Tumor ablation instruments and techniques

Abstract

The boundaries of the tumor are determined.SOLUTION: A method for ablating a tumor (15) having a boundary in tissue of a subject includes advancing a distal region (200) of a tumor ablation device (102) into the tissue, wherein the distal region is fitted with electrodes (2, 4). The bioimpedance of the tissue is then sensed using the distal region of the instrument. In response to the sensed bioimpedance, the electrodes are positioned within the boundaries of the tumor. While the electrodes remain within the boundaries, electroporation pulses are applied to the tumor using the electrodes. Other embodiments are also described.SELECTED DRAWING: Figure 6C

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 191,992 to Taff, filed May 22, 2021, entitled "Adjustable electrode configurations for tumor ablation," which is incorporated herein by reference.

[0002] FIELD OF THE INVENTION This application relates to the field of medical devices, in particular devices for tumor ablation. [Background technology]

[0003] background High-intensity and short-duration electric field pulses can cause tissue ablation in a process called irreversible electroporation (IRE), which has been described in the art in connection with the treatment of tumors at various locations within the body, usually inserted percutaneously.

[0004] J. Ricke et al. (The ALICE Trial, Cardiovasc Intervent Radiol (2015) 38:401-408) described the use of IRE for the percutaneous treatment of lung tumors. The authors did not demonstrate the effectiveness of this technique and concluded that variations in the electrical properties between the tumor and surrounding tissue, along with inaccurate electrode positioning, caused inappropriate electric field distribution inside the target tissue. Summary of the Invention [Means for solving the problem]

[0005] Summary of the Invention The present disclosure relates to methods and systems for determining tumor boundaries using electrical impedance to position a treatment applicator within the tumor boundary. For example, the treatment applicator may include a treatment electrode, e.g., an electroporation electrode. It may be advantageous to position the treatment electrode within the tumor boundary to, for example, focus treatment on tumor tissue rather than surrounding tissue. It may be even more advantageous to position the treatment electrode near the tumor boundary to treat the entire tumor—e.g., to avoid leaving tumor cells near the tumor boundary untreated.

[0006] For some applications, it may be possible to determine tumor boundaries by sensing bioimpedance due to differences in tissue properties between the tumor itself and its surrounding tissue. For example, healthy lung tissue generally has high bioimpedance (e.g., due to the air-filled structure of the parenchyma and its alveoli), while lung tumors generally have substantially lower bioimpedance. Therefore, bioimpedance sensing electrodes positioned near and / or within a tumor may be able to provide information about the boundaries of tumors—particularly lung tumors. Furthermore, this difference in bioimpedance between a tumor and its surrounding tissue may enable successful electroporation of the tumor while minimizing collateral damage to the surrounding tissue. For example, the relatively high conductivity of a tumor compared to the surrounding tissue may facilitate conduction of the electroporation pulse throughout the tumor rather than into the surrounding tissue.

[0007] For some applications, a device having an electroporation electrode at a distal region of the device is advanced into the patient. In applications where the tumor is a lung tumor, the device may be advanced transbronchially into the patient, for example, through the patient's nose or mouth, down the trachea and into the patient's airways. For some applications, advancement is performed percutaneously (e.g., transluminally or transthoracically).

[0008] For some applications, the device includes one or more bioimpedance sensing electrodes in its distal region. Once the distal region is positioned at the tumor, the tumor's borders can be determined using the bioimpedance sensing electrodes. For some applications, due to differences in tissue properties between a tumor and its surrounding tissue, e.g., as described above, the device (e.g., its external control device) can determine (or facilitate the determination of) the tumor's borders by moving (or facilitating the movement of) the bioimpedance sensing electrodes relative to the tumor and sensing bioimpedance at different locations. For example, the bioimpedance sensing electrodes can be advanced into and / or out of the tumor so that the precise location of the transition (i.e., the border) between the inside and outside can be identified. Based on the identified border, a treatment applicator (e.g., an electroporation electrode) can be precisely positioned within the tumor (e.g., near the border) and used to deliver treatment, e.g., apply electroporation pulses to the tumor. For some applications, treatment is delivered while the bioimpedance sensing electrodes remain in place—e.g., at, just inside, or just outside the border. For some applications, therapy is administered after moving the bioimpedance sensing electrode. For some applications, the bioimpedance sensing electrode also functions as a therapy applicator, e.g., an electroporation electrode between which electroporation pulses are applied.

[0009] For some applications, the treatment applicator has a fixed and / or known position relative to the bioimpedance sensing electrodes so that once the tumor border is determined, the treatment applicator is positioned just inside the tumor border. For some applications, the treatment applicator is automatically positioned within the tumor by determining the tumor border using the bioimpedance sensing electrodes. For example, the device may be configured such that by positioning the bioimpedance sensing electrodes at or just outside the tumor border, the device can automatically position the corresponding electroporation electrodes just inside the border. For some applications, once the tumor border is determined, the surgeon can move the treatment applicator into and / or within the tumor using the known relative position between the treatment applicator and the bioimpedance sensing electrodes.

[0010] For some applications, bioimpedance sensing electrodes may be used to detect tumor boundaries and provide an alert, for example, indicating that no further advancement is required (or desired).

[0011] For some applications, the therapeutic applicator (e.g., electroporation electrode) is positioned axially between the bioimpedance sensing electrodes, and by identifying the bioimpedance sensing electrodes as being at (e.g., just outside) the tumor boundary, automatically verifying that the electroporation electrode is just inside the boundary.

[0012] For some applications, bioimpedance sensing electrodes may be used to determine whether a lesion or growth is a cancerous tumor—e.g., to facilitate diagnosis. For example, the bioimpedance of a cancerous tumor may differ from the bioimpedance of a non-cancerous lesion or growth.

[0013] For some applications, by monitoring the bioimpedance measured by one or more bioimpedance sensing electrodes over a patient's respiratory cycle, it may be possible to determine whether one or more bioimpedance sensing electrodes (and therefore one or more electroporation electrodes) are positioned within a tumor. For example, the bioimpedance value of lung parenchyma may change (e.g., oscillate) during the respiratory cycle (e.g., impedance decreases during exhalation and increases during inhalation), whereas a tumor may have a more consistent bioimpedance value throughout the respiratory cycle. For some applications, receiving a signal with an oscillation magnitude above a threshold magnitude indicates that the tissue in which the bioimpedance sensing electrode is located is lung tissue (e.g., lung parenchyma) rather than tumor tissue.

[0014] For some applications, the frequency of vibrations sensed in the tumor by the bioimpedance sensing electrodes is compared to the frequency of the patient's respiratory cycle to ensure that the sensed vibrations reflect the respiratory cycle and do not arise from other factors (e.g., the patient's pulse). This may therefore provide the surgeon with further confirmation as to whether a particular tissue is a tumor and / or the location of one or more bioimpedance sensing electrodes relative to the tumor.

[0015] Therefore, according to some applications, a method is provided that includes (i) receiving information indicative of the bioimpedance of tissue in a subject's lung (optionally, information indicative of oscillations in the bioimpedance, e.g., the magnitude and / or frequency of the oscillations), and (ii) in response, determining (e.g., diagnosing) whether the tissue is tumorous and / or cancerous.

[0016] Generally, some embodiments of the present disclosure include a device made up of at least two electrodes that are movable relative to one another.

[0017] In some embodiments, the electrodes may be electrically and / or mechanically connected to an external ground pad to function as a single monopolar electrode, which may comprise one or more bioimpedance sensing electrodes.

[0018] In some embodiments, one or more electrodes (i.e., inner electrodes) are configured to pass through a second electrode (outer electrode). In some embodiments, the electrodes are connected to an energy source configured to apply the high voltage necessary to induce electroporation (reversible and irreversible).

[0019] In some embodiments, the device is configured to be delivered via a bronchoscopic procedure to treat tumors located in the lungs or airways.

[0020] In some embodiments, the electrodes are curved or flexible.

[0021] In some embodiments, the device may also include a sensor attached near or to one or more of the electrodes to allow for precise positioning inside the tumor.

[0022] In some embodiments, the sensor is in the form of an electrode and measures an impedance value between the sensor and the treatment electrode.

[0023] In some embodiments, following introduction of the outer electrode into the tumor, an inner electrode is also inserted through the outer electrode into the tumor. A voltage is then applied between the inner and outer electrodes. The voltage induces electroporation (either reversible or irreversible) in the vicinity of the electrodes. The electrodes can then be adjusted to cover additional segments of the tumor. In some embodiments, the inner electrode may be inserted into the tumor before inserting the outer electrode, and the outer electrode may be inserted into the tumor over the inner electrode.

[0024] In some embodiments, a sensor mounted proximally to the outer electrode is used to verify that the outer electrode has entered the tumor.

[0025] In some embodiments, a sensor mounted distal to the inner electrode is used to verify that the inner electrode has reached the distal margin of the tumor.

[0026] In some embodiments, coverage of additional segments of the tumor is achieved by moving the inner electrode.

[0027] In some embodiments, coverage of additional segments of the tumor is achieved using curved or deflectable electrodes.

[0028] Therefore, according to some applications, an apparatus for ablating a tumor is provided, the apparatus including a device having a distal region.

[0029] For some applications, the device includes a bioimpedance sensing electrode at the distal region and a treatment applicator adapted to ablate tumor tissue and to be positionally fixed at the distal region relative to the bioimpedance sensing electrode.

[0030] For some applications, the device includes a shaft to which bioimpedance sensing electrodes are attached, the shaft comprising: to a first location where a bioimpedance sensing electrode is placed within the tumor; and to a second location where the bioimpedance sensing electrodes are placed outside the tumor and the treatment applicator is placed within the tumor. It is possible to move forward.

[0031] For some applications, in a first position of the shaft, the treatment applicator is positioned outside the tumor.

[0032] For some applications, the distal region defines a tissue piercing tip.

[0033] For some applications, the distal region can be curved within the tumor.

[0034] For some applications, the device is a first device, and the apparatus further includes at least one additional device, each additional device having a distal region including a therapeutic applicator and a bioimpedance sensing electrode.

[0035] For some applications, a therapeutic applicator is attached to the shaft proximally from the bioimpedance sensing electrodes.

[0036] For some applications, a therapeutic applicator is attached to the shaft distal to the bioimpedance sensing electrodes.

[0037] For some applications, the shaft is flexible.

[0038] For some applications, the shaft is rigid.

[0039] For some applications: the therapeutic applicator includes an electroporation electrode; the shaft is a first shaft, and the electroporation electrode is disposed on the first shaft; The instrument further includes a second shaft; and The first shaft and the second shaft are reversibly movable relative to one another by the first shaft being axially slidable relative to the second shaft.

[0040] For some applications: the first shaft is an inner shaft; the second shaft is an outer shaft that is slidable over the inner shaft; and The device is configured so that the effective length of the electroporation electrode is adjustable by sliding the outer shaft over the electroporation electrode.

[0041] For some applications, a bioimpedance sensing electrode is positioned on the first shaft, distal from the electroporation electrode.

[0042] For some applications, the device further includes another bioimpedance sensing electrode disposed on the second shaft.

[0043] For some applications: the tumor is located in the subject's lung; and The device is configured to determine the boundaries of lung tumors by sensing performed by bioimpedance sensing electrodes.

[0044] For some applications, the device includes a bronchoscope and is transbronchially advanceable to the lungs, and the shaft is deliverable via the bronchoscope to the tumor.

[0045] For some applications, the device further includes a remote electrode, and the device is configured to sense bioimpedance between the remote electrode and the bioimpedance sensing electrode.

[0046] For some applications, the remote electrode is a skin electrode.

[0047] For some applications, the treatment applicator: an electroporation electrode; and The electrodes are adapted to apply electroporation pulses to the tumor.

[0048] For some applications, the device further includes a remote electrode, and the device is configured to apply an electroporation pulse between the remote electrode and the electroporation electrode.

[0049] For some applications, the device is configured to sense bioimpedance at the tumor by sensing bioimpedance between the electroporation electrode and the bioimpedance sensing electrode.

[0050] For some applications: the electroporation electrode is the first electrode; the therapeutic applicator further includes a second electroporation electrode; and The device is configured to apply an electroporation pulse between the first electrode and the second electrode.

[0051] For some applications, the first and second electroporation electrodes are attached to a distal region, which is reversibly lengthenable to vary the axial distance between the first and second electrodes.

[0052] For some applications, the distal region: a distal portion having a first electroporation electrode disposed thereon; and A proximal portion where the second electroporation electrode is located. a telescoping assembly having The distal region is reversibly lengthenable by axially sliding the distal and proximal portions relative to one another.

[0053] For some applications, the bioimpedance sensing electrode is positioned in the distal portion, distal to the first electroporation electrode.

[0054] For some applications, the device further includes a second bioimpedance sensing electrode positioned in the proximal portion, proximal from the second electroporation electrode.

[0055] For some applications: the shaft is a first shaft, and the first electroporation electrode is disposed on the first shaft; the device further includes a second shaft, the second electroporation electrode being disposed on the second shaft; and The first shaft and the second shaft are reversibly movable relative to one another by the first shaft being slidable through the second shaft.

[0056] For some applications, the first shaft and the second shaft diverge relative to one another at the distal region.

[0057] For some applications, each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

[0058] For some applications, the second shaft defines a side port through which the first shaft is advanceable.

[0059] For some applications, the first shaft is bendable relative to the second shaft.

[0060] For some applications, the first shaft is advanceable from the distal end of the second shaft.

[0061] For some applications, the device includes a controller adapted to receive signals from the bio-impedance sensing electrodes and, in response, to provide an output indicative of the bio-impedance of tissue adjacent to the bio-impedance sensing electrodes.

[0062] For some applications, the controller is adapted to determine a change in the signal over at least a portion of the patient's respiratory cycle, and the output is indicative of a change in bioimpedance of tissue adjacent the bioimpedance sensing electrode over at least a portion of the respiratory cycle.

[0063] For some applications, the controller is configured to output information indicative of the position of the bioimpedance sensing electrodes relative to the tumor in response to the signal.

[0064] For some applications: The device includes a terminal electrically connected to the bioimpedance sensing electrode via a conductor extending along the shaft; and The control unit is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control unit to the terminals.

[0065] For some applications: The therapeutic applicator is configured to apply electroporation pulses to the tumor; and The controller includes a generator electrically connectable to the treatment applicator and adapted to drive the treatment applicator to apply electroporation pulses.

[0066] For some applications, the treatment applicator is fixed in position relative to the bioimpedance sensing electrodes at a distance of 10 mm or less.

[0067] For some applications, the treatment applicator is positionally fixed relative to the bioimpedance sensing electrodes at a distance of 5 mm or less.

[0068] Additionally, in accordance with some applications, an apparatus is provided for ablating tumors in the lungs of a subject.

[0069] For some applications, the device: shaft; a bioimpedance sensing electrode attached to a distal region of the shaft; and an electroporation electrode attached to the distal region of the shaft at a fixed distance from the bioimpedance sensing electrode; This includes equipment including:

[0070] For some applications, the distal region of the shaft is advanceable to a location within the lung where: An electroporation electrode is placed within the borders of the tumor; and Bioimpedance sensing electrodes are placed outside the boundaries of the tumor.

[0071] For some applications, the device is configured to determine the boundaries of lung tumors by sensing performed by bioimpedance sensing electrodes.

[0072] For some applications, the device includes a bronchoscope and is transbronchially advanceable to the lungs, and the shaft is deliverable via the bronchoscope to the tumor.

[0073] For some applications, the distal region defines a tissue piercing tip.

[0074] For some applications, the distal region can be curved within the tumor.

[0075] For some applications, the electroporation electrode is attached to the shaft proximally from the bioimpedance sensing electrode.

[0076] For some applications, the electroporation electrode is attached to the shaft distal to the bioimpedance sensing electrode.

[0077] For some applications, the shaft is flexible.

[0078] For some applications, the shaft is rigid.

[0079] For some applications, the device further includes a remote electrode, and the device is configured to sense bioimpedance between the remote electrode and the bioimpedance sensing electrode.

[0080] For some applications, the remote electrode is a skin electrode.

[0081] For some applications, the electroporation electrode is adapted to apply an electroporation pulse to the tumor.

[0082] For some applications, the device further includes a remote electrode, and the device is configured to apply an electroporation pulse between the electroporation electrode and the remote electrode.

[0083] For some applications, the device is configured to sense bioimpedance at the tumor by sensing bioimpedance between the electroporation electrode and the bioimpedance sensing electrode.

[0084] For some applications: the electroporation electrode is a first electroporation electrode; the device further comprises a second electroporation electrode; and The device is configured to apply an electroporation pulse between the first electroporation electrode and the second electroporation electrode.

[0085] For some applications: the shaft is a first shaft, and the first electroporation electrode is disposed on the first shaft; the device further includes a second shaft, the second electroporation electrode being disposed on the second shaft; and The first shaft and the second shaft are reversibly movable relative to one another by the first shaft being slidable through the second shaft.

[0086] For some applications, the first shaft and the second shaft diverge relative to one another at a distal region of the instrument.

[0087] For some applications, each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

[0088] For some applications, a bioimpedance sensing electrode is positioned on the first shaft distal to the first electroporation electrode.

[0089] For some applications, the device further includes a second bioimpedance sensing electrode disposed on the second shaft proximally from the second electroporation electrode.

[0090] For some applications, the second shaft defines a side port through which the first shaft is advanceable.

[0091] For some applications, the first shaft is bendable relative to the second shaft.

[0092] For some applications, the first shaft is advanceable from the distal end of the second shaft.

[0093] For some applications, the device includes a controller adapted to receive signals from the bio-impedance sensing electrodes and, in response, to provide an output indicative of the bio-impedance of tissue adjacent to the bio-impedance sensing electrodes.

[0094] For some applications, the controller is adapted to determine a change in the signal over at least a portion of the patient's respiratory cycle, and the output is indicative of a change in bioimpedance of tissue adjacent the bioimpedance sensing electrode over at least a portion of the respiratory cycle.

[0095] For some applications, the controller is configured to provide an output in response to the signal that is indicative of the position of the bioimpedance sensing electrode relative to the tumor.

[0096] For some applications: The device includes a terminal electrically connected to the bioimpedance sensing electrode via a conductor extending along the shaft; and The control unit is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control unit to the terminals.

[0097] For some applications, the controller is adapted to provide a current to generate the signal.

[0098] For some applications: the electroporation electrode is configured to apply an electroporation pulse to the tumor; and The controller includes a generator electrically connectable to the electroporation electrodes and adapted to drive the electroporation electrodes to apply electroporation pulses.

[0099] For some applications, the fixed distance is 10 mm or less.

[0100] For some applications, the fixed distance is 5 mm or less.

[0101] For some applications, the shaft is a first shaft, and the device further includes at least a second shaft, the second shaft having a distal region including an electroporation electrode and a bioimpedance sensing electrode.

[0102] For some applications: the instrument is a first instrument, the first shaft is a shaft of the first instrument, and The apparatus further includes a second instrument, and the second shaft is the shaft of the second instrument.

[0103] Further, according to some applications, there is provided a method for ablating a tumor in tissue of a subject, the tumor having a boundary, the method comprising: advancing a distal region of a tumor-ablating device into the tissue, the distal region having an electrode attached thereto; Sensing tissue bioimpedance using a distal region of the device Includes:

[0104] For some applications, electrodes are positioned within the boundaries of the tumor in response to sensed bioimpedance.

[0105] For some applications, electroporation pulses are applied to the tumor using electrodes while the electrodes remain within the boundaries.

[0106] For some applications: Sensing the bioimpedance of the tissue includes sensing a change in the bioimpedance of the tissue over at least a portion of a respiratory cycle of the subject; and Positioning electrodes within the boundaries of the tumor in response to sensed changes in bioimpedance. Includes:

[0107] For some applications: an electrode is positioned on the first shaft of the instrument; The instrument further includes a second shaft; and The method further includes axially sliding the first shaft relative to the second shaft subsequent to positioning the electrode within the boundary of the tumor.

[0108] For some applications: the first shaft is an inner shaft; the second shaft is an outer shaft that is slidable over the inner shaft; and Axially sliding the first shaft relative to the second shaft includes axially sliding the outer shaft over the inner shaft to adjust the effective length of the electrode.

[0109] For some applications: the electrode is an electroporation electrode; the distal region further includes a bioimpedance sensing electrode; Sensing bioimpedance using a distal region of the device includes sensing bioimpedance using a bioimpedance sensing electrode; and Positioning the electroporation electrode within the boundaries of the tumor involves moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor.

[0110] For some applications: Sensing bioimpedance using the bioimpedance sensing electrode includes sensing bioimpedance using the bioimpedance sensing electrode while the bioimpedance sensing electrode is electrically connected to a controller, the controller being configured to provide an alert in response to a change in bioimpedance detected by the bioimpedance sensing electrode upon exit of the bioimpedance sensing electrode from the tumor; and Positioning the electrode within the boundary of the tumor includes positioning the electrode within the boundary in response to an alert.

[0111] For some applications, the bioimpedance sensing electrode is positioned distal to the electroporation electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor includes moving the distal region of the device distally through the tumor until the bioimpedance sensing electrode exits the distal boundary of the tumor.

[0112] For some applications, the bioimpedance sensing electrode is positioned proximally relative to the electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor includes moving the distal region of the device proximally through the tumor until the bioimpedance sensing electrode exits the proximal boundary of the tumor.

[0113] For some applications: the electrode is a first electrode attached to a first portion of the distal region; the distal region further includes a second electrode attached to a second portion of the distal region; the first portion and the second portion are operable such that the first electrode is movable relative to the second electrode; and Applying an electroporation pulse to the tumor using the electrodes includes applying the electroporation pulse between a first electrode and a second electrode.

[0114] For some applications: the first portion is a distal portion of the first shaft; the second portion is a distal portion of the second shaft; and Positioning the electrode within the boundary of the tumor includes sliding the first shaft through the second shaft to position the electrode within the boundary of the tumor.

[0115] For some applications, sensing the bioimpedance of tissue includes sensing the bioimpedance of tissue between the first portion and the second portion.

[0116] For some applications, the method includes applying an electroporation pulse followed by: repositioning the electrode within the tumor; and Applying another electroporation pulse to the tumor using electrodes Includes:

[0117] For some applications, the method further includes sensing the bioimpedance of the tissue using a distal region of the device following repositioning the electrode within the tumor and prior to applying another electroporation pulse.

[0118] Further, according to some applications, there is provided an apparatus for use on a tumor, the apparatus including a tumor ablation instrument having a distal region including a first portion, the first portion comprising: a first bioimpedance sensing electrode; a first electroporation electrode mounted in position relative to the first bioimpedance sensing electrode; Includes:

[0119] For some applications, the distal region further includes a second portion, the second portion comprising: a second bioimpedance sensing electrode; and a second electroporation electrode mounted in position relative to the second bioimpedance sensing electrode; Includes:

[0120] For some applications, the distal region is operable to vary the axial distance between the first and second portions.

[0121] For some applications, the first portion is a first portion of a distal region of a first shaft of the instrument, and the second portion is a second portion of a distal region of a second shaft of the instrument.

[0122] For some applications, the first shaft and the second shaft diverge relative to one another at the distal region.

[0123] For some applications, each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

[0124] For some applications, the distal region is operable to vary the axial distance between the first and second portions by allowing the first shaft to slide within the second shaft.

[0125] For some applications, the first shaft is advanceable from the distal end of the second shaft.

[0126] For some applications, a first bioimpedance sensing electrode is positioned on the first shaft distal to the first electroporation electrode.

[0127] For some applications, a second bioimpedance sensing electrode is positioned on the second shaft proximally from the second electroporation electrode.

[0128] For some applications, a first bioimpedance sensing electrode is positioned on the first shaft proximally from the first electroporation electrode.

[0129] For some applications, the second shaft defines a side port through which the first shaft is advanceable.

[0130] For some applications, the first shaft is bendable relative to the second shaft.

[0131] Additionally, according to some applications, there is provided an apparatus for ablating a tumor in a lung of a subject, the apparatus comprising: shaft; a bioimpedance sensing electrode attached to a distal region of the shaft; and an electroporation electrode attached to the distal region of the shaft at a known distance from the bioimpedance sensing electrode; This includes equipment including:

[0132] For some applications, the distal region of the shaft can be advanced to a location within the lung where: An electroporation electrode is placed within the borders of the tumor; and Bioimpedance sensing electrodes are placed outside the boundaries of the tumor.

[0133] Additionally, in accordance with some applications, there is provided an apparatus for ablating a tumor, the apparatus comprising: shaft; a first bioimpedance sensing electrode disposed in a distal region of the shaft; a second bioimpedance sensing electrode disposed in a distal region of the shaft; and an electroporation electrode axially disposed on the shaft between the first bioimpedance sensing electrode and the second bioimpedance sensing electrode; This includes equipment including:

[0134] Further, according to some applications, there is provided a method for ablating a tumor, the method comprising: advancing a distal region of a tumor ablation device into the tumor, the distal region having an electroporation electrode attached thereto and flanked by a proximal bioimpedance sensing electrode and a distal bioimpedance sensing electrode; Includes:

[0135] For some applications, the method further includes determining a distal boundary of the tumor by sensing bioimpedance, facilitated by a distal bioimpedance sensing electrode.

[0136] For some applications, the method further includes, in response to determining the distal boundary, and while the electroporation electrode is positioned within the distal boundary, driving the electroporation electrode to apply a first electroporation pulse to the tumor.

[0137] For some applications, the method further includes determining the proximal boundary of the tumor by sensing bioimpedance, facilitated by a proximal bioimpedance sensing electrode.

[0138] For some applications, the method further includes, in response to determining the proximal boundary, and while the electroporation electrode is positioned within the proximal boundary, driving the electroporation electrode to apply a second electroporation pulse to the tumor.

[0139] For some applications, driving the electroporation electrode to apply a first electroporation pulse to the tumor includes driving the electroporation electrode to apply the first electroporation pulse to the tumor before applying a second electroporation pulse to the tumor.

[0140] For some applications, driving the electroporation electrode to apply a first electroporation pulse to the tumor includes driving the electroporation electrode to apply the first electroporation pulse to the tumor followed by applying a second electroporation pulse to the tumor.

[0141] For some applications, the method further includes applying a plurality of electroporation pulses to the tumor as the distal region of the device is advanced through the tumor.

[0142] Further, according to some applications, a method is provided for use with a lung of a subject, the method including receiving information indicative of oscillations of bioimpedance of tissue within the lung.

[0143] For some applications, the method further includes, in response, determining whether the tissue is tumor tissue.

[0144] For some applications, determining whether tissue is tumor tissue includes: determining whether the magnitude of the vibration is below a threshold magnitude; and In response to determining that the size is below a threshold, determining that the tissue is tumor tissue.

[0145] For some applications, determining whether tissue is tumor tissue includes: determining whether the magnitude of the vibration exceeds a threshold magnitude; and In response to determining that the size is above a threshold, determining that the tissue is not tumor tissue.

[0146] For some applications, determining whether the tissue is tumor tissue further includes determining whether the frequency of the vibrations matches the frequency of vibrations of a portion of a respiratory cycle.

[0147] Further, according to some applications, a method is provided for use with a lung of a subject, the method including receiving information indicative of the bioimpedance of tissue within the lung.

[0148] For some applications, the method further includes, in response, determining whether the tissue is cancerous.

[0149] Further, according to some applications, there is provided an apparatus for use on a tumor, the apparatus including a tumor ablation device having a distal region, the device comprising: an inner shaft fitted with an electroporation electrode; and an outer shaft that is axially slidable over the inner shaft to facilitate adjustment of the effective length of the electroporation electrode; Includes: The adjustment is such that distal advancement of the outer shaft over the inner shaft progressively covers the electroporation electrode, thereby progressively shortening the effective length of the electroporation electrode; and Proximal extension of the outer shaft over the inner shaft progressively exposes the electroporation electrode, thereby progressively increasing the effective length of the electroporation electrode.

[0150] For some applications, the outer shaft is formed from an electrical insulator.

[0151] For some applications: the electroporation electrode is configured to apply an electroporation pulse to the tumor; and The device further includes a controller including a generator electrically connectable to the electroporation electrodes and adapted to drive the therapeutic applicator to apply electroporation pulses.

[0152] For some applications, the device includes a bioimpedance sensing electrode attached to the distal region.

[0153] For some applications: the bioimpedance sensing electrode is a first bioimpedance sensing electrode; a first bioimpedance sensing electrode attached to the inner shaft distal to the electroporation electrode; and A second bioimpedance sensing electrode is attached to the outer shaft.

[0154] For some applications, the device includes a controller adapted to receive signals from the bio-impedance sensing electrodes and, in response, to provide an output indicative of the bio-impedance of tissue adjacent to the bio-impedance sensing electrodes.

[0155] For some applications, the controller is adapted to determine a change in the signal over at least a portion of the patient's respiratory cycle, and the output is indicative of a change in bioimpedance of tissue adjacent the bioimpedance sensing electrode over at least a portion of the respiratory cycle.

[0156] For some applications, the controller is configured to output information indicative of the position of the bioimpedance sensing electrodes relative to the tumor in response to the signal.

[0157] For some applications: The device includes a terminal electrically connected to the bioimpedance sensing electrode by a conductor extending along the shaft; and The control unit is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control unit to the terminals.

[0158] Further, according to some applications, there is provided a method for ablating a tumor, the method comprising: advancing a distal region of a tumor ablation device into a tumor, the device comprising: an inner shaft equipped with an electroporation electrode; and an outer shaft adapted to slide over the inner shaft Including Includes:

[0159] For some applications, the method further includes positioning a distal end of the electroporation electrode within the tumor.

[0160] For some applications, the method further includes adjusting the effective length of the electroporation electrode by sliding the outer shaft over the inner shaft.

[0161] For some applications, the method further includes activating an electroporation electrode to apply an electroporation pulse to the tumor.

[0162] For some applications, adjusting the effective length of the electroporation electrode by sliding the outer shaft over the inner shaft includes adjusting the effective length of the electroporation electrode until the electroporation electrode spans a desired length of the tumor.

[0163] For some applications, adjusting the effective length of the electroporation electrode until the electroporation electrode spans a desired length of the tumor includes adjusting the effective length of the electroporation electrode until the electroporation electrode spans the entire length of the tumor.

[0164] For some applications: The distal region further includes a bioimpedance sensing electrode; and Adjusting the effective length of the electroporation electrode includes adjusting the effective length guided by sensing performed by the bioimpedance sensing electrode.

[0165] For some applications, adjusting the effective length, guided by sensing performed by the bioimpedance sensing electrodes, involves moving a distal region of the device through the tumor until the bioimpedance sensing electrodes exit the tumor.

[0166] For some applications, adjusting the effective length guided by sensing performed by the bioimpedance sensing electrodes includes adjusting the effective length guided by sensing performed by the bioimpedance sensing electrodes while the bioimpedance sensing electrodes are electrically connected to a controller, the controller being configured to provide an alert in response to a change in bioimpedance detected by the bioimpedance sensing electrodes upon exit of the bioimpedance sensing electrodes from the tumor.

[0167] For some applications, a bioimpedance sensing electrode is positioned on the inner shaft distal to the electroporation electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor includes moving the inner shaft distally through the tumor until the bioimpedance sensing electrode exits the distal boundary of the tumor.

[0168] For some applications: the bioimpedance sensing electrode is a first bioimpedance sensing electrode; and The distal region further includes a second bioimpedance sensing electrode disposed on the outer shaft; and Moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor includes moving the outer shaft proximally through the tumor until the second bioimpedance sensing electrode exits the proximal boundary of the tumor.

[0169] The present invention will be more fully understood from the following detailed description of its application in conjunction with the drawings. [Brief explanation of the drawings]

[0170] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] 1 is a schematic illustration of an apparatus for electroporation ablation, according to some embodiments of the present disclosure. [Figure 2] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 3] 1 is a schematic illustration of an apparatus for electroporation ablation, according to some embodiments of the present disclosure. [Figure 4] 1 is a cross-sectional view of a shaft according to some embodiments of the present disclosure. [Figure 5] 1 is a schematic illustration of an apparatus for electroporation ablation, according to some embodiments of the present disclosure. [Figure 6A] 1A-1C are schematic diagrams of steps in a technique for ablating tumors guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 6B] 1A-1C are schematic diagrams of steps in a technique for ablating tumors guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 6C] 1A-1C are schematic diagrams of steps in a technique for ablating tumors guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 6D] 1A-1C are schematic diagrams of steps in a technique for ablating tumors guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 7] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation including multiple distal regions, according to some embodiments of the present disclosure. [Figure 8]FIG. 1 is a schematic diagram of an apparatus for electroporation ablation including multiple distal regions, according to some embodiments of the present disclosure. [Figure 9A] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation including multiple distal regions, according to some embodiments of the present disclosure. [Figure 9B] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation including multiple distal regions, according to some embodiments of the present disclosure. [Figure 10] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 11A] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 11B] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 11C] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 12] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 13A] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 13B] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. [Figure 13C] FIG. 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing, according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0171] Detailed Description Methods and systems are provided for determining tumor boundaries using electrical impedance to position a treatment applicator within the tumor boundary. For example, the treatment applicator may include a treatment electrode, e.g., an electroporation electrode. It may be advantageous to position the treatment electrode within the tumor boundary to, for example, focus treatment on tumor tissue rather than surrounding tissue. It may be even more advantageous to position the treatment electrode near the tumor boundary to treat the entire tumor—e.g., to avoid leaving tumor cells near the tumor boundary untreated.

[0172] For some applications, it may be possible to determine tumor boundaries by sensing bioimpedance due to differences in tissue properties between the tumor itself and its surrounding tissue. For example, while healthy lung tissue generally has a high bioimpedance (e.g., due to the air-filled structure of the parenchyma and its alveoli), lung tumors generally have a substantially lower bioimpedance. Therefore, bioimpedance sensing electrodes positioned near and / or within a tumor may be able to provide information about the boundaries of tumors—particularly lung tumors. Furthermore, this difference in bioimpedance between a tumor and its surrounding tissue may enable successful electroporation of the tumor while minimizing collateral damage to the surrounding tissue. For example, the relatively high conductivity of a tumor compared to surrounding tissue may facilitate conduction of the electroporation pulse throughout the tumor rather than into the surrounding tissue.

[0173] Reference is now made to Figure 1, which is a schematic illustration of a system 1000 for electroporative ablation of tumors, according to several applications. System 1000 includes an apparatus (e.g., device) 101 and may further include a controller 1010. Controller 1010 may include a generator (or power source) 7.

[0174] As shown in FIG. 1 , the device 101 may include at least one shaft (e.g., a tube, catheter, rod, and / or bronchoscope), e.g., shaft 1, and have a distal region 100. At least a portion of the distal region 100 is adapted to be advanced into a tumor. For some applications, the distal region 100 may enter a body lumen and be guided therethrough to access the tumor. For some applications, as shown in FIGS. 6A-D , the device 101 is advanced into a patient's body, e.g., into the patient's lung 50. For applications in which the tumor is a lung tumor, the device may be advanced into the patient's body transbronchially (e.g., via a bronchoscope)—e.g., through the patient's nose or mouth, down the patient's trachea, and into the airways (e.g., bronchi). For some such applications, the distal region 100 may then enter the airways (e.g., using the tissue piercing tip 16 of the distal region) and enter the parenchyma adjacent to the tumor. For some such applications, the shaft 1 may be flexible. For some applications, advancement is percutaneous (e.g., transluminally or transthoracically). For some such applications, shaft 1 may be rigid.

[0175] A first electroporation electrode 4 is positioned in the distal region 100 (e.g., the electrode may be attached to the shaft of the device), and advancing the distal region into the tumor also advances the electrode 4 into the tumor. For some embodiments, a second electroporation electrode 2 may also be positioned in the distal region 100—e.g., also positioned within the tumor so that an electroporation pulse may be applied between the first and second electrodes to electroporate the tumor. For some applications, electrodes 2 and 4 may be considered to be (e.g., may jointly define) components of a therapeutic applicator of device 101.

[0176] The distal region 100 is reversibly lengthenable to vary the axial distance L between the electrodes 2 and 4. For some applications, the distal region 100 may include a telescoping assembly—e.g., having a distal portion 14 and a proximal portion 12 that are axially slidable relative to one another. For some such applications, the shaft 1 is an outer shaft through which the inner shaft 3 of the instrument 101 is axially slidable. For some such applications, the first electrode 4 is disposed at the distal portion 14 of the distal region, and the second electrode 2 is disposed at the proximal portion 12 of the distal region. The distal portion 14 may be defined by a distal portion of the shaft 3. The proximal portion 12 may be defined by a distal portion of the shaft 1.

[0177] For some such applications, shafts 1 and 3 are coaxial. As explained above, to successfully electroporate the entire tumor, it may be advantageous to position electrodes 2 and 4 within the tumor near (e.g., at) their respective (e.g., opposing) borders. For such applications, such positioning of electrodes 2 and 4 within the tumor may be facilitated by lengthening and / or shortening (e.g., telescoping) them to adjust the distance L between the electrodes.

[0178] The controller 1010 (e.g., its generator 7) is adapted to drive electrodes 2 and 4 to apply electroporation pulses therebetween. In the proximal region 150 of the device 101, the device may include terminals 5 and 6, through which electrodes 2 and 4, respectively, may be electrically connected to the controller 1010 (e.g., generator 7). For example, wires extending from the controller may be connected to the terminals—e.g., prior to use. Electrodes 2 and 4 may be electrically connected to terminals 5 and 6, respectively, via conductors (e.g., wires) extending along the corresponding shaft(s). For example, one conductor may extend from electrode 4 along shaft 3 (e.g., via its lumen and / or within its sidewall) to proximal terminal 6, and / or another conductor may extend from electrode 2 along shaft 1 (e.g., via its lumen and / or within its sidewall) to proximal terminal 5. The wires may be electrically insulated from each other.

[0179] Reference will now be made to Figures 2 and 6A-D, which are schematic illustrations of a system 2000 for electroporative ablation of tumors 15, according to some applications. System 2000 includes an instrument (e.g., device) 102 and may further include a controller 2010. Controller 2010 may include a generator (or power source) 7a. Like instrument 101, instrument 102 may include at least one shaft 1 (e.g., a flexible tube, catheter, rod, and / or bronchoscope) and have a distal region 200 adapted to be advanced into tumor 15. Also like instrument 101, first and second electroporation electrodes 4 and 2 are positioned at distal region 200 to apply electroporation pulses and ablate the tumor. For some applications, distal region 200 may be reversibly lengthened to change the axial distance between electrodes 2 and 4, for example, by distal region 200 including a telescoping assembly (e.g., by a telescoping arrangement of shafts 1 and 3), or by any other means. For some applications, system 2000 may be considered a variation of system 1000, e.g., device 102 may be considered a variation of device 101.

[0180] Device 102 is similar to device 101 described above, but may also include one or more bioimpedance sensing electrodes at its distal region 200, such as a first electroporation electrode and a second bioimpedance sensing electrode 9. For some applications, these bioimpedance sensing electrodes may be separate electrodes distinct from electroporation electrodes 2 and 4 and may be electrically connected to controller 2010 independently of the electroporation electrodes.

[0181] Although each of the bioimpedance sensing electrodes described herein has been described and referred to as a single electrode, any of these bioimpedance sensing electrodes may in fact represent a set of electrodes that may work together—for example, to function as a bioimpedance sensor (e.g., further working together with the controller 2010). That is, for some applications, any of the bioimpedance sensing electrodes described herein may be comprised of two or more (e.g., multiple) electrodes. For some such applications, such a bioimpedance sensing electrode (including multiple individual electrodes) may be considered to be a bioimpedance sensor, either alone or in combination with the controller 2010.

[0182] As well as being adapted to drive electrodes 2 and 4 to apply electroporation pulses therebetween (e.g., via generator 7a), controller 2010 may be adapted to receive signals from bioimpedance sensing electrodes 8 and 9 to determine the position of electrodes 2 and 4 relative to the tumor, as described below. At proximal region 250 of device 102, the device may include terminals 5 and 6, via which electrodes 2 and 4, respectively, may be electrically connected to controller 2010 (e.g., generator 7)—e.g., as described with respect to device 101. Additionally, device 102 generally also includes terminals 10 and 11, via which electrodes 8 and 9, respectively, may be electrically connected to the controller. For example, as shown, wires extending from the controller may be connected to the terminals. The wires may be electrically insulated from one another.

[0183] For some applications, bioimpedance sensing may be performed by one or more bioimpedance sensing electrodes that apply a current to tissue (e.g., between two electrodes) and measure the resulting current. For some applications, the controller 2010 is adapted to drive the bioimpedance sensing, for example, by providing the current used to perform the bioimpedance sensing. For some applications, the generator 7a is used to provide this current, for example, via terminals 10 and 11.

[0184] For some applications, bioimpedance sensing is performed in a constant potential mode. For some applications, bioimpedance sensing is performed in a constant current mode. For some applications, the current used to perform bioimpedance sensing is a low voltage current (e.g., at least 0.5 V and / or 5 V or less). For some applications, the current used to perform bioimpedance sensing has a sinusoidal waveform. For some applications, the current used to perform bioimpedance sensing has a frequency of at least 10 Hz and / or 1 MHz or less. For some applications, the current used to perform bioimpedance sensing has an amplitude of at least 1 microampere and / or 15 milliamperes or less.

[0185] Once the distal region 200 has been advanced to the tumor 15, the tumor's boundaries may be determined using the bioimpedance sensing electrodes 8 and 9. For example, as described above, due to differences in tissue properties between a tumor and its surrounding tissue, the device (e.g., its control device 2010) may determine (or facilitate the determination of) the tumor's boundaries by moving (or facilitating the movement of) the bioimpedance sensing electrodes 8 and 9 relative to the tumor and sensing bioimpedance at different locations. For example, as shown schematically in FIGS. 6A-D, the bioimpedance sensing electrodes may be advanced into and / or out of the tumor so that the precise location of the transition (i.e., boundary) between the inside and outside can be identified—e.g., by determining whether each of the bioimpedance sensing electrodes 8 and 9 is positioned inside or outside the tumor.

[0186] For some applications, this determination is accomplished by sensing the bioimpedance between the bioimpedance sensing electrodes 8 and 9 (e.g., the bioimpedance sensing electrodes are used in a bipolar fashion). For some applications, a remote electrode 40, such as a skin electrode or a grounding pad, is used. For example, a determination of whether the bioimpedance sensing electrode 8 is inside or outside the tumor 15 may be facilitated (or made) by sensing the bioimpedance between the bioimpedance sensing electrode 8 and the remote electrode 40, and a similar determination may be made for the bioimpedance sensing electrode 9 (e.g., each of the bioimpedance sensing electrodes 8 and 9 is used in a monopolar fashion), with the controller 2010 being able to verify the position of each of the bioimpedance sensing electrodes independently of the other. For some applications, a combination of bipolar and unipolar sensing is implemented. For some applications, electrode 8 or electrode 9 may be replaced by a skin electrode or a grounding pad.

[0187] For some applications, the bioimpedance between each bioimpedance sensing electrode and its respective electroporation electrode may be determined. For example, the bioimpedance between bioimpedance sensing electrode 8 and electroporation electrode 2 may be detected to determine whether electroporation electrode 2 is within the boundaries of a tumor. Additionally or alternatively, the bioimpedance between bioimpedance sensing element 9 and electroporation electrode 4 may be detected to determine whether electroporation electrode 4 is within the boundaries of a tumor.

[0188] For some applications, bioimpedance sensing is performed between a combination of bioimpedance sensing electrodes, electroporation electrodes, and / or remote electrodes, e.g., using two, three, or more (e.g., four) of electrodes 2, 4, 8, 9, and 40 to perform bioimpedance sensing. For some applications, two or more sensing electrodes may be used proximal and / or distal to the electroporation electrodes. For example, there may be a pair of bioimpedance sensing electrodes positioned proximal to electrode 2 and / or a pair of bioimpedance sensing electrodes positioned distal to electrode 2, and bioimpedance may be sensed between the proximal pair of electrodes and / or the distal pair of electrodes. Similarly, there may be a pair of bioimpedance sensing electrodes positioned proximal to electrode 4 and / or a pair of bioimpedance sensing electrodes positioned distal to electrode 4, and bioimpedance may be sensed between the proximal pair of electrodes and / or the distal pair of electrodes. In some embodiments, bioimpedance is measured between the most distal bioimpedance sensing electrode and the most proximal bioimpedance sensing electrode.

[0189] For some applications, a remote electrode (e.g., remote electrode 40 or the like, e.g., a skin electrode) may be used to facilitate delivery of the electroporation pulse to the tumor—e.g., with the remote electrode functioning as a return electrode. For example, the pulse may be delivered via electrode 4, electrode 2, or both electrodes 4 and 2 may cooperate to function as a single electrode. For example, electrode 2 or electrode 4 may be replaced with a skin electrode or ground pad. This may be considered a "monopolar" configuration, while application of the pulse between electrodes 2 and 4 may be considered a "bipolar" configuration. For some applications, a single tumor may be treated with a combination of both monopolar and bipolar pulses.

[0190] For some applications, the controller 2010 is adapted to provide an output, e.g., a visual output via a screen, and / or an audible output and / or a tactile or haptic output, in response to bioimpedance sensing performed by one or more bioimpedance sensing electrodes. For example, a representation of the tumor boundary (e.g., a map showing the tumor boundary) may be output by the controller to enable the surgeon to position one or more electroporation electrodes within the boundary. For some applications, the output is discrete, e.g., a text output indicating the tissue type that is determined to be the location of the bioimpedance sensing electrode (and / or electroporation electrode).

[0191] Device 102 is configured such that the position of its therapeutic applicator (e.g., electrodes 2 and 4) is in a fixed and / or known position relative to its bioimpedance sensing electrodes 8 and 9, automatically positioning (or facilitating positioning) the therapeutic applicator just inside the tumor boundary by positioning electrodes 8 and 9 just outside the tumor boundary. For example, as shown in Figures 2 and 6A-D, by virtue of an arrangement in which electroporation electrodes 2 and 4 are positioned axially between bioimpedance sensing electrodes 8 and 9, establishing that the bioimpedance sensing electrodes are at (e.g., just outside) the boundary of tumor 15 can automatically demonstrate that electroporation electrodes 2 and 4 are just inside the boundary—e.g., within 5 mm or less (e.g., 4 mm or less, e.g., 3 mm or less, e.g., 2 mm or less) and / or at least 0.5 mm (e.g., at least 1 mm, e.g., at least 2 mm, e.g., at least 3 mm), e.g., within 0.5-5 mm of the boundary. For some applications, a similar technique can be used so that, rather than positioning electrodes 8 and 9 just outside the boundary of tumor 15, they are positioned just inside the boundary.

[0192] For some applications, and as shown, distal region 200 may include a nested assembly—e.g., having distal portion 24 (which may be the distal portion of shaft 3) and proximal portion 22 (which may be the distal portion of shaft 1) that are axially slidable relative to one another. For some applications, shafts 1 and 3 are coaxial. For some such applications, electroporation electrode 4 is positioned on distal portion 24, and bioimpedance sensing electrode 9 is positioned on the distal portion just distal to electroporation electrode 4—e.g., more than 0.5 mm (e.g., more than 1 mm) and / or less than 10 mm (e.g., less than 5 mm) distal—such that positioning bioimpedance sensing electrode 9 just beyond the tumor boundary positions electroporation electrode 4 just within the boundary. That is, electrode 4 is positioned on the opposite side of the boundary from electrode 9, with the boundary being between the electrodes. Thus, the bioimpedance sensing electrode 9 can be used by the controller 2010 to detect the distal boundary and provide an alert (e.g., a visual, audible, tactile, and / or haptic alert), for example, indicating that further distal advancement is not needed (or desired). Similarly, the second electrode 2 is positioned in the proximal portion 22, and the bioimpedance sensing electrode 8 is positioned in the proximal portion just proximal—e.g., more than 0.5 mm (e.g., more than 1 mm) and / or less than 5 mm (e.g., less than 10 mm) proximal—from the electroporation electrode 2, such that positioning of the bioimpedance sensing electrode 8 just before (e.g., proximally from) the tumor boundary positions the electroporation electrode 2 just within the boundary.

[0193] 6A-D may represent a series of steps that may be performed by a surgeon to position electroporation electrodes 2 and 4 at opposite borders of tumor 15. These steps are generally facilitated by bioimpedance sensing electrodes 8 and 9, which indicate the position of electroporation electrodes 2 and 4 relative to tumor 15, as described below. Note that FIGS. 6A-D are intended primarily to illustrate the capabilities of system 2000, rather than strictly defining the sequence of steps of the procedure.

[0194] The distal region 200 is first advanced into the tumor 15 so that the bioimpedance sensing electrode 9 and the electroporation electrode 4 enter the tumor (FIG. 6A). Placement of the electrode 9 within the tumor can be determined by bioimpedance sensing.

[0195] The distal region 200 continues to be advanced into the tumor 15 until the bioimpedance sensing electrode 9 exits the tumor—e.g., the distal boundary of the tumor (FIG. 6B). For example, the controller 2010 may provide an alert to the surgeon in response to a change in bioimpedance detected by the electrode 9 as the electrode exits the tumor 15. As explained above, this positioning of the bioimpedance sensing electrode 9 just outside the tumor boundary positions the electroporation electrode 4 just inside the boundary. In the particular example shown, while the distal region 200 is advanced into the tumor 15, the distance between electrodes 4 and 2 (i.e., the distance L described above) is sufficiently short so that the positioning of electrode 4 just inside the tumor's distal boundary positions both the electroporation electrode 2 and the bioimpedance sensing electrode 8 within the tumor (FIG. 6B). However, it will be understood that this will depend on the particular application of the device 102 and the size of the particular tumor.

[0196] 6C shows that electrodes 2 and 8 are moved proximally by axially extending the length of distal region 200 (e.g., telescoping proximal portion 22 of the distal region out from distal portion 24), positioning electrode 2 just inside the proximal boundary of the tumor. Similar to what was described with respect to distal electrode 9, controller 2010 may provide an alert to the surgeon in response to a change in bioimpedance detected by electrode 8 as the electrode exits tumor 15. As described above, this positioning of bioimpedance sensing electrode 8 just outside the tumor boundary positions electroporation electrode 2 just inside the boundary.

[0197] In this position, an electroporation pulse is then applied to the tumor, as represented by the electric field lines in Figure 6D.

[0198] For some applications, the controller 2010 is adapted to adjust the electroporation pulses applied by the generator 7 a in response to bioimpedance sensing. For example, the controller 2010 may be adapted to monitor the progress of treatment by monitoring changes in tumor impedance using the bioimpedance sensing electrodes 8 and 9. For some applications, this monitoring is performed repeatedly and / or continuously throughout the ablation process.

[0199] For some applications, bioimpedance sensing is also performed during and / or after the ablation process to optimize results.

[0200] For some applications, the electroporation pulse is applied while one or more bioimpedance sensing electrodes are just inside the boundary of the tumor, rather than while positioned just outside the boundary.

[0201] For some applications, following application of the initial electroporation pulse to tumor 15, electrodes 2 and 4 may be moved within the tumor and a second electroporation pulse may be applied to ensure adequate coverage of the tumor. For example, electrode 4 may be pulled back toward electrode 2, e.g., by telescopingly shortening distal region 200 by pulling distal portion 24 proximally. Alternatively or additionally, electrode 2 may be pushed forward toward electrode 4, e.g., by pushing proximal region 22 distally. In some embodiments, after application of the initial electroporation pulse, both electrodes may be removed and reinserted at a different angle or from a different entry point. In some embodiments, one electrode may be left in place and the other electrode inserted at a different angle.

[0202] In some embodiments, multiple shafts (e.g., multiple instances of shafts 3), each having an electroporation electrode, can be passed (e.g., simultaneously) through shaft 1. For some applications, each shaft 3 has a bioimpedance sensing electrode attached thereto to provide information regarding its respective electroporation electrode relative to the tumor boundary, e.g., as described above with respect to Figures 2 and 6A-D. For some applications, each of these shafts 3 is oriented at a different angle within the tumor to ensure complete coverage.

[0203] Reference may now be made to FIG. 3 , which shows a schematic diagram of device 103, according to some applications. Device 103 may be considered a variation of device 101 and / or device 102; for example, device 103 may be part of a system, such as system 2000, and / or may be compatible with a controller, such as controller 2010. Similar to the devices described above, device 103 has a distal region 300 adapted to be advanced into a tumor. Distal region 300 defines a proximal portion 32 and a distal portion 34, the distal portion being telescopically extendable relative to the proximal portion. Similar to the devices described above, first electroporation electrode 4 is disposed in the distal portion, and second electroporation electrode 2 is disposed in the proximal portion. As described with reference to device 102 above, bioimpedance sensing electrodes may be disposed in each of the distal and proximal portions, respectively.

[0204] 3, distal portion 34 is curved (or can be actively bent) relative to proximal portion 32, allowing electrode 4 to be oriented at an angle within the tumor relative to electrode 2. This may advantageously allow electrodes 2 and 4 to be positioned on opposite or suitably spaced borders of the tumor, allowing for complete eradication of the tumor.

[0205] Reference will now be made to FIG. 5, which is a schematic illustration of a tumor ablation device 104 in accordance with some embodiments of the present disclosure. Device 104 may be considered a variation of devices 101 and / or 102 and / or 103 and has a distal region 400 adapted to be advanced into a tumor. Distal region 400 defines a proximal portion 422 and a distal portion 424, the distal portion being telescopically extendable relative to the proximal portion. Similar to the devices described above, a first electroporation electrode 404 is disposed in the distal portion, and a second electroporation electrode 402 is disposed in the proximal portion. Bioimpedance sensing electrodes may be disposed in each of the distal and proximal portions, respectively, as described with reference to device 102 above. Also, similar to the above-described devices, device 104 includes shaft 401 through which shaft 403 can pass, such that in distal region 400 shaft 403 forms distal portion 424 and shaft 401 forms proximal portion 422.

[0206] The device 104 may be similar to those described above, except that the shaft 401 may define a side port through which the shaft 403 may be passed and the electrode 404 may be positioned at a selected border of the tumor. The distal end of the hollow shaft 401 may be closed or open. In some embodiments, the shaft 401 includes two or more side ports through which either multiple shafts 403 may be passed or the same shaft 403 may be selectively passed, allowing the electrode 404 to be positioned at various borders of the tumor. This may advantageously allow the positioning of the electrodes 402 and 404 at opposite or suitably spaced borders of the tumor, allowing for complete eradication of the tumor.

[0207] Reference is now made to Figures 7, 8, and 9A-B, which are schematic illustrations of devices that facilitate the placement of two or more distal regions (e.g., two or more therapeutic applicators) within a tumor, in accordance with some applications.

[0208] For some applications, a device having two or more distal regions is advanced into a tumor, with at least one therapeutic applicator and / or electroporation electrode disposed in each distal region of the device. For some applications, each distal region also includes a bioimpedance sensing electrode disposed therein to determine, for example, whether the electroporation electrode in that distal region is located within the tumor but at the tumor's borders. Having two or more distal regions can advantageously allow for positioning of electroporation electrodes at various borders of the tumor, ensuring complete coverage of the tumor's extent. For example, Figures 7-9B can be seen as devices having two or more distal regions for positioning electroporation electrodes.

[0209] 7 shows a system 7000 including multiple devices 102 advanced into a tumor 15, each device having at least one electroporation electrode disposed thereon. Each of the devices 102 can be considered to be a variation of or substantially identical to device 102 as described with reference to FIGS. 2 and 6A-D.

[0210] 8 shows a system 8000 including the device 108. The system 8000 may otherwise be identical to the system 7000, except that the device 108 may branch into two separate distal regions, as shown. This may allow access of the tumor via different access or entry points, and electrodes may be conveniently placed on different opposing borders of the tumor.

[0211] 9A shows an instrument 109 having a sheath (e.g., bronchoscope) 17 from which one or more shafts (e.g., steerable catheters) 18 can be advanced to direct distal regions 19, each with an electroporation electrode 20 positioned therein, into a tumor 15 from various access points or particular angles or points of interest. Each steerable catheter 18 can be advanced into the tumor from a different airway (e.g., bronchus) so that opposite and / or spaced boundaries of the tumor are accessed by each electrode 20. For some applications, bioimpedance sensing between the electroporation electrodes 20 is further performed to position the electrodes at the tumor boundaries.

[0212] For some applications, as shown in FIG. 9B , an otherwise identical device 109′ has a bioimpedance sensing electrode 26 positioned at each distal region 19 to provide information regarding the location of each respective electroporation electrode 20 prior to application of an electroporation pulse. For example, each bioimpedance sensing electrode 26 may be positioned proximally relative to the electroporation electrode 20 positioned at its distal region 19, and identifying that the bioimpedance sensing electrode 26 is positioned just outside the tumor 15 provides confirmation that the electrode 20 is just within the tumor boundary—e.g., as described above, mutatis mutandis.

[0213] Reference will now be made to FIGS. 10 and 11A-C, which are schematic illustrations of device 105 according to some applications. Device 105 may be considered a variation of any of the devices described above and may be part of a system, e.g., system 2000, and / or may be compatible with a controller, e.g., controller 2010. Like the devices described above, device 105 has a distal region 500 adapted to be advanced into a tumor. Unlike the devices described above, device 105 may include a single electroporation electrode 21, generally flanked by a distal bioimpedance sensing electrode 28 and a proximal bioimpedance sensing electrode 29. A remote electrode (e.g., remote electrode 40 or the like, e.g., a skin electrode) may be used to facilitate delivery of the electroporation pulse to the tumor—e.g., with the remote electrode functioning as a return electrode.

[0214] For some applications, bioimpedance sensing electrodes 28 and 29 are positioned on the side of the electroporation electrode 21, allowing the bioimpedance sensing electrodes to be used by the control device to detect the distal and / or proximal boundaries of the tumor and provide an alert, for example, to indicate that further distal or proximal advancement is not required (or desired).

[0215] 11A-C, the distal region 500 can be advanced into the tumor 15 until the bioimpedance sensing electrode 29 exits the tumor—e.g., the distal border of the tumor (FIG. 11A). For example, the controller can provide an alert to the surgeon in response to a change in bioimpedance detected by the electrode 29 as the electrode exits the tumor 15. As described above in connection with FIGS. 6A-D, this positioning of the bioimpedance sensing electrode 29 just outside the tumor border positions the electroporation electrode 21 just inside the border. While the electroporation electrode 21 is positioned at the border, electroporation pulses can be applied to the tumor to ablate at least a peripheral portion of the tumor.

[0216] 11B shows the distal region 500 being moved partway through the tumor (e.g., by withdrawing the distal region proximally). As the distal region is moving through the tumor, additional electroporation pulses can be applied to completely eradicate the tumor.

[0217] Bioimpedance sensing electrodes 28 can be used to detect the tumor border and to alert the surgeon once the electroporation electrode reaches the opposite border (e.g., the proximal border) of the tumor (FIG. 11C), which can signal that electroporation of the tumor is complete.

[0218] Reference will now be made to FIG. 12, which illustrates device 106 according to some applications. Device 106 may be considered a variation of device 105 and may be part of a system, e.g., system 2000, and / or may be compatible with a controller, e.g., controller 2010. Like device 105, device 106 has a distal region 600 adapted to be advanced into a tumor. However, as shown in FIG. 12, device 106 includes multiple (e.g., two) electroporation electrodes 21, such that, in some embodiments, electroporation pulses may be applied between the electroporation electrodes in a bipolar mode.

[0219] For some applications, bioimpedance sensing electrodes 28 and 29 are positioned at the distal and proximal ends of distal region 600 to identify tumor boundaries, as described above. For some applications, additional bioimpedance sensing electrodes 30 are positioned between electroporation electrodes 21. Bioimpedance can be sensed between any combination of electrodes 28, 29, 30, and a remote electrode, such as electrode 40.

[0220] Reference will now be made to Figures 13A-C, which are schematic diagrams of device 113 according to some applications.

[0221] Device 113 may be considered a variation of any of the devices described above and may be part of a system, e.g., system 2000, and / or may be compatible with a controller, e.g., controller 2010. Similar to the devices described above, device 113 has a distal region 700 adapted to be advanced into a tumor. Device 113 includes electroporation electrode 44 in the distal region—e.g., may include only a single electroporation electrode. Device 113 is configured to facilitate adjustment of the effective length of electroporation electrode 44—e.g., according to the size of the tumor. A remote electrode (e.g., remote electrode 40 or the like, e.g., a skin electrode or grounding pad) may be used to facilitate delivery of the electroporation pulse to the tumor—e.g., with the remote electrode functioning as a return electrode.

[0222] For some such applications, distal region 700 includes a telescoping assembly—e.g., having a distal portion 724 and a proximal portion 722 that are axially slidable relative to one another. For some such applications, instrument 113 includes an outer shaft 701 and an inner shaft 703 that is adapted to slide into and / or out of the distal end of shaft 701. Shafts 701 and 703 may be coaxial. For some such applications, and as described above with reference to instruments 101 and 102, the distal region of shaft 703 functions as distal portion 724, and the distal region of shaft 701 functions as proximal portion 722.

[0223] For some applications, shaft 701 controls the effective length of electroporation electrode 44 (i.e., the length of the electroporation electrode exposed in tissue) by insulating a portion of the electroporation electrode from tissue. For such applications, shaft 701 (or at least the portion of the shaft that serves as proximal portion 722) is generally electrically insulating—e.g., formed from or coated with a material that is an electrical insulator. For example, for some applications, electroporation electrode 44 is disposed on shaft 703, and extending shaft 701 proximally relative to shaft 703 increases the effective length of the electroporation electrode by exposing more of the electroporation electrode, and advancing shaft 701 distally over shaft 703 decreases the effective length of the electroporation electrode by covering, and therefore insulating, more of the electroporation electrode.

[0224] For some applications, a first bioimpedance sensing electrode 8 is positioned on the proximal portion 722, e.g., at the distal end of shaft 701, and a second bioimpedance sensing electrode 9 is positioned on the distal portion 724, e.g., distal to electrode 44. For such applications, such placement of the bioimpedance sensing electrodes near electroporation electrode 44 enables the bioimpedance sensing electrodes to be used by a controller to detect the distal and / or proximal boundaries of the tumor, e.g., to identify an appropriate length for distal region 700 and thereby an appropriate effective length for electrode 44—e.g., by providing an alert when the appropriate length is achieved. For some applications, and as shown, device 113 is configured so that, at the appropriate length, electroporation electrode 44 spans most of the length of the tumor (i.e., most of the distance between the distal boundary of the tumor and the proximal boundary of the tumor)—e.g., substantially the entire length of the tumor.

[0225] As shown by FIGS. 13A-C, distal region 700 can be advanced into tumor 15 until bioimpedance sensing electrode 9 exits the tumor—e.g., the tumor's distal boundary (FIG. 13A). For example, a controller can provide an alert to the surgeon in response to a change in bioimpedance detected by electrode 9 as the electrode exits tumor 15. Similar to what was described above in connection with FIGS. 6A-D, this positioning of bioimpedance sensing electrode 9 just outside the tumor boundary positions the distal end of electroporation electrode 44 just inside the boundary. In this state, electroporation electrode 44 may not yet have the desired effective length. Therefore, proximal portion 722 is then withdrawn proximally from distal portion 724 (e.g., by sliding shaft 701 proximally along shaft 703), thereby exposing more of electroporation electrode 44 within the tumor (FIG. 13B). In the illustrated example, the proximal portion 722 is withdrawn until the bioimpedance sensing electrode 8 exits the tumor, and the electroporation electrode 44 has a desired effective length—e.g., spanning substantially the entire length of the tumor (FIG. 13C). In this state, the electroporation electrode 44 can then be driven (e.g., by generator 7a or the like) to apply an electroporation pulse to the tumor.

[0226] For some applications, device 113 is adjustable to allow the effective length of electroporation electrode 44 to be at least 1 mm and / or up to 50 mm.

[0227] Reference is now made to FIG. 4, which shows a schematic cross section through the shaft 1 according to some applications.

[0228] In some embodiments, hollow shaft 1 can be constructed in the form of a braided shaft, where outer jacket 212 and inner liner 214 are biocompatible polymers (e.g., Pebax, silicone, polyurethane, polyethylene, and / or Teflon). Braid 13 is preferably metallic (e.g., tungsten or stainless steel wire can be used). One or more of the braided wires can function as conductors electrically connecting electrode 2 and / or electrode 8 to their respective terminals. The inner diameter of hollow shaft 1 is generally at least 0.25 mm, e.g., at least 0.35 mm. The outer diameter is generally less than 5 mm, e.g., less than 2 mm. The use of a flexible structure, such as a braid, is advantageous because it allows for delivery of the device through complex anatomical structures. An example of this could be the intrabronchial insertion of a device for treating a lung tumor.

[0229] In some embodiments, hollow shaft 1 is constructed of an additional layer of braid and polymer tubing. Advantageously, the additional layer can be used to transmit signals from bioimpedance sensing electrodes 8. For example, braid 13 can function as a conductor for electrode 2, while the additional layer of braid can function as a conductor for electrode 8.

[0230] In some embodiments, the braid may be replaced with multiple wires that are electrically insulated from one another.

[0231] In some embodiments, any of the braids may be replaced with hypotubes, which may be laser cut to increase flexibility, and in other embodiments, any of the braids may be replaced with coils or wires.

[0232] In some embodiments, shaft 3 may be constructed in a similar manner to hollow shaft 1, mutatis mutandis.

[0233] In some embodiments, the shaft 3 can be configured to include an inner lumen that can have a distal opening. In other embodiments, the distal end can be closed—for example, as shown. The outer diameter of the shaft 3 is generally less than 2 mm, for example, less than 1 mm.

[0234] In some embodiments, the shaft 3 may be constructed from an insulating tube through which electrical signals are passed from the proximal terminal to the electrodes using conductive wires. In some embodiments, the shaft may be constructed from a metallic tube or tubes partially covered with an insulating layer or layers.

[0235] In some embodiments, the signal from the bioimpedance sensing electrode is delivered in a manner similar to that described for driving one or more pulses to the electroporation electrodes, for example, an additional layer of braid, coil, or tube may be included that insulates the electroporation electrodes and their wiring.

[0236] 1-13C, for some applications, the same electrodes used for bioimpedance sensing are also used for electroporation - for example, for such applications, electrodes 2 and 4 shown in FIG. 1 may also be used to provide information about the bioimpedance sensed at the tumor to the controller 1010 in order to provide the controller with information about the positioning of the electrodes relative to the tumor.

[0237] Although electroporation electrodes are mentioned throughout this application, it is understood that for some applications, other types of therapeutic applicators may be used. A non-limiting list of possible therapeutic applicators includes RF electrodes, radiation (e.g., microwave, laser) applicators, high-intensity focused ultrasound transducers, or dispensers for drugs (e.g., chemotherapy agents), caustics (e.g., ethanol), cryogenic fluids, or radiation sources. For some applications, such other therapeutic applicators are used in place of the electroporation electrodes. For some applications, such other therapies are used in combination with the electroporation electrodes—e.g., to produce a synergistic effect. For some such applications, the therapeutic applicators for such additional therapies are coupled to and / or advanced through the outer shaft of the device. For other such applications, the therapeutic applicators for such additional therapies are coupled to and / or advanced through the inner shaft of the device.

[0238] In some embodiments, the electroporation and / or bioimpedance sensing electrodes may be constructed from biocompatible metals (eg, platinum, iridium, gold, tungsten, stainless steel, titanium).

[0239] In some embodiments, the electroporation and / or bioimpedance sensing electrodes may be in the form of a coil, braid, mesh, ring, or laser cut tube.

[0240] In some embodiments, any of the bio-impedance sensing elements may be in the form of a ring, a wire, or a printed circuit.

[0241] In some embodiments, the length of each electroporation electrode can be at least 1 mm (eg, at least 2 mm) and / or 50 mm or less (eg, 20 mm or less, eg, 10 mm or less).

[0242] In some embodiments, the length of each bioimpedance sensing electrode may be at least 1 mm (eg, at least 2 mm) and / or 50 mm or less (eg, 20 mm or less, such as 10 mm or less, such as 5 mm or less).

[0243] In some embodiments, the different electroporation electrodes have different shapes or sizes to achieve optimal field distribution, for example, one may be longer than the other.

[0244] In some embodiments, the diameter of electrode 4 may be at least 0.25 mm (eg, at least 0.35 mm) and / or 2 mm or less (eg, 1 mm or less).

[0245] In some embodiments, the diameter of electrode 2 may be at least 0.35 mm (eg, at least 0.5 mm) and / or 4 mm or less (eg, 2 mm or less).

[0246] The distance L, defined as the distance between the proximal end of the inner electrode 4 and the distal end of the outer electrode 2, may be adjustable to allow for target tissue coverage and optimal energy distribution. In some embodiments, the device is configured such that the maximum value of L is at least 5 mm, e.g., at least 20 mm.

[0247] In some embodiments, the generator 7 is configured to apply the high voltage pulses required for electroporation. For example, the duration of each pulse may be at least 0.1 microseconds (e.g., at least 0.5 microseconds, e.g., at least 1 microsecond, e.g., at least 2 microseconds) and / or 1 second or less—e.g., 1 millisecond or less, e.g., 0.5 milliseconds or less, e.g., 100 microseconds or less, e.g., 10 microseconds or less, e.g., 2 microseconds or less (e.g., 0.1-100 microseconds). The pulses may be spaced apart in time by at least 0.1 microseconds (e.g., at least 1 microsecond) and / or 1 millisecond or less, e.g., 0.5 milliseconds or less, e.g., 100 microseconds or less, e.g., 10 microseconds or less, e.g., 2 microseconds or less (e.g., 0.1-10 microseconds).

[0248] The frequency of the current of each pulse may be 1-5 MHz, e.g., 1-3 MHz, e.g., 1-2.5 MHz. The voltage of the current used may be sufficient to induce either reversible or irreversible electroporation. For some applications, the voltage of each pulse is at least 200 V (e.g., at least 500 V, e.g., at least 2000 V) and / or 1000 V or less (e.g., 500 V or less)—e.g., 200-500 V. In some embodiments, the polarity of the voltage may alternate between positive and negative polarity (e.g., bipolar mode), or alternatively, the voltage may not alternate polarity (e.g., monopolar mode).

[0249] For some applications, the pulses may be applied in multiple pulse trains with rest periods between them (where the pulses may have the characteristics and spacing described below). For some applications, each train consists of at least 100 pulses (e.g., at least 1,000 pulses) and / or up to 1 million pulses (e.g., up to 100,000 pulses, e.g., up to 10,000 pulses, e.g., up to 1,000 pulses). For some applications, rest periods of at least 100 milliseconds (e.g., at least 500 milliseconds, e.g., at least 1 second) and / or less than 1 minute (e.g., less than 10 seconds, e.g., less than 5 seconds) are provided between pulse trains.

[0250] Alternatively, the generator may be used to drive one or more of the electrodes of the device to apply RF energy for RF ablation—for example, using an alternating current of 300-600 kHz.

[0251] In some embodiments, a microwave antenna may be used in place of the electroporation electrodes, and the generator 7 may be a microwave generator.

[0252] In some embodiments, the electrodes are configured to be delivered percutaneously (e.g., transluminally). The effective length of such percutaneous devices, described as the length between the proximal terminal and the electrode, may be, for example, at least 10 cm and / or not more than 50 cm, e.g., between 15 cm and 50 cm.

[0253] In some embodiments, the electrode is configured for delivery through a bronchoscope. The effective length of the device, described as the length between the proximal terminal and the electrode, can be, for example, at least 40 cm, e.g., 60 cm to 150 cm. Endobronchial access has the advantage of reducing potential safety risks (e.g., pneumothorax).

[0254] In some embodiments, the electrodes are configured to be delivered through a sheath or catheter, and in such embodiments, the effective length of the device, described as the length between the proximal terminal and the electrode, may be, for example, at least 40 cm, such as between 60 cm and 180 cm.

[0255] In some embodiments, the bioimpedance sensing electrodes may also be used to evaluate the electric field generated during the ablation process. This may be of particular use when using electroporation for ablation. The measured electric field and impedance values ​​may be used to assess the ablation area or adjust the applied voltage accordingly.

[0256] In some embodiments, any of the shafts described herein may be used to perform a biopsy on a target site (e.g., a tumor)—e.g., guided by bioimpedance sensing. For example, one or more of the shafts described herein may be coupled to, configured to guide, and / or include a biopsy tool, e.g., a biopsy needle.

[0257] For some applications, bioimpedance sensing is performed as part of a diagnostic procedure. For some applications, bioimpedance sensing electrodes may be used to determine whether a lesion or growth is a cancerous tumor—e.g., to facilitate diagnosis. For example, the bioimpedance of a cancerous tumor may be different from the bioimpedance of a non-cancerous lesion or growth.

[0258] For some applications, the device may be used to perform biopsies in addition to using bioimpedance sensing to determine if a tumor is cancerous.

[0259] For some applications, by monitoring the bioimpedance measured by one or more bioimpedance sensing electrodes over a patient's respiratory cycle, it may be possible to determine whether one or more bioimpedance sensing electrodes (and therefore one or more electroporation electrodes) are positioned within a tumor. For example, the bioimpedance value of lung parenchyma may change (e.g., oscillate) during the respiratory cycle (e.g., impedance decreases during exhalation and increases during inhalation), whereas a tumor may have a more consistent bioimpedance value throughout the respiratory cycle. For some applications, receiving a signal with an oscillation magnitude above a threshold magnitude indicates that the tissue in which the bioimpedance sensing electrode is located is lung tissue (e.g., lung parenchyma) rather than tumor tissue.

[0260] For some applications, the frequency of vibrations sensed in the tumor by the bioimpedance sensing electrodes is compared to the frequency of the patient's respiratory cycle to ensure that the sensed vibrations reflect the respiratory cycle and do not arise from other factors (e.g., the patient's pulse). This may therefore provide the surgeon with further confirmation as to whether a particular tissue is a tumor and / or the location of one or more bioimpedance sensing electrodes relative to the tumor.

[0261] Therefore, according to some applications: receiving information indicative of the bioimpedance of tissue in the subject's lungs (optionally including information indicative of oscillations in the bioimpedance, e.g., amplitude and / or frequency of the oscillations); and In response, determining (e.g., diagnosing) whether the tissue is tumorous and / or cancerous. A method is provided which includes:

[0262] Tumor ablation is given as an example of one use of the device, but any of the above may also be used to induce electric fields to enhance drug uptake or to ablate other target tissues or sites.

[0263] Note that for some applications, any of the skin electrodes described herein may be replaced with a ground pad.

[0264] It should be noted that the electrodes described herein (e.g., bioimpedance sensing electrodes and electroporation electrodes) are shown as rings or tubes circumscribing their respective shafts, and the scope of this disclosure includes other shapes and configurations.

[0265] Those skilled in the art will recognize that the present disclosure is not limited to what has been particularly shown and described above, but rather, the scope of embodiments of the present disclosure includes both combinations and subcombinations of the various features described above, as well as variations and modifications thereof that would occur to one skilled in the art upon reading the above description and that are not in the prior art.

Claims

1. 1. An apparatus for ablating a tumor within a subject, the apparatus comprising: an instrument having a distal region; a bioimpedance sensing electrode in the distal region; a treatment applicator adapted to ablate tissue of the tumor and to be positionally fixed in the distal region relative to the bioimpedance sensing electrode; and a shaft to which the bioimpedance sensing electrode is attached, comprising: a first location where the bioimpedance sensing electrode is placed within the tumor; and a second position in which the bioimpedance sensing electrode is positioned outside the tumor and the treatment applicator is positioned within the tumor. A shaft that can be advanced to 1. An apparatus comprising:

2. The device of claim 1 , wherein in the first position of the shaft, the treatment applicator is positioned outside the tumor.

3. The device of claim 1 or 2, wherein the distal region defines a tissue piercing tip.

4. The device of any one of claims 1 to 3, wherein the distal region is bendable within the tumor.

5. 5. The device of claim 1, wherein the device is a first device and the device further comprises at least one additional device, each additional device having a distal region including a therapeutic applicator and a bioimpedance sensing electrode.

6. The device of any one of claims 1 to 5, wherein the therapeutic applicator is attached to the shaft proximally from the bioimpedance sensing electrode.

7. The device of any one of claims 1 to 6, wherein the therapeutic applicator is attached to the shaft distal to the bioimpedance sensing electrode.

8. The device of any one of claims 1 to 7, wherein the shaft is flexible.

9. The device of any one of claims 1 to 8, wherein the shaft is rigid.

10. the therapeutic applicator includes an electroporation electrode; the shaft is a first shaft, and the electroporation electrode is disposed on the first shaft; the instrument further includes a second shaft; and 10. The device of claim 1, wherein the first shaft and the second shaft are reversibly movable relative to one another by the first shaft being axially slidable relative to the second shaft.

11. the first shaft is an inner shaft; the second shaft is an outer shaft that is slidable over the inner shaft; and The device of claim 10 , wherein the instrument is configured such that the effective length of the electroporation electrode is adjustable by sliding the outer shaft over the electroporation electrode.

12. The device of claim 10 , wherein the bioimpedance sensing electrode is positioned on the first shaft distally from the electroporation electrode.

13. 13. The apparatus of claim 12, wherein the device further comprises another bioimpedance sensing electrode disposed on the second shaft.

14. the tumor is located in the subject's lung; and The device according to any one of claims 1 to 13, wherein the device is configured to determine the boundaries of the lung tumor by sensing performed by the bioimpedance sensing electrodes.

15. 15. The device of claim 14, wherein the device comprises a bronchoscope transbronchially advanceable to the lung, the shaft being deliverable via the bronchoscope to the tumor.

16. The device of any one of claims 1 to 15, further comprising a remote electrode, and the device configured to sense bioimpedance between the remote electrode and the bioimpedance sensing electrode.

17. 17. The device of claim 16, wherein the remote electrode is a skin electrode.

18. The treatment applicator comprises: an electroporation electrode; and 18. The device of any one of claims 1 to 17, adapted to apply electroporation pulses to the tumor using the electroporation electrodes.

19. 20. The device of claim 18, wherein the device further comprises a remote electrode, and the device is configured to apply the electroporation pulse between the remote electrode and the electroporation electrode.

20. 20. The device of claim 18, wherein the device is configured to sense bioimpedance at the tumor by sensing bioimpedance between the electroporation electrode and the bioimpedance sensing electrode.

21. the electroporation electrode is a first electroporation electrode; the therapeutic applicator further includes a second electroporation electrode; and 20. The device of claim 18, wherein the device is configured to apply the electroporation pulse between the first electroporation electrode and the second electroporation electrode.

22. 22. The device of claim 21, wherein the first and second electroporation electrodes are attached to the distal region, and the distal region is reversibly lengthenable to vary the axial distance between the first electroporation electrode and the second electroporation electrode.

23. The distal region includes: a telescoping assembly, the telescoping assembly including: a distal portion having the first electroporation electrode disposed thereon; and a proximal portion on which the second electroporation electrode is disposed, the distal region being reversibly lengthenable by axially sliding the distal portion and the proximal portion relative to one another; 23. The apparatus of claim 22, comprising:

24. 24. The device of claim 23, wherein the bioimpedance sensing electrode is positioned on the distal portion distal to the first electroporation electrode.

25. 25. The apparatus of claim 24, wherein the device further comprises a second bioimpedance sensing electrode disposed in the proximal portion proximally from the second electroporation electrode.

26. the shaft is a first shaft, and the first electroporation electrode is disposed on the first shaft; the device further includes a second shaft, the second electroporation electrode being disposed on the second shaft; and 22. The device of claim 21, wherein the first shaft and the second shaft are reversibly movable relative to one another by the first shaft being slidable through the second shaft.

27. 27. The device of claim 26, wherein the first shaft and the second shaft diverge relative to one another at the distal region.

28. 28. The device of claim 27, wherein each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

29. 27. The device of claim 26, wherein the second shaft defines a side port through which the first shaft is advanceable.

30. 30. The device of claim 29, wherein the first shaft is bendable relative to the second shaft.

31. 27. The device of claim 26, wherein the first shaft is advanceable from a distal end of the second shaft.

32. 32. The apparatus of any preceding claim, wherein the apparatus includes a controller adapted to receive signals from the bio-impedance sensing electrodes and in response provide an output indicative of the bio-impedance of tissue adjacent the bio-impedance sensing electrodes.

33. 33. The apparatus of claim 32, wherein the controller is adapted to determine a change in the signal over at least a portion of a respiratory cycle of the subject, and the output is indicative of a change in bioimpedance of the tissue adjacent the bioimpedance sensing electrode over at least the portion of the respiratory cycle.

34. 33. The apparatus of claim 32, wherein the controller is configured to output information indicative of a position of the bioimpedance sensing electrodes relative to the tumor in response to the signal.

35. the device includes a terminal electrically connected to the bioimpedance sensing electrode via a conductor extending along the shaft; and 33. The device of claim 32, wherein the control device is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control device to the terminals.

36. the therapeutic applicator is configured to apply an electroporation pulse to the tumor; and 33. The device of claim 32, wherein the control device comprises a generator electrically connectable to the treatment applicator and adapted to drive the treatment applicator to apply the electroporation pulses.

37. 37. The device of any one of claims 1 to 36, wherein the therapeutic applicator is positionally fixed at a distance of 10 mm or less relative to the bioimpedance sensing electrode.

38. 38. The device of claim 37, wherein the therapeutic applicator is positionally fixed at a distance of 5 mm or less relative to the bioimpedance sensing electrode.

39. 1. An apparatus for ablating a tumor in a lung of a subject, the apparatus comprising: shaft; a bioimpedance sensing electrode attached to a distal region of the shaft; and an electroporation electrode attached to the distal region of the shaft a fixed distance from the bioimpedance sensing electrode, the distal region of the shaft being advanceable to a location within the lung, where: the electroporation electrode is positioned within the borders of the tumor; and an electroporation electrode, wherein the bioimpedance sensing electrode is positioned outside the boundary of the tumor; Including equipment 1. An apparatus comprising:

40. 40. The apparatus of claim 39, wherein the apparatus is configured to determine the boundaries of the lung tumor by sensing performed by the bioimpedance sensing electrodes.

41. 41. The apparatus of claim 39 or 40, wherein the apparatus comprises a bronchoscope transbronchially advanceable to the lung, the shaft being deliverable via the bronchoscope to the tumor.

42. 42. The device of any one of claims 39 to 41, wherein the distal region defines a tissue piercing tip.

43. 43. The device of any one of claims 39 to 42, wherein the distal region is bendable within the tumor.

44. 44. The device of any one of claims 39 to 43, wherein the electroporation electrode is attached to the shaft proximally from the bioimpedance sensing electrode.

45. 45. The device of any one of claims 39 to 44, wherein the electroporation electrode is attached to the shaft distal to the bioimpedance sensing electrode.

46. 46. ​​The device of any one of claims 39 to 45, wherein the shaft is flexible.

47. 47. The device of any one of claims 39 to 46, wherein the shaft is rigid.

48. 48. The apparatus of any one of claims 39 to 47, further comprising a remote electrode, and the apparatus configured to sense bioimpedance between the remote electrode and the bioimpedance sensing electrode.

49. 49. The device of claim 48, wherein the remote electrode is a skin electrode.

50. 50. The device of any one of claims 39 to 49, wherein the electroporation electrode is adapted to apply an electroporation pulse to the tumor.

51. 51. The device of claim 50, wherein the device further comprises a remote electrode, and the device is configured to apply the electroporation pulse between the electroporation electrode and the remote electrode.

52. 51. The device of claim 50, wherein the device is configured to sense bioimpedance at the tumor by sensing bioimpedance between the electroporation electrode and the bioimpedance sensing electrode.

53. the electroporation electrode is a first electroporation electrode; the device further comprises a second electroporation electrode; and 51. The device of claim 50, wherein the device is configured to apply the electroporation pulse between the first electroporation electrode and the second electroporation electrode.

54. the shaft is a first shaft, and the first electroporation electrode is disposed on the first shaft; the device further includes a second shaft, the second electroporation electrode being disposed on the second shaft; and 54. The device of claim 53, wherein the first shaft and the second shaft are reversibly movable relative to one another by the first shaft being slidable within the second shaft.

55. 55. The apparatus of claim 54, wherein the first shaft and the second shaft diverge relative to one another at a distal region of the instrument.

56. 56. The device of claim 55, wherein each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

57. 55. The device of claim 54, wherein the bioimpedance sensing electrode is positioned on the first shaft distal to the first electroporation electrode.

58. 58. The apparatus of claim 57, wherein the device further comprises a second bioimpedance sensing electrode disposed on the second shaft proximally from the second electroporation electrode.

59. 55. The device of claim 54, wherein the second shaft defines a side port through which the first shaft is advanceable.

60. 60. The device of claim 59, wherein the first shaft is bendable relative to the second shaft.

61. 55. The device of claim 54, wherein the first shaft is advanceable from a distal end of the second shaft.

62. 62. The apparatus of any one of claims 39 to 61, wherein the apparatus includes a controller adapted to receive signals from the bioimpedance sensing electrodes and in response to provide an output indicative of the bioimpedance of tissue adjacent the bioimpedance sensing electrodes.

63. 63. The apparatus of claim 62, wherein the control device is adapted to determine a change in the signal over at least a portion of a respiratory cycle of the subject, and the output is indicative of a change in bioimpedance of the tissue adjacent the bioimpedance sensing electrode over at least the portion of the respiratory cycle.

64. 63. The apparatus of claim 62, wherein the controller is configured to provide an output in response to the signal that is indicative of a position of the bioimpedance sensing electrode relative to the tumor.

65. the device includes a terminal electrically connected to the bioimpedance sensing electrode via a conductor extending along the shaft; and 63. The device of claim 62, wherein the control device is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control device to the terminals.

66. 66. The apparatus of claim 65, wherein the controller is adapted to provide an electrical current to generate the signal.

67. the electroporation electrode is configured to apply an electroporation pulse to the tumor; and 63. The device of claim 62, wherein the control device comprises a generator electrically connectable to the electroporation electrodes and adapted to drive the electroporation electrodes to apply the electroporation pulses.

68. 68. The apparatus of any one of claims 39 to 67, wherein the fixed distance is 10 mm or less.

69. 69. The apparatus of claim 68, wherein the fixed distance is 5 mm or less.

70. 70. The device of any one of claims 39 to 69, wherein the shaft is a first shaft and the device further comprises at least a second shaft, the second shaft having a distal region including an electroporation electrode and a bioimpedance sensing electrode.

71. the instrument is a first instrument, the first shaft is a shaft of the first instrument, and 71. The apparatus of claim 70, further comprising a second instrument, and wherein the second shaft is the shaft of the second instrument.

72. 1. A method for ablating a tumor in tissue of a subject, the tumor having a boundary, the method comprising: advancing a distal region of a tumor ablation device into said tissue, said distal region having an electrode attached thereto; sensing the bioimpedance of the tissue using the distal region of the device; and positioning the electrode within the boundary of the tumor in response to the sensed bioimpedance; and applying an electroporation pulse to the tumor using the electrode while the electrode remains within the boundary. A method comprising:

73. sensing the bioimpedance of the tissue comprises sensing a change in the bioimpedance of the tissue over at least a portion of a respiratory cycle of the subject; and 73. The method of claim 72, comprising positioning the electrode within the boundary of the tumor in response to the sensed change in the bioimpedance.

74. the electrode is disposed on a first shaft of the instrument; the instrument further includes a second shaft; and 74. The method of claim 72 or 73, further comprising axially sliding the first shaft relative to the second shaft subsequent to positioning the electrode within the boundary of the tumor.

75. the first shaft is an inner shaft; the second shaft is an outer shaft that is slidable over the inner shaft; and 75. The method of claim 74, wherein axially sliding the first shaft relative to the second shaft comprises axially sliding the outer shaft over the electrode mounted on the inner shaft to adjust an effective length of the electrode.

76. the electrode is an electroporation electrode; the distal region further includes a bioimpedance sensing electrode; Sensing the bioimpedance using the distal region of the device includes sensing the bioimpedance using the bioimpedance sensing electrodes; and 76. The method of any one of claims 72-75, wherein positioning the electroporation electrode within the boundary of the tumor comprises moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor.

77. Sensing the bioimpedance using the bioimpedance sensing electrode includes sensing the bioimpedance using the bioimpedance sensing electrode while the bioimpedance sensing electrode is electrically connected to a controller, the controller being configured to provide an alert in response to a change in bioimpedance detected by the bioimpedance sensing electrode upon exiting the bioimpedance sensing electrode from the tumor; and 77. The method of claim 76, wherein positioning the electrode within the boundary of the tumor comprises positioning the electrode within the boundary in response to the alert.

78. 77. The method of claim 76, wherein the bioimpedance sensing electrode is positioned distal to the electroporation electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor comprises moving the distal region of the device distally through the tumor until the bioimpedance sensing electrode exits a distal boundary of the tumor.

79. 77. The method of claim 76, wherein the bioimpedance sensing electrode is positioned proximally relative to the electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor comprises moving the distal region of the device proximally through the tumor until the bioimpedance sensing electrode exits a proximal boundary of the tumor.

80. the electrode is a first electrode attached to a first portion of the distal region; the distal region further includes a second electrode attached to a second portion of the distal region; the first portion and the second portion are operable such that the first electrode is movable relative to the second electrode; and 80. The method of any one of claims 72-79, wherein applying the electroporation pulse to the tumor using the electrodes comprises applying the electroporation pulse between the first electrode and the second electrode.

81. the first portion is a distal portion of a first shaft; the second portion is a distal portion of a second shaft; and 81. The method of claim 80, wherein positioning the electrode within the boundary of the tumor comprises positioning the electrode within the boundary of the tumor by sliding the first shaft through the second shaft.

82. 81. The method of claim 80, wherein sensing the bioimpedance of the tissue comprises sensing the bioimpedance of the tissue between the first portion and the second portion.

83. The method further comprises, following application of the electroporation pulse: repositioning the electrode within the tumor; and applying another electroporation pulse to the tumor using the electrode.

83. The method of any one of claims 72 to 82, comprising:

84. 84. The method of claim 83, further comprising sensing the bioimpedance of the tissue using the distal region of the device following repositioning the electrode within the tumor and prior to applying the other electroporation pulse.

85. 1. A device for use on a tumor, said device comprising: A first portion comprising: a first bioimpedance sensing electrode; a first electroporation electrode attached to a second bioimpedance sensing electrode relative to the first bioimpedance sensing electrode; a first portion comprising: A second portion comprising: a second bioimpedance sensing electrode; and a second electroporation electrode mounted in a fixed position relative to the second bioimpedance sensing electrode. and a second portion comprising: a tumor ablation device having a distal region comprising: The device, wherein the distal region is operable to vary the axial distance between the first portion and the second portion.

86. 86. The device of claim 85, wherein the first portion is a first portion of a distal region of a first shaft of the instrument, and the second portion is a second portion of a distal region of a second shaft of the instrument.

87. 87. The device of claim 86, wherein the first shaft and the second shaft diverge relative to one another at the distal region.

88. 88. The device of claim 87, wherein each of the first shaft and the second shaft is adapted to access the tumor from an independent tumor access site.

89. 87. The device of claim 86, wherein the distal region is operable to vary the axial distance between the first and second portions by allowing the first shaft to slide within the second shaft.

90. 90. The device of claim 89, wherein the first shaft is advanceable from a distal end of the second shaft.

91. 87. The device of claim 86, wherein the first bioimpedance sensing electrode is positioned on the first shaft distal to the first electroporation electrode.

92. 87. The device of claim 86, wherein the second bioimpedance sensing electrode is positioned on the second shaft proximally from the second electroporation electrode.

93. 87. The device of claim 86, wherein the first bioimpedance sensing electrode is positioned on the first shaft proximally from the first electroporation electrode.

94. 87. The apparatus of claim 86, wherein the second shaft defines a side port through which the first shaft is advanceable.

95. 95. The device of claim 94, wherein the first shaft is bendable relative to the second shaft.

96. 1. An apparatus for ablating a tumor in a lung of a subject, the apparatus comprising: shaft; a bioimpedance sensing electrode attached to a distal region of the shaft; and an electroporation electrode attached to the distal region of the shaft a known distance from the bioimpedance sensing electrode, the distal region of the shaft advanceable to a location within the lung, wherein: the electroporation electrode is positioned within the borders of the tumor; and an electroporation electrode, wherein the bioimpedance sensing electrode is positioned outside the boundary of the tumor; Apparatus, including equipment including.

97. 1. A device for ablating a tumor, comprising: shaft; a first bioimpedance sensing electrode disposed in a distal region of the shaft; a second bioimpedance sensing electrode disposed in the distal region of the shaft; and an electroporation electrode disposed axially on the shaft between the first bioimpedance sensing electrode and the second bioimpedance sensing electrode; Apparatus, including equipment including.

98. 1. A method for ablating a tumor, comprising: advancing a distal region of a tumor ablation device into the tumor, the distal region having an electroporation electrode attached thereto and flanked by a proximal bioimpedance sensing electrode and a distal bioimpedance sensing electrode; determining a distal boundary of the tumor by sensing bioimpedance facilitated by the distal bioimpedance sensing electrode; in response to determining the distal boundary and while the electroporation electrode is positioned within the distal boundary, actuating the electroporation electrode to apply a first electroporation pulse to the tumor; determining the proximal boundary of the tumor by sensing bioimpedance facilitated by the proximal bioimpedance sensing electrode; and activating the electroporation electrode to apply a second electroporation pulse to the tumor in response to determining the proximal boundary and while the electroporation electrode is positioned within the proximal boundary. A method comprising:

99. 99. The method of claim 98, wherein driving the electroporation electrode to apply the first electroporation pulse to the tumor comprises driving the electroporation electrode to apply the first electroporation pulse to the tumor before applying the second electroporation pulse to the tumor.

100. 100. The method of claim 98 or 99, wherein driving the electroporation electrode to apply the first electroporation pulse to the tumor comprises driving the electroporation electrode to apply the first electroporation pulse to the tumor followed by applying the second electroporation pulse to the tumor.

101. 101. The method of any one of claims 98-100, further comprising applying a plurality of electroporation pulses to the tumor as the distal region of the device is advanced through the tumor.

102. 1. A method for use on the lungs of a subject, comprising: receiving information indicative of tissue bioimpedance oscillations within the lung; and In response, determining whether the tissue is tumor tissue. A method comprising:

103. Determining whether the tissue is tumor tissue comprises: determining whether the magnitude of the vibration is below a threshold magnitude; and determining that the tissue is tumor tissue in response to determining that the size is below the threshold.

103. The method of claim 102, comprising:

104. Determining whether the tissue is tumor tissue comprises: determining whether the magnitude of the vibration exceeds a threshold magnitude; and determining that the tissue is not tumorous tissue in response to determining that the size is above the threshold.

104. The method of claim 102 or 103, comprising:

105. 105. The method of claim 104, wherein determining whether the tissue is tumor tissue further comprises determining whether a frequency of the vibrations matches a frequency of vibrations of a respiratory cycle of the subject.

106. 1. A method for use on the lungs of a subject, comprising: receiving information indicative of the bioimpedance of tissue within the lung; and In response, determining whether the tissue is cancerous. A method comprising:

107. 1. An apparatus for use on a tumor within a subject, the apparatus including a tumor ablation device having a distal region, the device comprising: an inner shaft equipped with an electroporation electrode; and an outer shaft axially slidable over the inner shaft to facilitate adjustment of the effective length of the electroporation electrode, said adjustment being accomplished by: Distal advancement of the outer shaft over the inner shaft progressively covers the electroporation electrode, thereby progressively shortening the effective length of the electroporation electrode; and The proximal extension of the outer shaft above the inner shaft progressively exposes the electroporation electrode, thereby progressively increasing the effective length of the electroporation electrode.

1. An apparatus comprising:

108. 108. The device of claim 107, wherein the outer shaft is formed from an electrical insulator.

109. the electroporation electrode is configured to apply an electroporation pulse to the tumor; and The device of claim 107 or 108, further comprising a control device including a generator electrically connectable to the electroporation electrode and adapted to drive the electroporation electrode to apply the electroporation pulse.

110. 110. Apparatus according to any one of claims 107 to 109, wherein the device includes a bioimpedance sensing electrode attached to the distal region.

111. the bioimpedance sensing electrode is a first bioimpedance sensing electrode; the first bioimpedance sensing electrode is attached to the inner shaft distal to the electroporation electrode; and 111. The device of claim 110, wherein a second bioimpedance sensing electrode is attached to the outer shaft.

112. 111. The device of claim 110, wherein the device includes a controller adapted to receive signals from the bioimpedance sensing electrodes and, in response, to provide an output indicative of the bioimpedance of tissue adjacent the bioimpedance sensing electrodes.

113. 113. The apparatus of claim 112, wherein the control device is adapted to determine changes in the signal over at least a portion of a respiratory cycle of the subject, and the output is indicative of changes in bioimpedance of the tissue adjacent the bioimpedance sensing electrode over at least the portion of the respiratory cycle.

114. 113. The apparatus of claim 112, wherein the control device is configured to output information indicative of a position of the bioimpedance sensing electrode relative to the tumor in response to the signal.

115. the device includes a terminal electrically connected to the bioimpedance sensing electrode via a conductor; and 113. The device of claim 112, wherein the control device is electrically connectable to the bioimpedance sensing electrodes by electrically connecting the control device to the terminals.

116. 1. A method for ablating a tumor, comprising: advancing a distal region of a tumor ablation device into the tumor, the device comprising: an inner shaft equipped with an electroporation electrode; and an outer shaft adapted to slide over the inner shaft containing; positioning a distal end of the electroporation electrode within the tumor; adjusting the effective length of the electroporation electrode by sliding the outer shaft over the inner shaft; and activating the electroporation electrode to apply an electroporation pulse to the tumor; A method comprising:

117. 117. The method of claim 116, wherein adjusting the effective length of the electroporation electrode by sliding the outer shaft over the inner shaft comprises adjusting the effective length of the electroporation electrode until the electroporation electrode spans a desired percentage of the length of the tumor.

118. 118. The method of claim 117, wherein adjusting the effective length of the electroporation electrode until the electroporation electrode spans a desired length of the tumor comprises adjusting the effective length of the electroporation electrode until the electroporation electrode spans the entire length of the tumor.

119. the distal region further includes a bioimpedance sensing electrode; and A method according to any one of claims 116 to 118, wherein adjusting the effective length of the electroporation electrode comprises adjusting the effective length guided by sensing performed by the bioimpedance sensing electrode.

120. 120. The method of claim 119, wherein adjusting the effective length guided by sensing performed by the bioimpedance sensing electrodes comprises moving the distal region of the device through the tumor until the bioimpedance sensing electrodes exit the tumor.

121. 121. The method of claim 120, wherein the bioimpedance sensing electrode is electrically connected to a control device, and adjusting the effective length guided by sensing performed by the bioimpedance sensing electrode comprises adjusting the effective length until the control device provides an alert in response to a change in bioimpedance detected by the bioimpedance sensing electrode as it exits the tumor.

122. 121. The method of claim 120, wherein the bioimpedance sensing electrode is positioned on the inner shaft distal to the electroporation electrode, and moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor comprises moving the inner shaft distally through the tumor until the bioimpedance sensing electrode exits the distal boundary of the tumor.

123. the bioimpedance sensing electrode is a first bioimpedance sensing electrode; and the distal region further includes a second bioimpedance sensing electrode disposed on the outer shaft; and 121. The method of claim 120, wherein moving the distal region of the device through the tumor until the bioimpedance sensing electrode exits the tumor comprises moving the outer shaft proximally through the tumor until the second bioimpedance sensing electrode exits the proximal boundary of the tumor.

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