.

30. A system to non-thermally ablate tissue to treat a lung disease, comprising: an endoluminal device configured to be placed at a first treatment zone in a lung; a first electrode and a second electrode both configured to be operatively coupled to a generator; the first electrode configured to expand from a collapsed state to an expanded state at the first treatment zone; the generator configured to generate a first set of electrical pulses delivered between the first electrode and the second electrode such that tissue affected by bronchitis in the first treatment zone is non-thermally ablated; the first electrode configured to be collapsed from the expanded state to the collapsed state and placed a second treatment zone in the lung; the first electrode configured to expand from the collapsed state to the expanded state at the second treatment zone; and the generator configured to generate a second set of electrical pulses delivered between the first electrode and the second electrode such that tissue affected by bronchitis in the second treatment zone is non-thermally ablated.

31. The system of claim 30, wherein the tissue in both the first treatment zone and the second treatment zone is irreversibly electroporated.

32. The system of claim 31, wherein both the first set of electrical pulses and the second set of electrical pulses are configured induce cell necrosis without raising or lowering a temperature at both the first treatment zone and the second treatment zone.

33. The system of claim 32, wherein both the first set of electrical pulses and the second set of electrical pulses are configured to induce cell necrosis without raising or lowering a temperature at both the first treatment zone and the second treatment zone.

34. The system of claim 33, wherein the second electrode is to be placed inside the first treatment zone and the second treatment zone.

35. A system to non-thermally ablate lung tissue, comprising: an endoluminal device configured to be placed at a first treatment site in a lung; a first electrode and a second electrode both configured to be operatively coupled to a generator; the first electrode configured to transition from a collapsed state to an expanded state at the first treatment site; the generator is programed to generate a first set of electrical pulses delivered between the first electrode and the second electrode such that lung tissue in the first treatment site is non-thermally ablated; the first electrode configured to transition from the expanded state to the collapsed state and placed a second treatment site in the lung; the first electrode configured to transition from the collapsed state to the expanded state at the second treatment site; and the generator is programed to generate a second set of electrical pulses delivered between the first electrode and the second electrode such that lung tissue in the second treatment site is non-thermally ablated.

36. The system of claim 35, wherein the tissue in both the first treatment site and the second treatment site is irreversibly electroporated.

37. The system of claim 36, wherein both the first set of electrical pulses and the second set of electrical pulses are configured induce cell necrosis without raising or lowering a temperature at both the first treatment zone and the second treatment zone.

38. The system of claim 37, wherein the first electrode is a monopolar electrode.

39. The system of claim 38, wherein both the first set of electrical pulses and the second set of electrical pulses are bipolar pulses.

40. The system of claim 39, wherein the lung tissue in both the first treatment site and the second treatment site comprises abnormal mucus-producing cells.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 is a perspective view of a lowermost portion of the lung depicting an enlarged bronchus and alveoli.

[0024] FIG. 2A is an enlarged cross-sectional view of a normal bronchus.

[0025] FIG. 2B is an enlarged cross-sectional view of a bronchus affected by chronic bronchitis.

[0026] FIG. 3A is an enlarged cross-sectional view of normal alveoli.

[0027] FIG. 3B is an enlarged cross-sectional view of alveoli affected by emphysema.

[0028] FIG. 4 is a perspective view of the endotracheal procedure for performing IRE on a lung affected by chronic bronchitis showing a catheter passed through the trachea and positioned within the bronchus.

[0029] FIG. 5A is a perspective view of the endotracheal procedure for performing IRE on a lung affected by chronic bronchitis showing an IRE electrode balloon positioned within the bronchus.

[0030] FIG. 5B is an enlarged cross-sectional view of a deflated IRE electrode balloon positioned within the bronchus prior application of IRE energy.

[0031] FIG. 5C is an enlarged cross-sectional view of an inflated IRE electrode balloon positioned within the bronchus during the application of IRE energy.

[0032] FIG. 5D is an enlarged cross-sectional view of the bronchus post-treatment showing the restored diameter of the bronchus.

[0033] FIG. 6A is a perspective view of the percutaneous procedure of performing IRE detailing the use of an IRE probe to ablate the diseased region of the lung.

[0034] FIG. 6B is a perspective view of the percutaneous procedure of performing IRE detailing the use of two IRE probes to ablate the diseased region of the lung.

[0035] FIG. 7 is a flowchart showing the method of treating patients with COPD or chronic bronchitis using IRE ablation.

DETAILED DESCRIPTION OF THE INVENTION

[0036] FIG. 4 shows the endotracheal method of performing IRE on a lung (10) affected by chronic bronchitis. A catheter (24) is advanced through the trachea (26) to a diseased region (28) of the bronchus (12). Advancement through the trachea (26) is relatively simple and will optionally require a guidewire to select the advancement route through to the branching bronchus (12). Steering of the catheter (24) may be effected under real time imaging using video assisted thoracic surgery (VATS). Once the catheter (24) is in place inside the diseased region (28), a flexible IRE device (25) is inserted through the catheter (24) to the diseased region (28) of the bronchus (12). The flexible IRE device is used in the endotracheal method because it allows for the device to be easily steered through and properly positioned within the delicate intricacies of the lung (10) and into the bronchus (12). With the flexible IRE device (25) within the diseased region (28) of the lung (10), an IRE power source (not shown) is powered on and IRE energy is applied to ablate the inflamed bronchial tissue of the diseased region (28). To treat multiple bronchi, the IRE device (25) may then be retracted back into the catheter (24) and redeployed in an adjacent bronchus (12).

[0037] The endotracheal method of performing IRE can be executed endo-bronchially or exo-bronchially. FIG. 5A shows a more detailed view of the flexible IRE device (30) in place within the diseased region (28) of the lung (10) wherein the IRE device (30) includes an electrode balloon (36). Although an electrode balloon is shown, the endotracheal procedure is not limited to such, other devices may be employed. FIG. 5B details the electrode balloon (36), in a deflated state, in place within the decreased diameter airway (A2) of the inflamed inner bronchial wall (18) of the bronchus (12). The electrode balloon (36) includes a plurality of electrodes 37 positioned on the surface of the deflated balloon. Prior to application of IRE energy, the IRE power source (32) is powered on, the electrode balloon (36) is inflated as shown in FIG. 5C. The expansion of the balloon results in a partial increase in bronchial airway diameter. Electrodes 37 are shown in contact with the inner bronchial wall (18) of the bronchus. As IRE energy is then applied to the inner bronchial wall (18) of the bronchus, electrical current (39) flows from the electrodes (37) into the bronchial wall (18) tissue. The inflamed portion of the bronchus is ablated, reducing the thickness of the bronchus wall. After treatment, the diameter (D1) of bronchial airway (A1) increases as shown in FIG. 5D. The airflow is restored and breathing functions improve.

[0038] A percutaneous method of treating a lung affected by chronic bronchitis may also be used. Very much similar to the endotracheal method, the percutaneous method may be executed both endo-bronchially and exo-bronchially. The probe, with increased rigidity and strength relative to an IRE catheter probe, is inserted into the lung tissue through the skin using a direct stick approach. The distal end section of the probe is then advanced through a wall of the bronchus into the lumen. IRE energy is applied to ablate the tissue of the diseased region such that inflammation of the bronchus is decreased and breathing functions are enhanced.

[0039] FIGS. 6A and 6B show a method of performing IRE on an emphysemic lung (10) using a percutaneous approach. Although not shown, the endotracheal approach previously described may also be used. FIG. 6A details a bipolar IRE probe (50) inserted through the skin (46) to the target area of the lung (10) near the alveoli (14). Advancement and positioning of the probe (50) may be effected under real time imaging modalities such as ultrasound or CT. Once the probe (50) is in place in the targeted lung region, the IRE power source (32) is powered on and IRE energy is applied to the probe. Electrical current flows between distal electrode (56) and proximal electrode (54), creating a zone of ablation (52).

[0040] Alternatively, as shown in FIG. 6B, two IRE probes of opposite polarity may be used to ablate a desired lung tissue volume. Electrode probe (58), which may be of positive polarity, is positioned within the lung tissue a selected distance away from negative electrode probe (59). The application of electrical energy from power source (32) creates an electrical field between the two electrodes 61 and 62 as shown by ablation zone (52). In another embodiment (not shown), an electrode probe with deployable electrode tines may be used to apply IRE energy to lung tissue. In all these embodiments, the ablated tissue dies, thereby reducing the overall lung volume. For larger target areas, sequential ablations may be performed. As with LVRS, up to approximately 20-35% of the damaged lung may be non-surgically ablated. By reducing the lung volume, the remaining lung tissue and surrounding muscles are able to work more efficiently, improving air flow.

[0041] Ablation of the targeted region of diseased tissue is achieved with an IRE generator as the power source, utilizing a standard wall outlet of 110 volts (v) or 230 v with a manually adjustable power supply depending on voltage. The generator should have a voltage range of 100 v to 10,000 v and be capable of being adjusted at 100 v intervals. The applied ablation pulses are typically between 20 and 100 microseconds in length, and capable of being adjusted at 10 microsecond intervals. The preferred generator should also be programmable and capable of operating between 2 and 50 amps, with test ranges involving an even lower maximum where appropriate. It is further desired that the IRE generator includes 2 to 6 positive and negative connectors, though it is understood that the invention is not restricted to this number of connectors and may pertain to additional connector combinations and amounts understood in the art and necessary for optimal configurations for effective ablation. Preferably, IRE ablation involves 90 pulses with maximum field strengths of 400V/cm to 3000V/cm between electrodes. Pulses are applied in groups or pulse-trains where a group of 1 to 15 pulses are applied in succession followed by a gap of 0.5 to 10 seconds. Pulses can be delivered using probes, needles, and electrodes each of varying lengths suitable for use in not only with percutaneous and laparoscopic procedures, but with open surgical procedures as well. In endotracheal procedures, due to the delicate intricacies and general make-up of the lung, it is preferable that a flexible device be used to ensure proper placement and reduced risk of perforation, abrasion, or other trauma to the lung tissue.

[0042] Although preferred specifics of IRE ablation devices are set forth above, electro-medicine provides for ablation processes that can be performed with a wide range of variations. For instance, some ablation scenarios can involve 8 pulses with maximum field strengths between electrodes of 250V/cm to 500V/cm, while others require generators having a voltage range of 100 kV-300 kV operating with nano-second pulses with maximum field strengths of 2,000V/cm to, and in excess of, 20,000V/cm between electrodes. Electrodes can be made using a variety of materials, sizes, and shapes known in the art, and may be spaced at an array of distances from one another. Conventionally, electrodes have parallel tines and are square, oval, rectangular, circular or irregular shaped; having a distance of 0.5 to 10 centimeters (cm) between two electrodes; and a surface area of 0.1 to 5 cm.sup.2.

[0043] FIG. 7 is a flowchart detailing the basic method of performing IRE ablation on bronchitis or COPD patients. As detailed above, access to the diseased region is gained through open surgical, laparoscopical, percutaneous or endotracheal procedure. Once the IRE device is connected and in proper position, the IRE parameters are set. These parameters may vary and are selected depending upon several factors such as the diseased state, patient health and anatomy, and other considerations. After establishing and setting the required IRE energy parameters, the diseased region of the lung is ablated and the IRE device is removed. Thus, focal tissue ablation of the lung is achieved without causing harm to surrounding tissue and/or organs.

[0044] An unlimited number of variations and configurations for the present invention could be realized. The foregoing discussion describes merely exemplary embodiments illustrating the principles of the present invention, the scope of which is recited in the following claims. Those skilled in the art will readily recognize from the description, the claims, and drawings that numerous changes and modifications can be made without departing from the spirit and scope of the invention. Accordingly, the scope of the invention is not limited to the foregoing specification.